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Publications in the Health Sciences

Radiologic Diagnosis of Renal Transplant Complications

Publication of this book was assisted by a grant from the McKnight Foundation to the University of Minnesota Press's program in the health sciences.

Radiologic Diagnosis of Renal Transplant Complications W. R. Castaneda-Zuniga, Editor

University of Minnesota Press Minneapolis

Copyright ©1986 by the University of Minnesota. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Published by the University of Minnesota Press, 2037 University Avenue Southeast, Minneapolis MN 55414 Published simultaneously in Canada by Fitzhenry & Whiteside Limited, Markham. Printed in the United States of America Library of Congress Cataloging in Publication Data Main entry under title: Radiologic diagnosis of renal transplant complications. Includes index. 1. Kidneys—Transplantation —Complications and sequelae —Addresses, essays, lectures. 2. Diagnosis, Radioscopic —Addresses, essays, lectures. I. CastañedaZuñiga, Wilfrido R. [DNLM: 1. Kidney — transplantation. 2. Postoperative Complications—radiography. WJ 368 R129] RD575.R33 1985 617'.46101 85-2542 ISBN 0-8166-1232-3 The University of Minnesota is an equal-opportunity educator and employer.

Contents

Contributors

vii

Foreword John S. Najarian

ix

Introduction W. R. Castañeda-Zuñiga

xi

PART I. Diagnosis of Systemic Complications 1. Chest Film in the Assessment of Myocardial and Pericardial Abnormalities Luis Cueto-Garcia and W. R. Castañeda-Zuñiga 2.

3.

Echocardiography in Evaluating Effects on the Heart Luis Cueto-Garcia

11

Radiology of Pulmonary Complications David W. Hunter and Jeffrey Crass

20

4. Evaluation of Gastrointestinal Complications Math is P. Frick and Susan Roux 5.

3

Radiology of Skeletal and Soft Tissue Changes H. Charles Walker, Jr., Carol C. Coleman, and David W. Hunter

47

64

PART II. Diagnosis of Local Complications 6.

7.

Radiologic Evaluation of Urologic Complications Erich Salomonowitz and Marvin E. Goldberg

127

Nuclear Medicine as an Assessment Technique Merle K. Loken and Sal ma Mikhail

160

8. Angiographic Evaluation W. R. Castañeda-Zuñiga

201

9.

Use of Ultrasonography Ruth Rosenblatt and Rosalyn Kutcher

10. Evaluation by Digital Subtraction Angiography Antoinette S. Gomes

234

257

PART III. Therapeutic Techniques 11.

Interventional Radiology in the Management of Complications W. R. Castañeda-Zuñiga, David W. Hunter, and Kurt Amplatz

Index

265 301

Contributors

Antoinette S. Gomes, M.D. Department of Radiological

Sciences UCLA School of Medicine Los Angeles, California Kurt Amplatz, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota W. R. Castañeda-Zuñiga, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota Carol C. Coleman, M.D. Department of Radiology VA Medical Center Minneapolis, Minnesota Jeffrey Crass, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota Luis Cueto-Garcia, M.D. Echocardiography Lab Mayo Medical School Rochester, Minnesota MathisP. Frick, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota Marvin E. Goldberg, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota

David W. Hunter, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota Rosalyn Kutcher, M.D. Department of Radiology Montefiore Medical Center Albert Einstein College of Medicine Bronx, New York Merle K. Loken, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota Salma Mikhail, M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota Ruth Rosenblatt, M.D. Department of Radiology Montefiore Medical Center Albert Einstein College of Medicine Bronx, New York Susan Roux, M.D. Department of Radiology St. Joseph's Hospital St. Paul, Minnesota

Erich Salomonowitz, M.D. University of Vienna General Roentgen A-1090 Vienna, Austria H.Charles Walker, Jr., M.D. Department of Radiology Mayo Memorial Building University of Minnesota Minneapolis, Minnesota

Foreword

Renal transplantation has progressed to the stage where more than 4,500 transplants are being done annually in the United States and Europe. Because of this progress over the past 20 years, sophisticated techniques are being developed to help the clinician diagnose the causes of renal allograft dysfunction and thus begin appropriate early treatment. The major complications of renal transplantation relate either to dysfunction of the allograft itself or to a problem in the urinary conduit to the bladder. Infection in the region of the transplant and systemic infection also play an important role in the management of the renal transplant recipient. Because of the need for immunosuppressive drugs, the renal transplant patient also faces cardiopulmonary, gastrointestinal, orthopedic, and general infectious disease problems. This book summarizes the radiologic techniques available for the diagnosis of these problems. The techniques include the more sophisticated computerized axial tomography, as well as sonography, radionuclide imaging, and other invasive and noninvasive radiologic techniques. This volume is a welcome contribution to the literature and a useful manual for internists, surgeons, urologists, nephrologists, pediatricians, infectious disease physicians, and all other physicians involved in the care of the renal transplant patient. John S. Najarian, M.D. Professor and Chairman Department of Surgery University of Minnesota Hospitals

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Introduction

Renal transplantation has become the procedure of choice in the management of the patient with chronic renal insufficiency; consequently, thousands of kidney transplants are performed worldwide each year. Graft survival has increased slowly with the development of more powerful immunosuppressive drugs and with the more aggressive use of percutaneous renal biopsy procedures to detect and treat earlier rejection episodes. Most common graft failures occur within the first 1-3 months after the transplantation, and most of these failures are caused by rejection episodes. Cadaveric kidney transplants are especially susceptible to rejection. Differential diagnosis is sometimes difficult between rejection and the vascular and urologic problems that can mimic rejection. Technological advances have put new, less invasive tools in our hands to help in the diagnostic evaluation of these patients. We have seen the advent of dynamic nuclear medicine studies, ultrasonography, computed tomography, digital subtraction angiography, and the latest addition of nuclear magnetic resonance. The combination of these studies allows a more precise diagnostic evaluation of the different complications of renal transplantation, either related to rejection of the allograft itself or to problems in the vascular pedicle or the urinary conduit to the bladder. More invasive methods can be avoided in the diagnostic workup of these immunosuppressed patients. The evaluation of local and systemic complications of renal transplantations as described in the following pages is probably familiar to most readers because it has been reported in numerous scientific articles over the past 10-15 years. The information is so scattered, however, that the attending physician would need to conduct an extensive literature search to assemble it. In this work, we present a logical approach to the diagnostic evaluation of the different complications based on a full literature review and our own experience with more than 2,000 renal transplants. We hope that the book will provide an easy reference from which the diagnostic evaluation can start. Rather than attempting to include all possible systemic complications, we have limited ourselves to those that are

xii

Introduction

most common and to the study of local complications of renal transplantation. The key to successful therapy in these critically ill patients is the establishment of a prompt, accurate diagnosis of the underlying condition. Close interspecialty cooperation is needed to correlate the clinical, physical, radiologic, and pathologic findings. Our primary objective is to offer sound, detailed guidance in the evaluation of each of these complications. We cover the full range of techniques that have been successful in our hands and authoritatively documented in the literature. We describe the techniques and variations as performed with a variety of equipment, recognizing that some equipment is not always readily available and that some of our colleagues do not share our preference for, say, ultrasonography over computed tomography in some situations. In recent years, new percutaneous techniques have been developed for the nonsurgical management of some of the vascular and urologic complications of renal transplantation. Their main advantage is a definitively reduced morbidity and virtually no associated mortality. Among these techniques are transluminal angioplasty of stenotic arteriovenous fistulas for hemodialysis; transluminal angioplasty of transplant renal artery stenosis; percutaneous antegrade pyelogram, percutaneous nephrostomy drainage, and balloon dilatation of ureteral strictures; and therapeutic embolization of large arteriovenous fistulas after native nephrectomy. Chapter 11 offers a clear description of each of these techniques as it relates to specific problems. We hope that this volume will facilitate the diagnostic evaluation of local allograft complications and broaden the choice of diagnostic and therapeutic alternatives for patients. We hope also that it will encourage cooperation between the different specialties. W. R. Castañeda-Zuñiga

PARTI

Diagnosis of Systemic Complications


CHAPTER I

Chest Film in the Assessment of Myocardial and PencardJal Abnormalities Luis Cueto-Garda and W. R. Castaneda-Zuniga

Uremia causes several hemodynamic and metabolic abnormalities that increase the volume and pressure load of the heart.1 As a consequence, the myocardium becomes hypertrophic and eventually, dilated.2 In many cases, the pericardium is also affected.3 These cardiac changes influence the diagnostic and therapeutic attitudes of the physician who cares for the uremic patient because many patients die from the cardiac complications of their condition. Although echocardiography and nuclear medicine methods are gaining popularity, the electrocardiogram (ECG) and the routine chest film remain the basic tools for the cardiac evaluation of the patient with chronic renal failure (CRF). 3 It is important, then, to understand the advantages and limitations of the chest film in the diagnosis of the cardiac abnormalities of uremia, which are ventricular hypertrophy and dilatation, pulmonary congestion, acute pericarditis with or without effusion, tamponade, and pericardia! constriction. Of course, many of these changes may appear concurrently.

4

Cueto-Garcia and Castaneda-Zuniga

In this chapter, we review the sensitivity and specificity of the chest film in the diagnosis of these anatomic and hemodynamic alterations and compare its diagnostic value with that of physical examination, ECG, and echocardiography, which are the other most popular cardiological tools.

VENTRICULAR HYPERTROPHY Practically all patients with long-standing CRF have some degree of ventricular hypertrophy because of the abnormal work load of the heart as a result of hypervolemia, hypertension, and anemia.1 The initial stages may be missed on the chest film, and it has been our experience that with early use of hemodialysis and renal transplantation many young patients with CRF will not have an abnormal chest film. In patients with mild ventricular hypertrophy (wall thickness less than 20% greater than normal for the patient's age), the chest film does not show any alteration, whereas the ECG and echocardiogram are abnormal (fig. 1.1; table 1.1). When there is significant hypertrophy, the cardiac silhouette has a rounded apex known as a left ventricular contour (fig. 1.2A), with progression to clear-cut radiological cardiomegaly (fig. 1.2B). Figure 7 . 7 . Unremarkable chest film in patient with chronic renal failure and with ECG and ultrasonographic evidence of left ventricular hypertrophy.

Myocardial and Pericardial A bnormalities

5

Table 1.1. Usefulness of Routine Methods in Diagnosing Cardiac Complications in the Uremic Patient

Complication

Chest Film

Electrocardiogram

Echocardiography

Ventricular hypertrophy Mild Severe

+

++ ++

+++ +++

Ventricular dilatation Mild Severe

+ +++

Pulmonary congestion

+++

+++ +++ +++

Myocardial contractility Acute pericarditis (without effusion) Pericardial effusion

+

++

+

+++

Tamponade

+

++

Pericardial constriction

+

+

Note: A scale of (+) to (+++) is used, with (+) denoting the poorest demonstration.

Figure 7.2. Progressive enlargement of heart silhouette in patient with chronic renal failure. (A) Baseline radiograph; note left ventricular contour. (B) One

year later, heart is definitely enlarged despite adequate medical treatment and regular hemodialysis.

VENTRICULAR DILATATION Echocardiographic studies have shown that in CRF, the increase in the thickness of the ventricular walls is usually accompanied by some degree of ventricular dilatation. Again, as in ventricular hyper-

6


trophy, the initial stages are not apparent on the chest film (fig. 1.1). When there is significant dilatation, the heart is always enlarged; but the contribution of pericardia! effusion to this effect cannot be determined from the chest film alone (fig. 1.3).

Figure 1.3. (A) Admission chest film. (8) Decrease in heart size after treatment that led to regression of left ventricular dilatation and disappearance of pericardial effusion.

Myocardial and Pericardia/ A bnormalities

7

PULMONARY CONGESTION The chest film remains the best tool for the evaluation of pulmonary congestion, which can result from acute volume overload or irreversible ventricular dilatation. However, the chest film alone cannot differentiate between the two conditions because it does not show the extent of myocardial contractility (table 1.1 ).4

ACUTE PERICARDITIS AND PERICARDIAL EFFUSION Before the advent of hemodialysis, 50% of patients with end-stage renal disease suffered from pericarditis. 5 Now, about 15% of uremic patients have this complication, which sometimes starts when hemodialysis is instituted and is probably related to this treatment. Its appearance is a bad prognostic sign. Physical examination is probably more diagnostic than the chest film, ECG, or the echocardiogram, especially in the absence of a significant effusion. When more than 300 ml of fluid accumulates in the pericardial sac of a nondilated adult heart, the cardiac size increases on the chest film, the left border straightens, and the cardiophrenic angles become abnormal; these signs strongly suggest the presence of the effusion. In the uremic patient, however, because the heart is often already enlarged, the amount of fluid needed to produce radiological changes is greater; in many cases, it is difficult to make the diagnosis from the chest film (fig. 1.4). If cardiac enlargement appears suddenly in a patient in whom a recent chest film showed a normal heart size, and if there are no clinical or radiological signs of pulmonary congestion, a pericardial effusion is probably presFigure 1.4. Patient with large heart and signs of left ventricular failure. Pleural effusion, a common finding in patients with cardiac failure, is also present.

8


ent. In most cases, however, pericardial effusion is diagnosed most easily by echocardiography. 6

CARDIAC TAMPONADE In nonuremic patients, clinical signs of acute cardiac restriction in association with progressive cardiac enlargement strongly suggest tamponade. Again, however, the already enlarged heart of many uremic patients often makes the diagnosis difficult, even with hemodynamic evaluation. Nevertheless, if a chest tap is performed for tamponade in the uremic patient, the chest film usually shows a decrease in the heart size.

PERICARDIAL CONSTRICTION Pericardial constriction is a rare complication of uremia that is difficult to diagnose in the absence of gross pericardial calcification. In a nonuremic patient, the combination of a small cardiac silhouette and interstitial congestive changes suggests this complication, but in the uremic patient this picture may instead represent volume overload (fig. 1.5). Echocardiography is usually somewhat more helpful than the chest film. Figure 1.5. Patient with a small heart and signs of pulmonary congestion as a result of acute volume overload. Pericardial constriction was absent.

Myocardial and Pericardial A bnormalities

9

EFFECTS OF TREATMENT ON CHEST FILMS Among the therapeutic interventions that may influence the picture on the chest film, hemodialysis and renal transplantation are particularly interesting (fig. 1.6). It was through study of sequential radiographs that clinicians learned that heart size may fluctuate significantly. For example, in 1971 Mehbold and Gutman showed significant changes in heart size and the degree of pulmonary vascular congestion after peritoneal dialysis or hemodialysis.7 Such changes, which may appear within 24 hours of the procedure, result from acute volume depletion in a patient with volume overload, congestive heart failure, or both.

Figure 1.6. Changes in heart size with successful renal transplantation. (A) Before the operation, note increased left ventricular mass and pericardia! effusion. (B) Seven days after transplantation; sig-

nificant decrease in heart size with regression of ventricular mass and disappearance of the effusion. Simultaneous echocardiograms were obtained.

Starzl,8 Helin,9 and others have documented a significant regression in heart size after successful renal transplantation. For example, Helin found that about half of his patients with previously enlarged hearts had normal chest films 2 years after transplantation. Nevertheless, sequential radiographic examination is unable to answer two important questions: Is this decrease in heart size secondary to a decrease in the size of the heart chambers or to diminution in the amount of pericardia! effusion? And what is the status of myocardial contractility before and after hemodialysis or renal transplantation? The success of renal transplantation must be judged not only by its correction of metabolic abnormalities but also by its effectiveness in improving ventricular contractility.

70


CONCLUSION The chest film remains one of the most important routine methods for detecting and following the cardiac complications of uremia. Although it is unable to show mild ventricular hypertrophy or the status of myocardial contractility, it is a good tool, especially in conjunction with echocardiography, for the diagnosis of significant ventricular dilatation and pericardial effusion. Despite the introduction of new techniques, it remains the best way to evaluate the pulmonary changes consequent to volume overload or congestive heart failure in the patient with CRF.

REFERENCES 1. Capelli JP, Kasparian H: Cardiac work demands and left ventricular function in end stage renal disease. Ann Intern Med 86:261-267, 1977. 2. Lanfendorf R, Piranic CL: The heart in uremia: An electrocardiographic and pathologic study. Amer Heart J 33:282-307, 1 947. 3. Kjellstrand CM, Simmons RL, Buselmeier J, Najarian JS: Recipient selection. In: Transplantation. JS Najarian, RL Simmons (Eds.). Philadelphia: Lea & Febiger, 1972. 4. Hung J, Harris CJ, Uren RF,etal.: Uremic cardiomyopathy: Effect of hemodialysis on left ventricular function in end stage renal failure. N Engl J Med 302:547-551, 1980. 5. Comty CM, Wathen RL, Shapiro FL: Uremic pericarditis. In: Pericardial Diseases. DH Spodick, FA Davis (Eds.). Philadelphia: Lea & Febiger, 1976, p. 219. 6. Feigenbaum H: Echocardiography. Philadelphia: Lea & Febiger, 1976, p. 419. 7. Mehbold H, Gutman E: Changes seen on chest film following hemodialysis. Radiology 100:41-44, 1971. 8. Starzl F: Experience in Renal Transplantation. Philadelphia: WB Saunders, 1964, p. 383. 9. Helin B: Heart volume in human kidney transplantation. Acta Radio! Suppl 314, 1972.

CHAPTER 2

Echocardiography In Evaluating Effects on the Heart Luis Cueto-Garcia

Many pericardia!, myocardial, and valvular abnormalities have been identified in patients with chronic renal failure,1"7 and cardiovascular disease is the principal cause of death in these patients.8"12 Although the cardiac effects of chronic hemodialysis had been investigated extensively, however,13'14 surprisingly little was known about the effects of successful renal transplantation on the heart at the time we began our work at the National Institute of Nutritional Diseases in Mexico City. Because M-mode echocardiography permits sequential noninvasive evaluation of the anatomy and function of the heart,15"17 we used it in our studies of 30 normal volunteers and of 26 young (aged 17-39 years) uremic patients before and after successful renal transplantation from related living donors. In our initial study, which included 18 of these patients, we were struck by the extent and apparent rapidity of significant postoperative changes in the left ventricle. We thus studied an additional eight patients,

72

Cueto-Garcia

focusing on the immediate postoperative findings. Of the 26 patients, 22 had chronic renal failure as the result of glomerulonephritis, 2 as the result of interstitial nephritis, and 1 as the result of amyloidosis. In the remaining patient, the cause of renal failure could not be determined. Therefore, we caution that our findings may not be applicable to many older uremic patients, who often have arteriosclerosis, or to those with diabetes, which has its own effects on the cardiovascular system. We urge investigators at medical centers where such patients are candidates for renal transplantation to do similar studies of the cardiac effects of this operation.

METHODS Our 12 male and 14 female patients were studied by M-mode echocardiography 1 week before transplantation and 1-67 weeks afterward. In seven cases, two postoperative echocardiograms were made, the first 1 week after the transplant and the other 3-5 weeks later. Before the operation, all patients were undergoing regular hemodialysis via Cimino-Brescia arteriovenous shunts, which were still open at the time of the postoperative studies. Twenty-one patients had systemic hypertension preoperatively that required drug treatment (diuretics, beta blockers, vasodilators), and all patients were anemic. Postoperatively, only one patient still required antihypertensive drugs; and the blood pressure, hemoglobin level, and creatinine clearance were normal or nearly so in all patients. All were receiving corticosteroids and immunosuppressive drugs postoperatively. All echocardiograms were obtained with the patient in the left lateral decubitus position, with care taken to position the patient and transducer identically for each study.18"20 An Echo IV Electronics For Medicine echocardiography unit with a 2.25-mHz transducer was used, and measurements were made according to accepted standards.21"24 Because we found that there were no significant changes in the heart rates of the patients after renal transplant, the absolute values for preoperative and postoperative chamber size and cardiac function could be compared.25

Heart Echocardiography

13

FINDINGS Left ventricular hypertrophy and dilatation are common in uremic patients, a fact that has been documented by methods as simple as the routine chest film and as sophisticated as hemodynamic studies and echocardiography.1"3'7'26 For example, in our patients, the left ventricular internal diastolic dimension [LVID(d)] averaged 5.04 ± 0.62 cm preoperatively (normal 4.3 ± 0.6 cm), while the left ventricular wall thickness (LVWT) averaged 1.16 ±0.16 cm (normal 0.77 ± 0.11 cm) and the left ventricular mass (LVM), 286 ± 64.4 g (normal 127 ± 30 g). In all cases, the end-diastolic volume was increased preoperatively, and thus the stroke volume and cardiac output (CO) were above normal. Thus, the CO was 6.47 ± 2.83 liters/min. in the uremic patients preoperatively, in comparison with 3.93 ± 1.93 liters/min. in the normal volunteers. The effects of uremia on the right ventricle were less striking: the rightventricular internal diastolic dimension [RVID(d)] was 1.6 ± 0.50 cm in the patients preoperatively and 1.06 ± 0.45 cm in the volu nteers. We did not study the effects of hemodialysis on the heart, but other investigators have found only modest changes. For example, Vaziri and Prakash recorded a mean predialysis LVID(d) of 5.0 ± 0.64 cm (which is very close to the value we found) and a mean postdialysis value of 4.7 ± 0.5 cm.14 The first studies of posttransplant changes in the hearts of uremic patients, made by standard radiography techniques, indicated a regression in heart size but could not distinguish the contribution of the pericardial effusion so common in these patients from that of ventricular dilatation.27'28 Other workers have used M-mode echocardiography, but the design of these studies revealed nothing of the time course of the changes.29"31 We found that significant changes in the left ventricle could be detected in some patients as early as 1 week after successful renal transplantation. Thus, in the four patients who had elevated LVMs preoperatively and had two echocardiograms postoperatively, the first 1 week after the operation and the second on the sixth week postoperatively, the LVMs had decreased an additional 13-65% (figs. 2.1 and 2.2). Further evidence of the rapidity with which the heart responds to the correction of the metabolic and hemodynamic abnormalities of uremia can be seen by comparing the LVID(d), LVWT, and LVM of patients studied within 6 weeks of operation with those of the patients studied later (table 2.1).

14

Cueto-Garcia

Figure 2.1. Change in left ventricular mass (measured in grams) soon after renal transplantation; solid lines represent patients who had one postoperative echocardiogram, the dotted lines those who had two within the first 6 weeks. BSRT and ASRT = before and after successful renal transplantation. Figure 2.2. In our initial study of 18 patients, the preoperative left ventricular mass (LVM) was above normal (dotted line) in all. At 3 to 67 weeks postoperatively, the LVM had declined in all, and in 10 patients it was within the normal range.


75

Table 2.1. Effects of Renal Transplantation on the Left Ventricle Patient Group3

LVID(d) (cm)

LVWT (cm)

LVM

Controls

4.3 ± 0.6

0.77 ± 0.11

127 ± 30

Early group Preoperative Postoperative

5.1 ± 0.57 4.6 ± 0.9

1.1 ±0.24 0.93 ± 0.22

287 ± 118 182 ± 78

Late group Preoperative Postoperative

5.0 ± 0.6 4.5 ± 0.55

1.14 ± 0.17 0.9 ± 0.09

279 ± 56 173 ± 44

(g)

a Early group = 1 2 patients studied within 6 weeks of transplantation; late group = 14 patients studied 12-67 weeks posttransplant; note the similarity of the postoperative values in the two groups.

Several functional changes were also noted postoperatively. For example, the end diastolic volume decreased significantly (from 134 ± 52 ml to 96.4 ± 43 ml; p < 0.0025), although the end systolic volume did not. Therefore, the stroke volume decreased (fig. 2.3). Also, the cardiac output declined to normal, and the stroke work decreased significantly (from 150.6 ± 70.6 g/m per beat to 74.6 ± 44.2 g/m per beat;p < 0.0005). Our findings indicate that in patients with uremia, the principal cause of the abnormally high cardiac output is an increased stroke volume —not an increased heart rate, as maintained by others. From our results, it also appears that the arteriovenous shunt used for hemodialysis is not a significant contributor to the hemodynamic changes in uremia; in our patients, the end diastolic volume and cardiac output decreased postoperatively even though the shunt was still open. Again, these findings contradict those of other investigators.7'32 Another conclusion that can be drawn from our findings is that the pattern of LVM regression after transplant is different from that seen in other circumstances. For example, replacement of the aortic valve to correct aortic regurgitation causes an early decline in the left ventricular volume. 33 - 34 In such patients, the LVWT tends to increase postoperatively, whereas in our patients it either declined or was unchanged. In our patients, the transplant led to a significant fall in both the blood pressure and the diastolic volume. Both of these affect the LVM,7'17'33"39 and it is not possible to determine the relative contributions of the two factors to the increased LVM preoper-

16

Cueto-Garcia

atively or to the postoperative regression. Decreases in LVM as a result of the relief of pressure overload have certainly been well documented.38"42 Changes that have been noted in LVM after medical treatment of essential hypertension are believed to result from changes in the LVWT.43 On the basis of these findings, the mechanism of LVM regression seen in our patients —that is, significant decreases in LVWT and end diastolic volume —is apparently unique. Figure 2.3. Changes in the end diastolic volume (upper value) with little change in end systolic volume (ESV) lead to a significant decrease in the stroke volume (SV).

CONCLUSIONS Our studies of patients with chronic renal failure by M-mode echocardiography before and after successful renal transplant show that the correction of metabolic and hemodynamic abnormalities by the allograft brings about a regression of left ventricular mass


77

that appears to begin immediately after the operation. This regression, which seems to result from decreases in the left ventricular wall thickness and end diastolic volume, brings the parameter within normal limits in many patients. We cannot yet say what percentage of patients will eventually have a normal left ventricular mass because we have not performed echocardiograms after the 67th week. Nonetheless, we believe it is encouraging that, at least in these young, nondiabetic patients, recovery of normal or nearnormal cardiac morphology and function appears to be so common after successful renal transplantation.

REFERENCES 1. Langendorf R, Pirani CL: The heart in uremia: An electrocardiographic and pathologic study. Amer Heart J 37:282-307, 1 974. 2. Cruz IA, Bhatt GR, Cohen HC, Click G: Echocardiographic detection of cardiac involvement in patients with chronic renal failure. Arch Intern Med 1 38:720-724,1978. 3. Kleiger R, de Mello VR, Malone D, et al.: Left ventricular function in end-stage renal disease. South Med J 74:819-825, 1981. 4. Yoshida K, Shina A, Asano Y, Hosoda S: Uremic pericardia! effusion: Detection and evaluation of uremic pericardia! effusion by echocardiography. Clin Nephrol 13:260268,1980. 5. Luft FC, Gilman J K, Weyman AE: Pericarditis in the patient with uremia: Clinical and echocardiographic evaluation. Nephron 15:17-28, 1975. 6. Kersting F, Brass H, Heints R: Uremic cardiomyopathy: Studies on cardiac function in the guinea pig. Clin Nephrol 10:109-11 3, 1978. 7. Capelli JP, Kasparian H: Cardiac work demands and left ventricular function in endstage renal disease. Ann Intern Med 86:261-267, 1977. 8. Parsons FM, Brunner FP, Gurland HS: Combined report on regular dialysis and transplantation in Europe. Proc Eur Dial Transplant Assoc 8:3, 1 971. 9. Gurland HJ: Combined report on regular dialysis and transplantation in Europe. Proc Eur Dial Transplant Assoc 1 0:1 7-21,1 973. 10. Casaretto AA, Marchiaro TL, Bagdada JD: Hyperlipidemia following renal transplant. Trans Am Soc Artif Intern Organs 19:154-157, 1973. 11. Merrill JP: Cardiovascular problems in patients on long-term hemodialysis. JAMA 228:1149-1153,1974. 12. Nichols AJ, Catto GRD, Edward N, Engeset J, McLeod M: Accelerated atherosclerosis in long-term dialysis and renal transplant patients: Fact or fiction? Lancet 1:276278,1980. 13. Cohen MV, Diaz P, Scheurer J: Echocardiographic assessment of left ventricular function in patients with chronic uremia. Clin Nephrol 12:156-1 62,1979. 14. Vaziri ND, Prakash R: Echocardiographic evaluation of the effect of hemodialysis on cardiac size and function in patients with end-stage renal disease. Am J Med Sci 278:201-206, 1979. 15. Cueto L, Arriaga J: Ecocardiografia en medicina interna modo M: El estado del miocardio. (la de 3 partes). Rev Inv Clin (Mex) 31:169-1 76,1979.

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16. Ehsani AA, Hagberg JM, Hudson RC: Rapid changes in left ventricular dimension and mass in response to physical conditioning and disconditioning. Am J Cardiol 42:52-56, 1978. 17. Cueto L, Aragon M, Troyo P: La secuenicia clinica ecocardiografica y hemodinamica en la fisula arteriovenosa cerebral. Arch Inst Cardiol Mex 49:634-647,1979. 18. Clark RD, Dorcuska K, Cohen K: Serial echocardiographic evaluation of left ventricular function in valvular disease including reproducibility guidelines for serial studies. Circulation 62:564-565,1980. 19. Wong A, Shah PM, Taylor RD: Reproducibility of left ventricular internal dimensions with M-mode echocardiography: Effects of heart size, body position and transducer angulation. Am J Cardiol 47:1068-1074, 1981. 20. Ditchey RV, Schuler G, Peterson K: Reliability of echocardiographic and electrocardiographic parameters in assessing serial changes in left ventricular mass. Am J Med: 70:1042-1049, 1981. 21. Sahn DS, de Maria A, Kisslo J, Weyman A: The Committee on M-mode Standardization of the American Society of Echocardiography: Recommendations regarding quantitation in M-mode echocardiography: Results of a survey of echocardiographic measurements. Circulation 58:1072-1083, 1978. 22. Bennett DH, Evans DW: Correlations of the left ventricular mass determined by echocardiographic measurements. Br Heart J 36:981-984, 1974. 23. Feigenbaum DH, Popp LR, Wolfe SB, et al.: Ultrasonic measurements of the left ventricle. Arch Intern Med 129:461-466, 1972. 24. Gaasch WH: Left ventricular thickness to wall thickness ratio. Am J Cardiol 43:11891194,1979. 25. de Maria AN, Newman A, Schubart PS, Lee G, Mason DT: Systemic correlation of cardiac size and chamber performance determined with echocardiography and alterations of the heart rate in normal persons. Am J Cardiol 43:1 -9, 1 979. 26. Dean J: Relation of cardiac enlargement to hypertension in acute and chronic glomerulonephritis. Am J Med 1:161-167, 1946. 27. Starzl T: Experience in Renal Transplantation. Philadelphia: WB Saunders, 1964, p. 383. 28. Helin B: Heart volume in kidney transplantation. Acta Radiol Suppl 314, 1972. 29. Zabagoitia M, Aillaud M, Ceto L, et al.: Ecocardiografia antes y despues del transplante renal. Presented at the 1 2th National Mexican Congress of Cardiology, Morelia, Michoacan, December 1981. Libro de resumenes, p. 1 91. 30. Ikaaheimo M, Linnatuoto M, Huttunen K, et al.: Effects of renal transplantation on left ventricular size and function. Br Heart J 47:155-160, 1982. 31. Riley SM Jr, Blackstone EH, Sterling WA, et al.: Echocardiographic assessment of cardiac performance in patients with arteriovenous fistulas. Surg Gynecol Obstet 146:203-208,1978. 32. Bibra H, Castro L, Autenrieth G, McLeod A, Gurland HJ: The effects of arteriovenous shunts on cardiac function in renal dialysis patients: An echocardiographic study. Clin Nephrol 5:205-209, 1978. 33. Schuler G, Peterson KL, Johnson A, et al.: Serial non-invasive assessment of left ventricular hypertrophy and function after surgical correction of aortic regurgitation. Am J Cardiol 44:585-594, 1979. 34. Gaasch WH, Andrias CW, Levine HS: Chronic aortic regurgitation: The effect of aortic valve replacement on left ventricular mass and function. Circulation 58:825836,1978. 35. Neff MS, Kim KE, Persoff M, Oneseti G, Swartz C: Hemodynamics of uremic anemia. Circulation 43:876-883, 1971. 36. Del Greco F, Simon NM, Roguska J, Walker C: Hemodynamic studies in chronic uremia. Circulation 40:87-95, 1969.


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37. Papadimitriou JM, Hopkins BE, Taylor RD: Regression of left ventricular dilatation and hypertrophy after removal of volume overload. Circ Res 35:127-1 35, 1974. 38. Sasayama S, Ross J Jr, Franklin D, et al.: Adaptations of the left ventricle to chronic pressure overload. Circ Res 35:1 72-1 78, 1976. 39. Schlant RC, Felver JE, Heymesfield SB, et al.: Echocardiographic studies of left ventricular anatomy and function in essential hypertension. Cardiovasc Med 2:477491,1977. 40. Henry WL, Borow RO, Borer JS, et al.: Evaluation of aortic valve replacement in patients with valvular aortic stenosis. Circulation 61:814-825, 1980. 41. Hall O, Hall E, Ogden E: Cardiac hypertrophy in experimental hypertension and its regression following re-establishment of normal blood pressure. Am J Physiol 174: 175-178, 1953. 42. Froslich ED, Tarazi RC: Is arterial pressure the sole factor responsible for hypertensive cardiac hypertrophy? Am J Cardiol 44:959-963, 1 979. 43. Wollam GL, Hall D, Douglas MB: The time course of regression of left ventricular hypertrophy in treated hypertensive patients. Proc 31st Ann Sci Session, Amer Coll Cardiol 951, 1982.

CHAPTER 3

Radiology of Pulmonary Complications David W. Hunter and Jeffrey Crass

There is no question about the importance of pulmonary complications in the transplant patient. Although a few changes are quite benign (for example, mediastinal lipomatosis), most of the abnormalities either reflectaseriousnonpulmonary problem (likecardiacrenal failure or thrombo-embolic disease) orsignal the development of pulmonary infection. An outline of pulmonary complications seen in transplant patients is presented in table 3.1. Infection remains the leading cause of death among transplant patients, and pulmonary infections are the most common of the fatal infections.1"4 The incidence of pulmonary complications after transplantation ranges from 9 to 25%, with a mortality rate among this group of from 24 to 50%. The mortality rate for those with infectious pulmonary complications is slightly higher, ranging from 24 to 56%. Mortality is higher in males.4 Of patients with a primary pulmonary process, 40-44% will develop a secondary pulmonary infection. The mortality for these patients is staggeringly

Pulmonary Complications

27

high at 90% or greater. 5 - 6 From 27 to 50% of transplant patient deaths are a result of a pulmonary complication. 3 Recent work with lower dose immunosuppression has dropped the mortality rate from pulmonary complications, especially infection, below 20%.7 The morbidity and mortality of both infectious and noninfectious pulmonary problems are clearly reduced by rapid diagnosis and early institution of proper therapy.5'8 Previous articles have not adequately stressed the role of the radiologist in the care of these patients. Table 3.1. Pulmonary Complications Following Renal Transplant Infectious Bacterial Gram-positive —Community acquired Staphylococcus Streptococcus Pneumococcus Gram-negative —Hospital acquired Klebsiella Pseudomonas Escherichia coli Fungal Asperigillus No car dia Cryptococcus Candida Viral Cytomegalovirus Protozoan Pneumocystis car/nil Noninfectious Pulmonary edema Pulmonary embolus Bland embolus Septic embolus Pulmonary hemorrhage Malignancy Soft tissue calcification Aspiration pneumonia Mediastinal lipomatosis latrogenic complications Following biopsy Pneumothorax/Hemothorax Bronchopleural fistula

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THE CHEST X-RAY The chest X-ray fulfills three important functions in the case of the transplant patient with a pulmonary complication. First, analysis of the pattern of disease may limit the number of diagnostic possibilities so that rational temporary therapy can be started while definitive tests are completed. Early analyzable abnormalities should be present in most cases because the chest X-ray is abnormal (or becomes so within 48 hours) in 84-100% of patients with clinical and physical examination evidence of pulmonary disease.5'8'9 Second, the disease can be accurately localized before bronchoscopy, needle biopsy, or open-lung biopsy. Third, the chest X-ray is critical for the detection of silent pneumonia.4 The diagnosis of pneumonia is usually established radiologically.10 In one large series of transplant patients with fever,10 39% of the patients with pneumonia had the diagnosis made by chest X-ray when there were no findings on physical examination. In another series,7 15% of patients with a pulmonary complication had a positive chest X-ray without respiratory symptoms. The most common symptoms of patients with pneumonia are fever and malaise, with only about 25-33% of patients having cough or dyspnea as a presenting symptom.10"12 Although the chest X-ray may be nonspecific in some of these immunocompromised patients and therefore of little diagnostic value,13 we believe, as do others,5'14 that it is quite helpful especially when evaluated in conjunction with clinical data and preceding X-rays. This interpretive method, which parallels that recommended in the standard pulmonary radiologic textbooks, allows one at least to offer a restricted differential diagnosis that is ordered on the basis of probability of occurrence.

Assessment and Differential Diagnosis: A Stepwise Approach From the radiologist's perspective, the primary task in evaluating the chest X-ray of a transplant patient is to describe clearly any abnormalities and then, if possible, to compare with previous X-rays to determine the rate and direction of change. If the X-ray is normal, nothing further need be done except to recommend appropriate follow-up.


23

If the X-ray is abnormal, the amount of time since transplantation must be known to refine the differential diagnosis.s>7>10,14 During the first 1-2 weeks after transplantation, most pulmonary complications are postoperative, including pulmonary embolus, aspiration pneumonia, and pulmonary edema. The infections that do occur are almost all bacterial, usually gram-negative.6'10 The intermediate time period, from 2 weeks to 4 months, is the time of greatest susceptibility to infection while the transplant is the least stable and immunosuppressive drug levels are maximal. 7 Common infecting agents at this time include cytomegalovirus, opportunists like Nocardia and Pneumocystis, and the true fungi. During the late period—after 4 months—if a transplant recipient is outside of the hospital, and doing well with stable transplant renal function, most pulmonary infections are caused by the usual community pathogens, including pneumococcus, streptococcus, staphylococcus, and hemophilus influenza.6 If, however, the transplant function is poor and/or the patient is in the hospital being treated for rejection, infection is most likely caused by an opportunist—especially the fungi and opportunistic gram-negative bacteria.6 Additional clinical data may seem to favor one particular diagnosis. However, speculation about the precise pathologic diagnosis must be done cautiously because the radiologic presentation of illness is less specific in the immunocompromised patient. Using a stepwise approach, we can develop a flow chart that indicates which diagnoses are more likely for any given radiologic presentation (table 3.2).

INFECTIOUS COMPLICATIONS About 70-80% of transplant recipients acquire an infection, and 15-25% of these are pulmonary. 15 Infection is the leading cause of death among transplant patients, with pulmonary infection the most common.1 New immunosuppressive regimens are changing this picture, however, and for patients with diabetes mellitus, the leading cause of death is now sudden death (usually cardiac in origin).16 In three studies of pulmonary complications following transplantation, infection was present in 61-65% of the cases.3'7-8 Two studies distinguished between primary and secondary infections. Bacterial infections accounted for 33 and 40% of the primary

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infections and were more common than fungal or viral infections.3'5 In four other series that grouped primary and secondary infections, bacteria were even more prominent, accounting for 64-75% of all infectious complications.8'10'11'14 Table 3.2. Stepwise Approach to the Diagnosis of Pulmonary Complications Alveolar * Diffuse Time after Transplant

Relative Frequency Common

Early (0-2 wk)

Intermediate (2 wk4 mo) and Late (4 mo2yr)

Very Late (>2 yr)

Less Common

Common

Less Common

Lobar or Focal Gm (— ) bacteria P. embolus Aspiration Anaerobic bacteria Bacteria (any) Aspergillus No car dia

P. embolus TB Candida

Multifocal or Patchy P. embolus

Central or Perihilar P. edema

Widespread to Periphery Aspiration

P. edema (severe) Mixed bacteria StaphyloP. edema PneumoPneumocystis cystis coccus carinii can' nil P. embolus (late) Aspergillus Mixed No car dia bacteria Cytomegalo- Fungus Candida (overwhelmCryptococcus virus P. edema ing) (bibasilar) Strongyloides Septic P. hemorrhage embolus P. edema (bibasilar)

Common Less Common

CAVITATING LESIONS

Common

Less Common

Staphylococcus Gm (— ) bacteria Anaerobic bac. Aspergillus No card fa TB

Staphylococcus Aspergillus No car dia Septic embolus Candida

Aspergillus


25

A more recent study using lower doses of steroids and azathioprine7 confirmed other reports that the lower doses of immunosuppressives reduced the number of opportunistic infections, particularly fungal and viral. In this study, bacteria accounted for 75% of the primary pulmonary infections.

Interstitial Nodular/Masslike Streaky or Linear P. edema (mild)

Small (1-3 mm) or Miliary

Multiple Moderate or Large

Pneumocystis carinii (early) Cytomegalovirus

Cytomegalovirus

Aspergillus No card ia

Virus (other than cytomegalovirus)

TB Cryptococcus Histoplasma Coccidioides

Staphylococcus Pseudomonas Septic embolus

Lung rrtetastases Lymphoma

Aspergillus No card la

Single Small or Large

Aspergillus No card ia Histoplasma

Lipomatosis Lymphoma Lung carcinoma

Aspergillus No card!a

Histoplasma

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Hunter and Crass

Certain clinical factors have been associated with an increased risk of infection. These include leukopenia, a recent increase in steroid dose for treatment of rejection, and decreased renal function.2-5'7'12 Less definite but suggestive risk factors include associated diabetes mellitus, older age, male sex, postoperative complications, liver failure, prior antibiotic therapy, cadaver transplant, and poor antigen match.2'10'11'16 Clinical factors associated with a poor prognosis for infection include elevated creatinine, leukopenia, concurrent cytomegalovirus infection, diabetes mellitus, and a larger total dose of steroid and/or a larger number of treatments for rejection. 5 ' 10 Bacteria Tuberculosis Although tuberculosis—especially the reactivation type —has been a feared potential complication of immunosuppressive therapy, the actual incidence is quite low. Onset is usually insidious, but the severity of the disease is generally greater;17 mortality is directly related to the time between the onset of symptoms and the start of treatment. Five of nineteen patients in one study18 had a positive chest X-ray before the development of symptoms, and most patients develop a positive chest X-ray.18"20 The most common finding is an upper lobe alveolar infiltrate that may cavitate (fig. 3.1).4'17'19 Almost as common is a miliary nodular pattern that is associated with widespread, hematogenous dissemination from the reactivated focus.18 Atypical mycobacteria are seen, but the usual organism is Mycobacterium tuberculosis homin/s, which is susceptible to the standard drugs. Other Bacteria Bacterial infection acquired outside the hospital has an X-ray picture and acute clinical presentation similar to those seen in normal nontransplanted patients. The most common organisms are streptococcus, staphylococcus, and pneumococcus. 5 Nosocomial infections are more often due to gram-negative organisms, especially K/ebsie/la, Escherichia cofi, Pseudomonas, and Aerobacter. The most common radiologic presentation, occurring in more than two-thirds of all bacterial infections, is a focal, lobar, alveolar infiltrate that can rapidly cavitate (figs. 3.2 and 3.3).7'17'21'22 Very rapid cavitation usually signals the presence of anaerobic bacteria.17 Less


27

common gram-negative organisms, especially Legionella and Pittsburgh pneumonia agent, have recently been reported to be more common than has been expected, 12 and both infections have the same radiographic appearance as other gram-negative infections.

Figure 3.1. Left upper lobe alveolar infiltrate, 1974, on PA (A) and lateral (B) films. Battey bacillus isolated from sputum. (C) Four years later, 1978. The patient developed a recurrence with nodular infiltrates in the left and right upper lobes.

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Figure 3.2. (A) Klebsiella pneumonia presenting as a left lower lobe alveolar

infiltrate. (B) Cavitation occurred within 2 weeks.

Figure 3.3. (A) Pseudomonas pneumonia presenting as a right lower lobe, basilar infiltrate. The density in the right midlung is a fluid collection associated with

mild fluid overload. (B) Within 72 hours, the fluid "pseudomass" has cleared and the pseudomonas infection is clearly cavitating.

A less common radiologic presentation for a bacterial infection is one of ill-defined, diffuse, patchy infiltrates resulting from endobronchial or (more commonly) hematogenous spread.14 This bronchopneumonia pattern is quite common with staphylococcus infections (fig. 3.4) and is also seen in pseudomonas infections.21'23 When a pleural effusion is seen in conjunction with infection, especially if the effusion is unilateral and quite large, empyema must be strongly suspected.7'14 Secondary or superinfectionsare usually caused by gram-negative organisms. The X-ray indicates worsening of the primary process in spite of apparently adequate therapy.


29

Figure 3.4. Multiple bilateral, small to moderate-sized nodular infiltrates with hazy margins. Staphylococcus isolated from trachea! aspirate.

Fungi The incidence of fungal infections has fallen recently with the advent of lower dose immunosuppressive therapy.3'7'10 Fungal infection most commonly occurs following, or in conjunction with, bacterial or viral infection1'4-11 in the late (more than 4 months) posttransplant period. Nocardia Nocardia causes a common primary infection in the period of 1 to 4 months after transplantation.5 The lung is the primary site of infection in most cases, and an epidemiological study of one hospital outbreak 24 revealed a single contaminating source in the air supply. The clinical presentation is one of a several-day illness with fever, sweats, productive cough, and occasional dyspnea. Arterial oxygenation is usually not severely depressed, even in cases with extensive radiologic disease.5 Five of eight patients in one series had pleuritic pain.5 Only one-third of cases remained confined to the lung, with the commonest site of spread being the brain.22'25 Nocardia is almost never seen as a secondary invader. The radiologic presentation is either a localized alveolar infiltrate (fig. 3.5) 13>22 ' 25 or, less commonly, multifocal, moderate-sized nodules with indistinct margins (fig. 3.6). 5 - 7 ' 17 ' 23 The nodule or infiltrate may cross fissures and may involve the pleura. From 50 to 90% of patients will develop cavities within 1-2 weeks of presentation.5'7'17'21'25 Empyema can occur; hilar involvement is rare. Treatment with sulfonamides is frequently successful but needs to be continued for at least 1 year to prevent a relapse.13

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Figure 3.5. Nocardia pneumonia presenting as a right upper lobe alveolar infiltrate.

Figure 3.6. Nocardia pneumonia presenting as multiple bilateral nodular infiltrates with early cavitation, especially on the left.

Aspergillus Aspergillus causes either a primary or secondary infection during the intermediate (2 weeks to 4 months)5'10 or late (more than 4 months)1'10 time period. Primary infections usually occur in patients undergoing treatment for rejection.1'5 Two studies indicated that secondary infection following primary bacterial infection and antibiotic therapy was the more common presentation.3'10 The lung is the primary site of infection in almost all patients, but dissemination occurs in 20-50%.13 The usual clinical presentation is fever and malaise progressing over several days to a nonproductive cough. Pleuritic pain occasionally occurs, 26 perhaps largely due to the organism's tendency to occlude vessels.13 This pain may lead to an erroneous diagnosis of bland pulmonary embolus. Arterial oxygenation is usually preserved in these infections, however, even with significant radiologic disease.5 Aspergillus is a commensal that can be found in the sputum of many hospitalized patients. Diagnosis therefore depends upon biopsy rather than sputum cultures. The radiologic presentation seems fairly well divided between multifocal, "shaggy-edged" nodules5'7'14-17'25 and a localized, fairly well-defined alveolar infiltrate (fig. 3.7).2'8>10'21~23 Both types have a predilection for the upper lobes,3 and both nodules and infiltrates commonly cavitate. Radiologic and clinical progression is slower than with bacterial or Pneumocystis infections.14 Therapy with amphotericin B can be successful but needs to be prolonged, possibly for as long as 1 year.13


31

Figure 3.7. Aspergillus pneumonia presenting as a left lower lobe, large masslike infiltrate.

Other Fungi

Candida remains the most commonly isolated fungus;1 but since it colonizes the upper airway in almost all transplant patients, its role as a significant pathogen must be questioned in most cases. Even if it can be cultured from the blood, its significance is suspect especially if the patient has an indwelling venous catheter.9 Primary candidal pneumonia is rare,17 but well-documented cases of secondary candidal pneumonia exist. 1 Histoplasma and Coccidioides infections are rare in the transplant population, even in endemic areas.13-27 They may have minimal or no symptoms. 13 Like tuberculosis, they seem to be a reactivation process,27 and X-ray findings may be absent until shortly before death. Cryptococcus in the lung may produce minimal or no symptoms because it elaborates no toxin.5'13 It may, however, disseminate to the brain and meningesand be rapidly fatal.13 It isa primary invader that only rarely superinfects. 5 Phycomycetes are seen very rarely in transplant patients. They are more common in patients with malignancy, especially leukemia. They are known for vascular invasion leading to a clinical picture of pulmonary infarction.13 The radiologic appearance of all fungal infections is similar to that of Aspergi/lus, being either a localized alveolar process or, more commonly, 21 multifocal, moderate-sized nodules or patchy infiltrates with cavitation.4'5'26 One or more patchy alveolar infiltrates are probably the original presentation in most cases, with "nodularity" and multifocal distribution developing later.21-22

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The most common radiologic presentation of the various types of fungi is shown in the accompanying tabulation. Fungus Candida Coccidioides Cryptococcus Histoplasma

Presentation Multifocal, patchy infiltrates with occasional cavitation.12 Multifocal, small, "almost miliary" nodules without cavitation. 23 Multifocal, patchy infiltrates with cavitation,7'13 or small, "almost miliary" nodules. 7 Interstitial nodular, diffuse infiltrate with small nodules (fig. 3.8),27 or a cavitary nodular

mass. 21 Figure 3.8. Histoplasmosis presenting as an interstitial nodular infiltrate.

Viruses Cytom egalo virus Cytomegalovirus is the most common single infecting organism in transplant patients. 5 - 28 From 60 to 96% of transplant patients have been reported to have evidence of past or present cytomegalovirus.6'28'29 Cytomegalovirus further compromises the already impaired transplant patient's immune mechanism,29 which results in a 50% or greater rate of secondary invasion.5'27 Cytomegalovirus is usually present with another organism, especially Pneumocystis, 13,14,29 and it is present in 47% of all pulmonary infection deaths.26 The clinical picture is often confusing, with several days to a week of cyclic fever and other nonspecific symptoms but with-


33

out respiratory symptoms.3'3 Cytomegalovirus infection most commonly occurs during the intermediate (1-4 months) posttransplant period, with a peak incidence at 3 months. It is very rare after 1 year. 5 - 28 The typical radiologic appearance of cytomegalovirus is an interstitial nodular infiltrate (fig. 3.9). The streaky, interstitial component may predominate, 3 - 29 but the distinctive pattern is that of diffuse, peripheral nodules measuring 1-3 mm.4'5'7'14'17'26 A normal chest X-ray does not exclude cytomegalovirus; symptoms and lab abnormalities precede X-ray changes by several days to a week. 28 In one series, the chest X-ray was positive in only 2 of 7 cases of cytomegalovirus;11 and in two other series, the nodular pattern was present in only 7 of 21 cases21 and 8 of 48 cases.17 Cavitation is not seen.21 The differential diagnosis of this miliary nodular pattern includes fungal disease, in which case the nodules are usually larger; tuberculosis; septic emboli, including hematogenous dissemination of staphylococcus; and other viral infections, including measles and varicella. The nodular pattern is obscured in mixed infections.7 Wandering atelectasis has also been noted in patients with cytomegalovirus. Pulmonary viral infections other than cytomegalovirus are quite rare in transplant patients.

Figure 3.9. Cytomegalovirus in its typical presentation. The patient was symptomatic but had a normal chest X-ray (A) when frst examined. Seventeen days later (6), the bilateral central interstitial pattern is well developed. Three days later (C), it has progressed to a bilateral alveolar infiltrate with areas of "acinarization."

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Hunter and Cross

Protozoa Pneumocystis carinii Pneumocystis carinii is a relatively common opportunistic infection occurring in the intermediate (2 weeks to 4 months) and late (more than 4 months) posttransplant periods. It is very commonly associated with cytomegalovirus infection,5'26 The clinical symptoms may be rapidly progressive from the start; but more commonly, the onset is slow with moderate dyspnea out of proportion to other symptoms, especially dry cough and fever. Auscultatory findings may be minimal, even with prominent X-ray changes.14 Once established, however, the infection becomes rapidly worse. Hypoxia, dyspnea, and cyanosis become severe, and the mortality is high.8'10-11 The organism cannot be cultured, so timely diagnosis depends on the recognition of early radiologic changes and prompt open-lung biopsy. The incidence of pneumocystis infection after transplant is decreased in patients receiving low-dose immunosuppression. It has also been decreased by prophylactic use of suifonamides. Very early in the disease, the radiologic picture is one of a fine reticular, perihilar interstitial infiltrate.11'23'26 As it spreads from the hila, it becomes more "acinar"25 and then very rapidly evolves into a diffuse, patchy, alveolar process that spreads and consolidates quickly over 1-3 days (fig. 3.10). The periphery of the lung is frequently less involved until late in the course.14'17'25 Pleural effusion and hilar adenopathy are rare,22-26 and the infiltrate does not cavitate.2'21 At each stage in the disease, the primary radiologic

Figure 3.10. Pneumocystis carinii pneumonia showing minimal bilateral (best seen at right base) interstitial infiltrates

early (A) but in 11 days progressing rapidly (B) to a diffuse interstitial pneumonia.


35

differential diagnostic concern is pulmonary edema, which may be associated with rejection. The two main differentiating factors are that Pneumocystis carinii has less or no evidence of cardiac dysfunction; and that clinical symptoms, especially when Pneumocystis is associated with cytomegalovirus, precede rather than follow any decrease in renal function.3'28 Overwhelming infection by fungi or mixed bacteria could have a similar X-ray appearance as latestage infection by Pneumocystis. Radiographic clearing in pneumocystis infection occurs over a 2-week period, lagging behind clinical improvement. Miscellaneous Infections A few transplant patients have reportedly been infected by the helminth Strongyloides stercora/is.30~32 The disease, which is seen in the southern United States and in tropical countries, is often disseminated. Pulmonary findings are usually mild but can be severe. The more common radiologic appearance is a diffuse alveolar infiltrate that is indistinguishable from other diffuse fungal or bacterial infection. Aspiration Pneumonia Aspiration pneumonia occurs most commonly in the immediate postoperative period following any surgery the patient may have, including the original transplant.4 It also occurs in patients who develop problems swallowing or coughing secondary to central nervous system infection. 8 The radiologic appearance is similar to that seen in the nontransplant population with diffuse, bilateral but asymmetric alveolar infiltrates4-8 that develop rapidly over 2448 hours and then clear slowly over 5 days to 2 weeks unless complicated by secondary infection (fig. 3.11). Figure 3.77. Aspiration pneumonia in the postoperative period presenting as a dense left lower lobe infiltrate that obscures the diaphragm.

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Hunter and Crass

NONINFECTIOUS COMPLICATIONS Pulmonary Edema Pulmonary edema is the most common noninfectiouspost transplant complication, representing 26-29% of all pulmonary complications in two series3'7 and 11 % of patients with pulmonary infiltrates and fever in another series. 5 It results from cardiac disease in one-third or less of the cases.3'5 Cardiac malfunction and resultant manifestations, including pulmonary edema, are covered in chapter 2. The primary cause of pulmonary edema is overhydration in the face of decreased renal function associated with rejection or posttransplant acute tubular necrosis.3 Other etiologies include sepsis, pancreatitis, fat embolism, aspiration, cerebral edema, drug reaction, and oxygen toxicity.7'22'23 Pulmonary edema most commonly develops in the immediate postoperative period and the early intermediate period (1-2 months),3 when the incidence of rejection and other significant graft malfunctions is maximal. Patients with decreased renal function and pulmonary edema almost all have a low-grade fever. Usually, however, other clinical symptoms will help to differentiate pulmonary edema from infection. Weight gain and hypertension, especially in the presence of rejection, are much more prevalent with pulmonary edema;3 and fever usually follows any decrease in renal function instead of preceding it, as happens with infection—especially cytomegalovirus, or cytomegalovirus with Pneumocystis.328 The severity of cough as a symptom is out of proportion to dyspnea in patients with pulmonary edema,5 whereas in Pneumocystis infections, the dyspnea is more severe. Pulmonary edema can probably be excluded from the differential diagnosis if cardiac and renal function are normal.21 Factors associated with an increased risk of pulmonary edema include older age, elevated creatinine, poor antigen match, and a cadaver kidney. 7 As with all noninfectious complications, when pulmonary edema is complicated by superinfection the mortality rate is very high, up to 100%.5 Radiologically, pulmonary edema may be indistinguishable from infection (fig. 3.12). Those characteristics that, if present, help to establish a diagnosis of pulmonary edema include engorged vasculature, especially in the upper lobes; cardiomegaly; and signs of interstitial edema, such as Kerley's lines and bilateral effusions (figs. 3.13 and 3.14).5'7 The alveolar component of pulmonary edema


37

Figure 3.12. Pulmonary edema presenting as a unilateral effusion and "pseudomass."

Figure 3.13. Pulmonary edema (B) in a patient with sudden transplant renal failure who had a normal chest X-ray

(A) 1 6 days earlier at the beginning of a rejection episode.

Figure 3.14. Pulmonary edema (B) in a patient with renal failure due to rejection. Normal chest (A } 1 2 hours earlier.

Pulmonary edema resulted from fluid overload during surgery. A proper balance is very difficult to maintain.

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Hunter and Crass

may be patchy and bibasilar but is usually central or perihilar.5'23 The alveolar infiltrate of infection is usually peripheral, the only exceptions being cytomegalovirus and Pneumocystis. Infection and pulmonary edema both develop rapidly; but pulmonary edema will respond much more rapidly to treatment, with significant clearing possible in 24-48 hours (fig. 3.3). Pulmonary embolism Pulmonary embolism has been the second most frequent cause of death in transplant patients in past reports.33 Sudden cardiac death may have displaced it recently,24 but embolism remains an important problem because of the high associated mortality. Pulmonary embolism most often occurs in the immediate postoperative period,3'5'33 but it is not uncommon in the early intermediate period.5'33 It is rare after 12 months.33 In a study by Simmons et al.,3 three of six patients with pulmonary embolism had thrombophlebitis, and all thrombophlebitic patients had clinical or subclinical evidence of pulmonary embolism. Ramsey et al.,5 however, had no patients with pulmonary embolism who had evidence of thrombophlebitis. In yet another study,16 five of the deaths attributed to pulmonary embolism showed the source of the thrombus to be in ileo-femoral or popliteal veins. Possible causes of thrombophlebitis include postoperative inactivity; extrinsic stimulation of coagulation by antigen-antibody complexes, microbes, or endotoxins; hyperlipidemia; and a hypercoagulability that results from overcorrection after transplantation of the coagulation abnormalities of uremia.33 Very few patients with pulmonary embolism have all the classical clinical symptoms, and the problem may therefore be significantly underdiagnosed.3 Nonetheless, the history and clinical findings can be helpful because the onset of symptoms is abrupt; in one series,5 five of nine patients did have dyspnea, cough, and hemoptysis, and three of nine had pleuritic pain. The diagnosis of pulmonary embolism is difficult because radiologic findings are minimal or absent33 until infection supervenes, at which point the mortality rate is very high —90% or greater.33 Secondary infection is most commonly seen in those patients who suffer a pulmonary embolism in a period following transplant rejection and high-dose corticosteroid therapy.5 The most common radiologic picture is one of patchy, peripheral, alveolar infiltrates5'7 reflecting the prevalence of multiple emboli per embolization episode.


39

Septic emboli usually have a different appearance, with multiple, moderate-sized nodules or patchy infiltrates 21 that commonly cavitate (fig. 3.15). 7 The clinical and radiologic picture of bland or septic emboli can be imitated by certain fungal infections, especially by Phycomycetes and Asperg///us, which invade and obstruct pulmonary vessels.17 Figure 3.15. Septic emboli presenting as multiple bilateral nodules, one of which (arrow] appears to be cavitating.

Pulmonary Hemorrhage Pulmonary hemmorrhage, which is uncommon after transplantation, is rarely diagnosed before death.7 It is more common in uremic patients with chronic renal failure. 7 When pulmonary hemorrhage occurs in a transplant patient, it is most commonly seen in the intermediate period (2 weeks to 4 months) when problems with the transplant and infection are also at a maximum. The postulated cause of hemorrhage is thrombocytopenia as part of generalized marrow suppression due to immunosuppressive therapy, especially azathioprine.7'14 The X-ray picture is identical to pulmonary edema, with prominent interstitial markings and diffuse alveolar infiltrates that are more pronounced in the central regions.7'14 Malignancy The incidence of malignant disease is much greater following transplantation than in the general population, and this incidence increases steadily with time.33"38 Most malignancy occurs more than 2 years after transplantation,34'36 with lymphomas occurring earlier than other types of cancer. 36 Some carcinomas may arise because of chronic allogenic stimulation and an altered immune status,33-36-38

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others may be coincidental, and some may unknowingly be transmitted with the donated kidney. Although tumor incidence does not appear to be related to graft function, there is disagreement as to whether the incidence is increased in patients with a poor antigen match. It is also unclear whether viral activation (especially of herpesvirus) or mutagenic drugs such as azathioprine 22 may play a part in oncogenesis. The overall incidence of malignancy in patientson dialysis iseven higher than in the transplant group. The incidence of lung tumors, however, is lower in patients on dialysis than in either the transplant or normal population.35 Although most of the tumors occurring in transplant patients are low grade and can be temporarily controlled with chemotherapy, the short-term follow-up mortality that has been reported has been a very high 80-100%,34'37 with two-thirds of the deaths directly attributable to the tumor. 34 The most common type of malignancy is lymphoma,34'36'38 with much lower incidences of primary lung carcinoma and carcinoma metastatic to the lung (fig. 3.16). Lymphoma usually arises in the skin or central nervous system, but lung lesions do occur. Reports of malignancy are increasing as transplant patients survive longer.16 Several cases of Kaposi's sarcoma, as in the acquired immune deficiency syndrome, have already been reported.36 The most common radiologic appearance of lung carcinoma (fig. 3.17) and posttransplant lymphoma (figs. 3.18 and 3.19) at the University of Minnesota has been multiple parenchymal nodular densities without hilar adenopathy. Most tumors are discovered on routine chest X-rays prior to the development of symptoms. 34 Others are discovered as hidden nodules that appear following treatment of pneumonia (fig. 3.20). 38 Figure 3.16. Widely metastatic, aggressive, immunoblastic sarcoma with greatly enlarged bilateral hilar nodes.


41

Figure 3.17. Adenocarcinoma presenting as a solitary nodule in an asymptomatic patient 10 years following transplantation.

Figure 3.18. Lymphoma presenting as multiple, bilateral, moderate- to largesized nodular densities.

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Figure 3.79. Lytnphoma presenting as multiple, bilateral, small to moderate-

Figure 3.20. Endobronchial carcmoma presenting as a right lower lobe staphylococcal pneumonia, alveolar infiltrate on the PA (A) and lateral (B) films. Following resolution of the pneumonia the nodular density of the remaining tumor (arrow) persists (C).

sized nodular densities (A, PA film; B, lateral film).


43

Soft Tissue Calcification Pulmonary soft tissue calcification is infrequent and usually asymptomatic.39 It is secondary to metabolic changes associated with chronically impaired renal function rather than a complication of transplantation or immunosuppressive therapy.22 In one autopsy series, it was found in 9 of 15 chronic renal failure patients.40 Most cases of pulmonary calcification are microscopic, either not visible on a plain chest X-ray or appearing as a noncalcified peripheral interstitial infiltrate.22'40 Computed tomography or radioisotope scanning might be more accurate methods of detection. Most pulmonary metastatic calcification is now discovered at biopsy or autopsy as deposits in the walls of bronchioles, arteries, and alveoli.39'41 Calcium deposits that have been described on chest X-ray range from punctate to large, wedge-shaped collections that regressed dramatically with improvement in renal status.22 Mediastinal Lipomatosis Mediastinal lipomatosis is a common finding in patients undergoing long-term corticosteroid therapy. The plain chest X-ray appearance is a smoothly marginated, soft-tissue density in the mediastinum. The important differential diagnostic consideration is amediastinal malignancy. This question can be answered easily and definitively today by computed tomography, on which the lower fat density of lipomatosis can be clearly distinguished from the soft-tissue density of tumor and normal tissue. latrogenic Complications Complicationsof needle or open-lung biopsy include pneumothorax, bronchopleural fistula, and hemorrhage. Resuscitative efforts can cause pulmonary contusion. The radiologic appearance of these problems is not different in the transplant population. Drug reactions, although uncommon, do occur. Azathioprine has been implicated as a cause of pulmonary disease in one patient.5 Other cases of possible reactions to blood products, antilymphocyte globulin, and antibiotics (especially furantoin) have been seen.

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Pleural Effusion/Pleuritis Following transplantation, pleural effusion is associated either with infection (in which case it likely represents an empyema) or pulmonary edema.5'10 Unilateral effusion is equally likely to be caused by infection or pulmonary edema.7 Bilateral effusions, however, imply an element of pulmonary edema even in those patients who also have an infection.7 Pleural effusion associated with infection is most commonly seen with the gram-negative organisms, staphylococcus, and Nocardia.5'1 The "empyema" effusion is usually larger than the effusion associated with pulmonary edema. A "fibrinous" pleuritis occurs in uremic patients. Twenty percent of uremic patients with pleuritic symptoms have a demonstrable effusion.22

REFERENCES 1. Howard RJ, Simmons RL, Najarian JS: Fungal infections in renal transplant patients. Ann Surg 188:598-605,1978. 2. Pechan WB, Novick AC, Lalli A, Gephardt G: Pulmonary nodules in a renal transplant recipient. J Urol 124:111-114, 1980. 3. Simmons RL, Uranga VM, LaPlante ES, Buselmeier TJ, Kjellstrand CM, Najarian JS: Pulmonary complications in transplant recipients. Arch Surg 105:260-268, 1972. 4. Stake G, Flatmark A: Lung complications during immunosuppressive treatment in renal transplant recipients. Scand J Resp Dis 57:51-62, 1976. 5. Ramsey PG, Rubin RH, Tolkoff-Rubin NE, Cosimi AB, Russell PS, Greene R: The renal transplant patient with fever and pulmonary infiltrates: Etiology, clinical manifestations, and management. Med 59:206-22, 1 980. 6. Rubin RH, Wolfson JS, Cosimi AB, Tolkoff-Rubin NE: Infection in the renal transplant recipient. Am J Med 70:405-411, 1981. 7. Webb WR, Gamsu G, Rohlfing BM, et al.: Pulmonary complications of renal transplantation: A survey of patients treated by low-dose immunosuppression. Radiology 126:1-8, 1978. 8. Wiggers RH: Pulmonary complications after renal transplantation (radiological aspects). Radiologia Clin 47:44-57, 1978. 9. Mattson K, Edgren J, Kuhlba'ck B: Pulmonary infections after renal transplantation. Ann Clin Res 11:63-65, 1979. 10. Huertas VE, Port FK, Rozas VV, Neiderhuber JF: Pneumonia in recipients of renal allografts. Arch Surg 111:162-166, 1976. 11. Munda R, Alexander JW, First MR, Gartside PS, Fidler JP: Pulmonary infection in renal transplant recipients. Ann Surg 1 87:1 26-1 33, 1 978. 12. Taylor RJ, Schwentker FN, Hakala TR: Opportunistic lung infections in renal transplant patients: A comparison of Pittsburgh pneumonia agent and legionnaires disease. J Urol 125:289-292, 1981. 13. Williams DM, Krick JA, Remington JS: Pulmonary infection in the compromised host, part I. Am Rev Respir Dis 114:359-394, 1976.


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14. Nelson J, Bragg DG, Armstrong JD, Jr.: Cardiopulmonary complications of renal transplantation. Semin Roentgenol 13:311 -318,1978. 15. Lee DBN, Prompt CA, Upham AT, Kleeman CR: Medical complications in renal transplantation: I. Graft and infectious complications in recipients. Urology (Suppl) 9:7-31,1977. 16. Miller JB, Hanto DW, Sutherland DER, Simmons RL, Najarian JS: Increase in nonseptic causes of death after renal transplantation. Department of Surgery, University of Minnesota, Minneapolis, 1983. 17. Blank N, Castellino RA, Shah V: Radiographic aspects of pulmonary infection in patients with altered immunity. Rad Clin North Am 11:1 75-190, 1 973. 18. McWhinney N, Khan O, Williams G: Tuberculosis in patients undergoing maintenance hemodialysis and renal transplantation. Br J Surg 68:408-411, 1 981. 19. Coutts II, Jegarajah S, Stark JE: Tuberculosis in renal transplant recipients. Br J Dis Chest 73:141-148, 1979. 20. Voz AJ: Miliary tuberculosis and the adult respiratory distress syndrome in a renal transplant recipient. (Letter) Chest 75:412, 1979. 21. Goodman N, Daves ML, Rifkind D: Pulmonary roentgen findings following renal transplantation. Radiology 89:621-625, 1967. 22. Schwartz EE, Onesti G: The cardiopulmonary manifestations of uremia and renal transplantation. Rad Clin North Am 10:569-581, 1972. 23. Freundlich IM: Diffuse Pulmonary Disease. Philadelphia: WB Saunders, 1 979. 24. Stevens DA, Pier AC, Beamen BL, Morozumi PA, Lovell IS, Houang ET: Laboratory evaluation of an outbreak of nocardiosis in immunocompromised hosts. Am J Med 71:928-934, 1981. 25. Bragg DG, Janis B: The roentgenographic manifestations of pulmonary opportunistic infections. AJR 117:798-809, 1973. 26. Bode FR, Pare JAP, Eraser RG: Pulmonary diseases in the compromised host. Med 53:255-293, 1974. 27. Davies SF, Sarosi GA, Peterson PK, et al.: Disseminated histoplasmosis in renal transplant recipients. Am J Surg 137:686-691, 1979. 28. Hamed IA, Wenzl JE, Leonard JC, Altshuler GP, Pederson JA: Pulmonary cytomegalovirus infection: Detection by gallium 67' imaging in the transplant patient. Arch Intern Med 139:286-288, 1979. 29. Rubin RH, Russell PS, Levin M, Cohen C: Summary of a workshop on cytomegalovirus infections during organ transplantation. J Infect Dis 139:728-734, 1 979. 30. Scoggin CH, Call NB: Acute respiratory failure due to disseminated Strongyloides in a renal transplant recipient. (Letter) Ann Intern Med 87:456-458, 1 977. 31. Venizelos PC, Lopata M, Bardawil WA, Sharp JT: Respiratory failure due toStrongyloides stercoralis in a patient with a renal transplant. Chest 78:104-106, 1980. 32. Weller IVD, Copland P, Gabriel R: Strongyloides stercoralis infection in renal transplant recipients. Br Med J (Clin Res) 282:524, 1981. 33. Birkeland SA, Kemp E, Hauge M: Cancer as a late-onset complication of kidney transplantation. Scand J Uroi Nephrol (Suppl) 42:179-183, 1977. 34. Fjelborg O, Olsen S, Posborg V: Malignant tumors in the Aarhus transplant series. Scand J Urol Nephrol (Suppl) 42:184-185, 1977. 35. Jacobs C, Brunner FP, Brynger H, et al.: Malignant disease in patients treated by dialysis and transplantation in Europe. Transplant Proc 1 3 (I Pt l):729-732, 1981. 36. Penn I: Malignant lymphomas in organ transplant recipients. Transplant Proc 13(1 Pt l):736-738,1981. 37. Sheil AGR, Mahoney JF, Horvath JS, et al.: Cancer following successful cadaveric donor renal transplantation. Transplant Proc 13(1 Pt l):733-735, 1981. 38. Thiru S, Calne RY, Nagington J: Lymphoma in renal allograft patients treated with cyclosporin-A as one of the immunosuppressive agents. Transplant Proc 13(1 Pt I): 359-364, 1981.

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39. Giacobetti R, Feldman SA, Ivanovich P, Huang CM, Levin ML: Sudden fatal pulmonary calcification following renal transplantation. Nephron 19:295-300, 1977. 40. Gilman M, Nissim J, Terry P, Whelton A: Metastatic pulmonary calcification in the renal transplant recipient. Am Rev Respir Dis 121:415-419, 1980. 41. Conger JD, Hammond WS, Alfrey AC, Contiguglia SR, Stanford RE, Huffer WE: pulmonary calcification in chronic dialysis patients. Ann Intern Med 83:330-336, 1975.

CHAPTER 4

Evaluation of Gastrointestinal Complications Mathis P. Frick and Susan Roux

Patients with end-stage renal disease who are treated by renal allografts may experience complications not related to renal function. Besides the immediate surgical complications of hemorrhage, vascular thrombosis, ureteral leak, and wound infection, problems related to other organ systems are seen. These problems may be so severe that they are fatal even when the renal transplant functions well. Gastrointestinal tract complications figure prominently in the outcome of renal transplantation, representing hazards that require close surveillance of the patient's complaints, however minor. These complications involve all segments of the gastrointestinal tract and all intra-abdominal organ systems.1"17 Gastrointestinal complications following renal transplant are reported to occur in about 10% of cases, with a mortality rate of 23-35% (table 4.1 ).6,i2,i3,i6,i8,i9^o The most common intra-abdominal complications are peptic ulceration with hemorrhage, hepatitis, intestinal obstruction, and pancreatitis.1'11 Less common complications are colonic perforation,

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Frick and Roux Table 4.1. Reported Incidence and Mortality of Gastrointestinal Complications Authors

Number of Patients

Faro and Corry, 1979 1 * Hadjiyannakisetal., 1971 19 Julienetal., 1975 6 Meechetal., 197912 Meyers etal., 1979 13 Owens etal., 197614 Rosekrans, 1978 16 Schnyderetal., 1979 20

265 139 510 290 141 109 110 85

Incidence 7.2% 23 6 6.6 37 34 20 16

Mortality 16% 44 45 42 -

27 41 7

ischemicnecrosis,and lowergastrointestinal bleeding.1-4'5'7'10'15'16'19'21 Upper gastrointestinal bleeding should be regarded as the principal complication that, particularly in combination with liver failure due to HAA-positive hepatitis, often leads to death.1'3'9'11'14'16 Factors contributing to gastrointestinal complications include long periods of dialysis and chronic uremia before transplantation, hyperparathyroidism, cytomegalovirus infection, abdominal surgery, and high doses of immunosuppressive drugs.20 Steroids are notable because they may mask clinical symptoms, thus delaying the diagnosis.22'23 Most of the serious complications —particularly upper gastrointestinal hemorrhage and nondiverticular intestinal perforations — occur within 6 months of transplantation, often during episodes of rejection.12'13 Although an uneventful course during the first 6 months following transplantation usually favors successful continuation, fatal complications may occur many months later.7'23 Pancreatitis, diverticulitis, and gastroduodenal perforation usually occur late in long-term survivors with well-functioning allographs.13'23 Complications also follow renal transplantation in children, although the mortality rate is considerably lower. The incident rate is approximately 16%, with mortality of 7%.20 Complications include small bowel obstruction, gastroduodenal ulceration, pancreatitis, hepatitis, ascites, and severe gastroenteritis. The absence of atherosclerotic vascular diesease in this age group may improve survival. The high morbidity and mortality rates of abdominal complications warrant vigorous diagnostic evaluation of even minor clinical, laboratory, and radiographic abnormalities. The radiologic workup may include plain radiography of the abdomen, contrast studies,

Gastrointestinal Complications

49

abdominal sonography, computed tomography (CT), and angiography.6'10'23

ALIMENTARY TRACT COMPLICATIONS Esophagitis Transplant patients with esophageal disorders often present with retrosternal pain or dysphagia, symptoms that are usually caused by monilial, viral, or reflux esophagitis. Esophageal varices are occasionally seen in the transplant recipient. 24 Monilial esophagitis (figure 4.1) is the most common infection of the esophagus in transplant patients.23'25-26 The normally saprophytic microorganism Candida albicans can develop invasive properties in the presence of the reduced humoral and cellular resistance commonly encountered during immunosuppressive therapy. From the oropharyngeal cavity where yeast is normally found, the infection may spread to the esophagus.16 The principal radiologic features of monilial esophagitis include loss of normal esophageal peristalsis, narrowed lumen secondary to mucosal swelling with resultant granular surface, and "cobblestoning" or nodular filling defects of various sizes.25 Ulceration and small mucosal defects are also noted. Smaller mucosal defects represent white plaques noted on endoscopy, whereas larger ones result from pseudomembranes of necrotic debris.25 Severe monilial esophagitis may show deeply ulcerated mucosa. Repeat esophagrams following treatment demonstrate a return to normal, but stricture formation occurs occasionally. 23 ' 26 Esophagitis resulting from herpes simplex virus or cytomegalovirus infections are often indistinguishable from monilial disease. Characteristic plaquelike filling defects or superficial ulcerations are observed on esophagrams. Patients with viral esophagitis are often asymptomatic, and findings on esophagrams frequently disappear within a few days.25 Although reflux esophagitis in allograft recipients may be incapacitating, it usually does not constitute a serious complication. 23 Radiologic findings on esophagrams are often absent, but reflux or stricture formation are occasionally demonstrated.14'15 Esophageal varices may occur in renal transplant patients who have chronic liver disease, typically after long-term graft survival in the absence of significant rejection. 24

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Figure 4.1. Monilial esophagitis in 32year-old renal transplant patient. Note ulceration (small arrow], mucosal irregularities, and filling defects representing plaques and necrotic debris (large arrow).

Gastrointestinal Hemorrhage Gastrointestinal hemorrhage presenting as hematemesis or melena is the most common clinically significant problem in transplant patients.4'13'27 Peptic ulcer disease, erosive gastritis, and cecal ulcers are the most common causes of massive, often fatal hemorrhage in renal transplant patients.1'3'6'8'10'12'14'16'17'19-23'28"36 In a review by Owens et al.,34 more than half of the patients with peptic ulceration presented with hemorrhage. Bleeding was seen more commonly with duodenal ulceration, whereas gastric ulcers were often associated with perforation (fig. 4.2). Mortality rates ranging from 50 to 75% are reported, accounting for two-thirds of all deaths related to gastrointestinal complications in allograft recipients. Several factors may influence the occurrence of mucosa breakdown in the posttransplant period. Persistence of hyperparathyroidism predisposes to ulceration and hemorrhage. Increased calcium levels stimulate hydrochloric acid secretion through increased gastrin production.36 Uremia, by altering the gastric mucosal barrier and producing coagulation abnormalities, can aggravate ulceration and hemorrhage. Corticosteroids also reduce the resistance of the intestinal epithelium to the action of digestive enzymes. Although steroids have not been shown to have a locally erosive effect, they


57

Figure 4.2. Hematemesis in 25-year-old renal transplant patient. Upper gastrointestinal study using water-soluble contrast shows prominent rugal folds and antral ulcer (arrow).

have an unfavorable influence on the regeneration of connective tissue.19 Nephrotic patients on steroid therapy show an increased incidence of ulcers when compared with controls. Hypoalbuminemia may lead to decreased protein binding of steroids and higher free-drug concentrations, thus increasing the risk of ulcer formation in posttransplant patients.36'37 Clinical symptoms of ulceration are often masked by steroid therapy, resulting in delay in diagnosis. Early and careful radiologic evaluation is justified by an awareness that subtle clinical and radiologic signs may be the only clues to impending serious complications. Generalized cytomegalovirus infection is often associated with gastrointestinal bleeding.3'32 Cytomegalovirus infections are reactivated, sometimes with fatal consequences, in 60-90% of renal transplant recipients after initiation of immunosuppressive therapy. In recent years, cytomegalovirus-induced colonic ulcers have been recognized as the most important cause of severe lower gastrointestinal bleeding in these patients.38 Although the gastrointestinal involvement may be an isolated manifestation, cytomegalovirus is usually disseminated to the lungs, adrenals, liver, gastrointestinal tract, pancreas, and kidneys.39'40 Vasculitis associated with cytomegalovirus infection is the precursor of mucosal erosions and ulceration. Clinically, cytomegalovirus infection often has a hemorrhagic component manifested by the presence of petechiae, purpura, and thrombocytopenia. In the diagnostic evaluation of massive gastrointestinal hemorrhage in renal transplant patients, gastroduodenoscopy and angiography are the methods of choice.21'23'36 Angiography offers both diagnostic and therapeutic benefits, including vasopressor treatment and catheter embolization. In addition, radionuclide studies

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may be helpful for screening prior to angiography. Barium studies and colonoscopy are of less value. Barium administration may further interfere with subsequent angiography.15'23 Bleeding from the upper gastrointestinal tract occurs in about 7% of all renal transplant patients,41 usually within 6 months of allograft transplantation. It often occurs in relation to antirejection therapy.15'28 Recipients of grafts from living relatives appear to be less susceptible to this complication than recipients of cadaver kidneys.1'14 The value of pretransplant prophylactic surgery (vagotomy and antrectomy/pyloroplasty)13'34'36'41'42 and the value of cimetidine in prevention of posttransplant gastroduodenal ulceration is disputed.43~4S Erosive gastritis causing bleeding, which is easily recognized in the early period after transplantation, is the most common cause of upper gastrointestinal hemorrhage.23'46 Diagnosis is suggested by bleeding in an asymptomatic or mildly symptomatic patient. It can usually be verified by gastroscopy.23 Radiologic examination for upper gastrointestinal hemorrhage demonstrates various complications.8"16'23'28'47 Superficial ulcerations are usually accompanied by the coarsening of mucosal folds in stomach and duodenum.15 In addition, hypertrophy of Brunner's glands has been identified in these patients. Gastroduodenal ulcers in transplant patients are radiographically similar to those occurring in the general population (fig. 4.2), but a relative increase in frequency of gastric ulcers over duodenal ulcers has been noted.23 Some are associated with cytomegalovirus infections. However, duodenal ulceration remains the most commonly demonstrated abnormality in gastrointestinal hemorrhage following transplantation.15 Bloody diarrhea is frequently reported in the renal allograft recipient. The source is usually the colon, and numerous etiologies have been identified. Superficial ulcerations in the large bowel are a significant source of major hemorrhage in these patients.23'36'39 Hemorrhoids, extensive submucosal colonic hemorrhage, diverticulosis, polyps, and candidiasis of the colon are less common causes of lower gastrointestinal hemorrhage in renal transplant patients.13'48-49 Bleeding cecal ulcers (fig. 4.3) associated with cytomegalovirus infections occur in 12% of renal transplant patients and carry a particularly grave prognosis,23'32'36'39 with a mortality of 80%.32-36'39 In transplant recipients with mucocutaneous vascular lesions, Kaposi's sarcoma should be considered as a rare cause of lower gastrointestinal hemorrhage.47'50


Figure 4.3. (A, B) Massive lower gastrointestinal bleeding in 30-year-old renal transplant patient due to cecal ulcerations associated with cytomegalovirus infec-

53

tion. Angiogram of the superior mesentery artery shows extravasation and puddling of contrast medium in the right lower quadrant (arrows).

Bowel Obstruction In the early posttransplant period, differentiation of postoperative ileus from mechanical bowel obstruction may be difficult. 23 A hypomotility syndrome after renal transplantation may prolongpostoperative ileus and precipitate fecal impaction, especially in diabetic patients.6 Nonabsorbable antacids have been shown to cause fecal impaction, often involving the right colon and small bowel. 6 ' 51 " 53 Severe fecal impaction may lead to bowel necrosis and perforation.23 Water-soluble contrast enemas offer both diagnostic and therapeutic benefits to the patient with fecal impaction.54 Adhesions are the most common cause of mechanical small bowel obstruction.6'55 Uremia, peritoneal dialysis, and splenectomy all contribute to the increased incidence of adhesions in these patients.6 External and internal hernias and volvulus are also causes of mechanical small bowel obstruction in the transplant patient.6'56 The "paratransplant" hernia, caused by entrapment of bowel or omentum through a defect in the peritoneal covering of the renal transplant, has been reported as a rare cause of mechanical small bowel obstruction. 57 Plain abdominal radiographs at regular intervals are essential in the diagnostic evaluation of posttransplant patients because immunosuppression tends to mask clinical findings of mechanical obstruction.6'23 If bowel obstruction is suspected, water-soluble contrast enemas are indicated. The high mortality

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rate associated with peritonitis in renal transplant patients warrants prompt surgical relief of intestinal obstruction to avoid small bowel perforation.57 Bowel Perforation Perforation of the large or small bowel is a relatively common and frequently fatal complication of the transplant recipient.2'6'19'23' 58-63 Mortality has been reported at 80%.8'23>64 There is an unusually high incidence of ileal and colonic perforation in renal transplant patients, with an incidence rate of approximately 2-4%.2'23' 62,65,66 j\/|any C olonic perforations have been associated with diverticular disease (fig. 4.41.2,23,28,51,62,64,67,68 Free perforation of diverticulitis appears related to immunosuppression.17 In patients on steroid therapy, the increased occurrence of diverticulitis may be due to the atrophy of the intestinal lymphoid collections and secondary diminished resistance to bacterial invasion.67'69 When diverticulitis does occur, it is probable that perforations are less successfully walled off, resulting in generalized peritonitis. Ileal colonic perforations have also been shown to be associated with

Figure 4.4. A 47-year-old patient developed fever, abdominal pain, and distention as well as pneumoperitoneum (A) 3 weeks after renal transplantation. Enema using water-soluble contrast showed a perforated sigmoid colon probably as-

sociated with a diverticulum (B, arrow}. Note extravasation of contrast medium into paracolic gutter and subhepatic space. Laparotomy confirmed the diagnosis of diverticulitis with free perforation.


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fecal impaction, placement of peritoneal dialysis catheters, and ischemic and infectious colitis.6'15'18-19-23'31'51'53'56'60'61'63"65'70'71 Duoedenal ulcers, the most common cause of upper gastrointestinal perforation, may occur in long-term survivors with well-functioning renal allografts. (fig. 4.5).7,11,13,14,16,19,23,35,72 The clinical presentation of intestinal perforation in renal transplant recipients may include abdominal distension, pain, paralytic ileus, fever, and systemic sepsis.61'73 However, there may be few physical signs and symptoms secondary to the use of steroids. Radiographic studies may offer the only evidence of bowel perforations.6'23 Plain radiographs of the abdomen should be obtained in various projections, including the left lateral decubitus.74 A careful search for pneumoperitoneum orextraluminal gas associated with an abscess is essential (fig. 4.5).23 Absence of free peritoneal air on plain radiography, however, does not exclude a perforated viscus. The prompt use of an enema with water-soluble contrast is necessary when there is unexplained abdominal pain in a patient who has undergone renal transplantation (fig. 4.4).23 Since perforation preferentially involves the lower intestinal tract, the enema should precede the upper gastrointestinal series unless there is a history of previous ulcer disease (fig. 4.5).23'75 Laparotomy confirms the diagnosis and is usually followed by resection of the diseased bowel.

Figure 4.5. A 25-year-old transplant patient with previous history of ulcer disease developed abdominal pain and distention. Abdominal plain radiograph (A) shows paralytic ileus and pneumoperito-

neum. Upper gastrointestinal series using water-soluble contrast (B) shows free perforation associated with duodenal ulcer (arrows).

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Ischemic Bowel Disease Preoperative diagnosis of intestinal infarction in renal transplant patients is difficult.6'8'23'76 Clinical symptoms may include abdominal pain and tenderness, fever, nausea, vomiting, melena, and loss of bowel sounds.8'76 Mortality is high, especially if bowel infarction is associated with perforation.6'27 Plain radiographs of the abdomen are characterized by adynamic ileus with or without pneurmatosis intestinalis or pneumoperitoneum.8 Prolonged postoperative ileus is suspicious of bowel infarction, especially if intramural air is present.6 Water-soluble contrast enemas may demonstrate mucosal ulcerations; classic "thumbprinting," sawtoothed irregularity of mucosa; and pseudopolypoid filling defects due to intramural hemorrhage.8 Uncommon Alimentary Tract Complications The gastrointestinal tract is the site of multiple problems that occur less often than those described earlier. These include pseudomembranous enterocolitis,8'15'56'60 intraabdominal abscess and peritonitis without perforation.3'6'64 pneumatosis cystoidis intestinalis,6 and acute appendicitis. 8 ' 65 ' 77 Findings of acute appendicitis can be mimicked by infarction of the renal allograft,77 although this is rare. Candidiasis of the duodenum and jejunum have been documented at autopsy in 20% of renal transplant recipients.78 Upper gastrointestinal series may show prominent mucosal folds in the duodenum —a nonspecific finding. Associated changes in the esophagus are usually characteristic, as described earlier. Finally, unusual positioning of the renal transplant in the iliac fossa may mimic a pelvic mass (fig. 4.6).

PANCREATIC COMPLICATIONS Pancreatitis has been reported in 2-6% of all allograft recipients, with a mortality of 50-100%.1'6'8'10'11'18'23'31'35-79-81 It may occur anytime after renal transplantation, but it is seen characteristically in long-term survivors with well-functioning allografts.13 Several factors may predispose a renal transplant recipient to the development of acute pancreatitis. Corticosteroids have been known to be associated with pancreatitis both in experimental animals and


57

Figure 4.6. Renal transplant in unusual location (A: tomogram) mimicking pelvic mass on barium enema (B).

man.79 Hypercalcemia from hyperparathyroidism may induce pancreatitis by facilitating conversion of trypsinogen to trypsin in the pancreas. Surgical trauma to the pancreas at the time of pretransplant nephrectomy or other surgery is also important. Autoimmune factors related to rejection, including cross-reactions of antigens between graft and pancreas, have also been studied.79 Viral etiology, especially cytomegalovirus, is also important. The cytomegalovirus has been identified and cultured from pancreatic tissue in renal transplant patients with pancreatitis. 79 Additional factors may include the toxic effects of uremia, ethanol abuse, and presence of biliary tract disease. Early diagnosis and prompt treatment are essential for survival of renal transplant patients with pancreatitis.23 Clinical diagnosis is often difficult because symptoms are obscured by steroid therapy. Radiographic features of pancreatitis in transplant recipients are not different from those of nontransplanted patients.23 Plain radiographs of the abdomen may reveal a sentinal loop, the "colon cut off" sign, and pancreatic calcifications. Chest radiographs may demonstrate elevated left hemidiaphragm and pleural effusions.8'16'17 An upper gastrointestinal barium study may show widening, prominent rugal folds and mucosal edema of the duodenal sweep. Feared complications of pancreatitis in renal transplant patients include hemorrhage, plegmon, abscess, and pseudocysts. 23 These are best evaluated by CT or abdominal sonography.82 Pseudocysts and abscesses are amenable to percutaneous aspiration biopsy and drainage guided by CT or ultrasound

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Figure 4.7. Pancreatitis in 34-year-old renal transplant patient. Note peripancreatic edema and large pseudocyst near the pancreatic tail ( A ) . The latter was successfully drained using aspiration biopsy guided by computed tomography and catheter placement (B, C).

(fig. 4.7).83 Rarely, a pseudocyst may drain spontaneously by forming a pancreaticoduodenal fistula.84

HEPATOBILIARY

COMPLICATIONS

Hepatic dysfunction and hepatitis occur in 7-60% of renal transplant patients. The etiology remains uncertain, although viral hepatitis, cytomegalovirus infection, and various drugs are often suspected.8'16 Most infections are HAA positive, and the cause must therefore be sought in the many transfusions that the patients receive in the course of the illness, including the period of intermittent hemodialysis preceding transplantation. Chronic liver failure, portal hypertension, and esophageal varices may occur in long-term survivors. 24 Cholecystitis with or without cholelithiasis is often difficult to diagnose in a patient on steroid therapy.6'22 Sonography is the initial radiographic modality of choice.


59

ABDOMINAL MALIGNANCY AFTER RENAL TRANSPLANTATION There is an increased incidence of epithelial and lymphoproliferative neoplasms in renal transplant patients compared with the general population.8S~87 Gastrointestinal malignancies that have been associated with renal transplantation include gastric carcinoma;17 ileal carcinoma;55'87 extramedullary intestinal plasmocytoma;88 Kaposi's sarcoma;50 and, most importantly, reticulum-cell sarcomas (immunoblastomas) of stomach, small bowel and colon.44'75-89"91 Lymphoproliferative disorders after renal transplantation show very atypical biologic behavior and radiographic appearance (fig. 4.8).89'92

Figure 4.8. Posttransplant lymphoma (immunoblastic sarcoma) in 67-year-old renal transplant patient. The tumor extensively infiltrated fatty and connective tissue and showed large zones of necrosis. Computed tomography (A) and sonography (B) showed an intraabdominal

mass. The posttransplant lymphoma (arrows) was characterized on computed tomography by a central area of low attenuation probably representing necrosis and on ultrasound by inhomogenous intrinsic echo pattern. (Transplant kidney = R.) (From Tubman, DE, Frick, MP, Hanto, DW: Radiology 149:625-631, 1983. Reprinted by permission.)

REFERENCES 1. Aldrete JS, Sterling WA, Hathaway BW, et al.: Gastrointestinal hepatic complications affecting patients with renal allografts. Am J Surg 1 29:115-124,1975. 2. Carson SD, Krom RA, Uchida K, etal.: Colon perforation after kidney transplantation. Ann Surg 188:109-113, 1978. 3. Diethelm AG, Gore I, Chien LT, et al.: Gastrointestinal hemorrhage secondary to cytomegalovirus after renal transplantation: A case report and review of the problem. Am J Surg 131:371-374, 1976. 4. Griffith HJ: Radiology of renal failure. WB Sanders, Philadelphia, pp. 156-177, 1976. 5. Hubbard SG, Bivins BA, Lucas BA,et al.: Acute abdomen in the transplant patient. Am Surg 46:116-120, 1980.

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6. Julien PJ, Goldberg HI, Margulis AR, et al.: Gastrointestinal complications following renal transplantation. Radiology 11 7:37-43, 1975. 7. Kuhlback B, Lilius P.: Late complications after primarily successful renal transplantation. Acta Med Scand 200:21-24, 1976. 8. Lee HM, Madge GE, Mendez-Picon G, et al.: Surgical complications in renal transplant recipients. Surg Clin. North Am 58:285-304, 1978. 9. Lerut J, Lerut T, Gruwez JA, et al.: Surgical gastrointestinal complications in 277 renal transplantations. Acta Clin Belg 79:383-389, 1980. 10. Libetino J A , Zinman L, Dowd JB, Braasch SW: Gastrointestinal complications related to human renal homotransplantation. Surg Clin North Am 51:733-757, 1 971. 11. Lindstrom BL, Lindfors O, Eklund B, et al.: Surgical complications in 500 kidney transplantations. Proc Eur Dial Transplant Assoc 14:353-361, 1 977. 12. Meech PR, Hard! IRT, Hasrley LC, et al.: Gastrointestinal complications following renal transplantation. Aust NZ J Surg 49:61 2-625, 1979. 13. Meyers WC, Harris N, Stein S, et al.: Alimentary tract complications after renal transplantation. Ann Surg 190:535-542, 1979. 14. Owens ML, Passaro E, Wilson SE, et al.: Gastrointestinal complications after renal transplantation. Predictive factors and morbidity. Arch Surg 111:467-471, 1976. 15. Peterson R: Gastrointestinal abnormalities in renal homotransplant patients. J Can Assoc Radiol 27:240-249, 1976. 16. Rosekrans P: Gastrointestinal complications after renal transplantation. Radiologia Clin 47:32-43, 1978. 17. VanDerVliet J A , Koofstra G, Scholten AP, et al.: Gastric carcinoma in a renal allograft recipient. Neth J Med 23:252-255, 1980. 18. Faro RS, Corry RJ.: Management of surgical gastrointestinal complications in renal transplant recipients. Arch Surg 114:310-312, 1979. 19. Hadjiyannakis EJ, Evans DB, Smellie WA, et al.: Gastrointestinal complications after renal transplantation. Lancet 2:781-785, 1971. 20. Schnyder PA, Basch RC, Salvatierra O: Gastrointestinal complications of renal transplantation in children. Radiology 130:361-366,1979. 21. Oddson TA, Johnrude IS, Jackson DC, et al.: The diagnostic evaluation of patients with acute gastrointestinal hemorrhage with special attention to the changing role of barium examinations. Radiol Clin North Am 1 6:1 23-1 34, 1 978. 22. Canavan JS, Briggs JD, Bell PR: Gastric acid secretion following renal transplantation. Br J Surg 62:737-740, 1975. 23. Thompson WM, Myers W, Seigler HE, etal.: Gastrointestinal complications of renal transplantation. Semin Roentgenol 13:319-328,1978. 24. Dickermann RM, Niederhuber JE, Eigenbrodt E, et al.: Portal hypertension following renal transplantation. Surgery 84:322-328, 1978. 25. Lauffer I: Inflammatory disorders of the esophagus, pp. 90-128 in: Double Contrast Gastrointestinal Radiology. WB Saunders, Philadelphia, 1979. 26. Lewicki AM, Moore JP: Esophageal moniliasis: A review of common and less frequent characteristics. Am J Roentgenol 125:218-225, 1975. 27. Archibald SD, Jirsch DW, Bear RA: Gastrointestinal complications of renal transplantation: 1: The upper gastrointestinal tract. Can Med Assoc J 11:1291-1296,1978. 28. Berg B, Groth CG, Magnusson G, et al.: Gastrointestinal complications in 24 kidney transplant patients. Scand J Urol Nephrol 29 Suppl. 19-20,1975. 29. Blohme I: Gastro-duodenal bleeding after renal transplantation. Scand J Urol 29 Suppl. 21-23, 1975. 30. Chisholm GD, Mee AD, Williams G, et al.: Peptic ulceration, gastric secretion and renal transplantation. Br Med J 1:163-1633,1977. 31. Diethelm AG: Surgical management of complications of steroid therapy. Ann Surg 184:251-263, 1977.


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32. Foucar E, Mukai K, Sutherland DE: Major colonic hemorrhage due to cytomegalovirus infection. Minn Med 64:211-214, 1981. 33. Frahzin G, Novell! P, Fratton A: Histologic evidence of cytomegalovirus in the duodenal and gastric mucosa of patients with renal allograft. Endoscopy 12:117-120, 1980. 34. Owens ML, Passaro E, Wilson SE, et al.: Treatment of peptic ulcer disease in the renal transplant patient. Ann Surg 186:1 7-21, 1977. 35. Penn I, Groth CG, Breetschneider L, et al.: Surgically correctable intraabdominal complications before and after renal homo-transplantation. Ann Surg 168:865-870, 1968. 36. Prompt CA, Lee DB, Upham AT, etal.: Medical complications of renal transplantation. Part II: Noninfectious complications in recipients. Urology 9:32-48, 1977. 37. Conn HO, Blitzer L: Nonassociation of adrenocortico steroid therapy and peptic ulcer. N Engl J Med 294:473-479, 1976. 38. Cho SR, Jaime T, Chung L, et al.: Bleeding cytomegalovirus ulcers of the Colon: Barium enema and angiography. A J R 136:1213-1215, 1981. 39. Castaneda-Zuniga WR, Jauregui H, Amplatz K, et al.: Bleeding from cecal ulcer in renal transplant patients. Rev Interam Radiol 3:27-31, 1978. 40. Evans DJ: Cytomegalic inclusion disease in the adult. J Clin Path 21:311-316,1968. 41. Doherty CC, McGoewn MG: Peptic ulceration, gastric secretion and renal transplantation. Br Med J 2:188, 1977. 42. Sodal G, Jakobson A, Flatmark A: Effect of prophylactic gastric resection on upper gastrointestinal complications in uremic and transplanted patients. Scand J Urol Nephrol 29:29-31, 1975. 43. Spanos PK, Simmons RL, Rattazzi LC, et al.: Peptic ulcer disease in the transplant recipient. Arch Surg 109:193-197, 1974. 44. Jones RH, Rudge CJ, Bewick M, et al.: Cimetidine: Prophylaxis against upper gastrointestinal hemorrhage after renal transplantation. Br Med J 1:398-400, 1 978. 45. Kaskikova j, Kocandrle V, Zastava V, et al.: Multiple immunoblastic sarcoma of the small bowel following renal transplantation. Transplantation 31:481 -482, 1 981. 46. Schiessel R, Starlinger M, Wolf A, et al.: Failure of cimetidine to prevent gastroduodenal ulceration and bleeding after renal transplantation. Surgery 90:456-458, 1981. 47. Stuart FP, Reckard CR, Shulak JA, et al.: Gastroduodenal complications in kidney transplant recipients. Am J Surg 194:339-366, 1981. 48. Arvanitakis C, Malek G, Uehling D, et al.: Colonic complications after renal transplantation. Gastroenterology 64:533-538, 1973. 49. Carlton PK, Whelchel JD: Massive colonic diverticular hemorrhage in a transplant patient. Am J Surg 44:159-161, 1978. 50. Zisbrod Z, Haimov M, Schauzer H, et al.: Kaposi's sarcoma after kidney transplantation. Transplantation 30:383-384, 1 980. 51. Aguilo J J, Zincke H, Woods JE, et al.: Intestinal perforation due to fecal impaction after renal transplantation. J Urol 11 6:153-1 55, 1 976. 52. Brettschneider L, Monafo W, Osborne DP: Intestinal obstruction due to antacid gels: Complication of medical therapy for gastrointestinal bleeding. Gastroenterology 49:291-294, 1965. 53. Lipschulz DE, Easterling RE: Spontaneous perforation of the colon and chronic renal failure. Arch Intern Med 132:758-759, 1973. 54. Gulp WC: Relief of severe fecal impactions with water soluble contrast enemas. Radiology 115:9-12,1975. 55. Matas AJ, Simmons RL, Kjellstrand CM, et al.: Increased incidence of malignancy during chronic renal failure. Lancet 1:883-886, 1975. 56. Perloff LJ, Chou H, Petrella EJ, et al.: Acute colitis in the renal allograft recipient. Ann Surg 183:77-83, 1976.

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57. Kyriakides GK, Simmons RL, Buls J, et al.: Paratransplant hernia: Three patients with a new variant of internal hernia. Am J Surg 1 36:629-630, 1 978. 58. Aaron KE, Dailey TH: Survival after colonic perforation of a patient with a transplant kidney. Report of a case. Dis Colon Rectum 17:103-105, 1974. 59. Bartolomeo RS, Calabrese PR, Tambin HL: Spontaneous perforation of the colon: A potential complication of chronic renal failure. Am J Dig Dis 22:656-657, 1 977. 60. Bernstein WC, Nivatvongs S, Tallent MD: Colonic and rectal complications of kidney transplantation in man. Dis Colon Rectum 1 6:255-263, 1973. 61. Demling RH, Salvatierra O, Jr., Belzer FO: Intestinal necrosis and perforation after renal transplantation. Arch Surg 110:251 -253, 1975. 62. Guice K, Rattazzi LC, Marchioro TL: Colon perforation in renal transplant patients. Am J Surg 138:43-48, 1979. 63. Hognestad J, Flatmark A: Colon perforation in renal transplant patients. Scand J Gastroenterol 11:289-292, 1976. 64. Sawyer Ol, Garvin PJ, Cod JE, et al.: Colorectal complications of renal allograft transplantation. Arch Surg 113:84-86, 1978. 65. Archibald SD, Jirsch DW, Bear RA: Gastrointestinal complications of renal transplantation 2: The colon. Can Med Assoc J 119:1301-1305, 1978. 66. Thompson WM, Seigler HF, Rice RP: lleocolonic perforation: A complication following renal transplantation. Am J Roentgenol 125:723-730, 1975. 67. Canter JW, Shorb PE: Acute perforation of colonic diverticula associated with prolonged adrenocorticosteroid therapy. Am J Surg 121:46-51, 1971. 68. Penn I: Development of cancer in transplantation patients. Adv Surg 12:155-191, 1978. 69. Renshaw TS, Phelps DB: Perforation of colonic diverticula: A life-threatening postoperative complication in patients receiving long-term corticosteroid therapy. J Bone Joint Surg 54:1070-1072, 1972. 70. Misra MK, Pinkus GS, Birtch AG, Wilson R: Major colonic diseases complicating renal transplantation. Surgery 73:942-948, 1973. 71. Penn I, Brettschneider L, Simpson K, et al.: Major colonic problems in human homotransplant recipient. Arch Surg 100:61-65, 1970. 72. Ahonen H, Eklund B, Lindfors O, et al.: Peptic ulceration in kidney transplantation. Proc Eur Dial Transplant Assoc 14:396-400, 1977. 73. Powis SJA, Barnes AD, Dawson-Edwards PD, et al.: lleocolonic problems after cadaveric renal transplantation. Br Med J 1:99-101, 1 972. 74. Miller RE, Nelson SW: The roentgenologic demonstration of tiny amounts of free intraperitoneal gas. Am j Roentgenol 112:579-585,1971. 75. Doherty CC, O'Connor FA, Buchanan KD, et al.: Treatment of peptic ulcer in renal failure. Proc Eur Dial Transplant Assoc 14:386-395,1977. 76. Margolis DM, Etheredgs EE, Garza-Garza R, etal.: Ischemic bowel disease following bilateral nephrectomy or renal transplant. Surgery 82:667-673, 1977. 77. Matas AJ, Mauer SW, Sutherland DE, et al.: Polar infarct of a kidney transplant simulating appendicitis. Am J Surg 131:383-385,1976. 78. Joshi SN, Gavin PJ, Sunwoo YC: Candidiasis of the duodenum and jejunum. Gastroenterology 80:829-833, 1981. 79. Johnson WC, Nabseth DC: Pancreatitis in renal transplantation. Am J Surg 171:309314,1970. 80. Renning JA, Warden CD, Stevens LE, et al.: Pancreatitis after renal transplantation. Am J Surg 123:293-296, 1972. 81. Woods JE, Anderson CF, Frohnet PP, et al.: Pancreatitis in renal allografted patients. MayoClin Proc 47:193-195, 1972. 82. Stephens DH, Sheedy PF: Computed tomography of the pancreas, pp. 251-274 in: Margulis AR, Burheune JF (eds): Alimentary Tract Radiology, Vol II. CV Mosby, St. Louis, 1979.


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83. Vansonnenberg E, Ferrucci J, Mueller PR, et al.: Drainage of abscesses and fluid collections: Technique results and application. Radiology 142:1-10, 1982. 84. Peitzman S, Agarwal BN: Hemorrhagic pancreatitis with duodenopancreatic fistula in a renal homograft patient. Am J Gastroenterol 63:420-422,1 975. 85. Hoover R, Fraumeni JF: Risk of cancer in renal transplant patients. Lancet 2:5557,1973. 86. Matas AJ, Simmons RL, Najarian JS: Chronic antigenic stimulation herpes, viral influx and cancer in transplant recipients. Lancet 1277-1 279, 1 975. 87. Mendelsohn G: Multiple tumors in a renal transplant recipient. Johns Hopkins Med J 139:253-256,1967. 88. Hara H, Yamane T, Yamashita K: Extramedullary plasmacytomas of the gastrointestinal tract in a renal transplant recipient. Acta Pathol J pn 29:661 -668, 1979. 89. Coggon DN, Rose DH, Ansell ID: A large bowel lymphoma complicating renal transplantation. Br J Radiol 54:417-420, 1981. 90. Jamieson NV, Thiru S, Calne RY, et al.: Gastric lymphomas arising in two patients with renal allografts. Transplantation 31:224-225, 1981. 91. Thiru S, Calne RY, Nagington J: Lymphoma in renal allograft patients treated with cyclosporin-A as one of the immunosuppressive agents. Transplant Proc 13:359364,1981. 92. Cerilli J, Rynasiewicz JJ, Lemos LB, et al.: Hodgkin's disease in human renal transplantation. Am J Surg 133:182-184, 1977.

CHAPTER 5

Radiology of Skeletal and Soft Tissue Changes H. Charles Walker, Jr., Carol C. Coleman, and David W. Hunter

The musculoskeletal changes seen after renal transplantation are a combination of the substrate of the renal osteodystrophy and changes produced by hemodialysis —problems that existed prior to the transplantation —plus a host of new problems that may be associated with immunosuppressive therapy. Osseous change may be evident on plain roentgenographic films in as many as 44% of the transplant recipients. 1 One in six patients receiving renal transplants may have orthopedic problems. 2 Skeletal damage, which represents a serious problem, is sometimes the only obstacle to rehabilitation of renal allograft recipients.

RENAL OSTEODYSTROPHY In 1883, Lucas3 first called attention to the association of renal and skeletal disease. In 1943, Liu and Chu4 introduced the term

Skeletal and Soft Tissue Changes

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"renal osteodystrophy" as an inclusive term for all types of bone disease known to be associated with chronic renal failure. Skeletal changes rarely become apparent sooner than 2 years after renal insufficiency becomes manifest.5 However, with the widespread availability of hemodialysis, longer survival time of uremic patients, and variable periods of chronic renal failure before transplantation, renal osteodystrophy is being seen more frequently. The most profound changes are usually in those patients who develop chronic renal failure early in life. Bone changes also depend on the severity of the renal disease and its duration. Prolonged hemodialysis often results in a more severely symptomatic renal osteodystrophy. Definitions The principal pathologic processes of renal osteodystrophy are secondary hyperparathyroidism and osteomalacia (or renal rickets). The bone disease of hyperparathyroidism is termed osteitisfibrosa; histologically, secondary hyperparathyroidism is present early in virtually all of the patients with chronic renal failure.6 Histologic examination reveals increased numbers of osteoclasts, increased bone resorption, and evidence of fibrous tissue in the bone and marrow. Osteomalacia, or renal rickets, is then superimposed to a variable degree on the changes of secondary hyperparathyroidism. The essential feature of osteomalacia is a change in the bone quality due to a reduction in the ratio of mineral to organic material. Pathologic changes result from inadequate or delayed mineralization of osteoid. Osteosclerosis is occasionally seen in renal osteodystrophy when there is an excessive amount of mineralized bone. It may be superimposed on osteitis fibrosa or osteomalacia. Osteoporosis frequently appears after dialysis is started; it is a prominent feature in renal transplant patients who are on longterm steroid therapy. Osteoporosis may be defined as a reduction in the amount of bone without any change in the chemical composition. 7 In renal osteodystrophy, some prefer the term osteopenia because the quantity of bone is diminished but its quality is also altered. 8

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Pathophysiology Parathyroid hormone is the principal regulator of calcium homeostasis in humans. In conjunction with vitamin D and the normal physiochemical equilibrium between the calcium in bone and the extracellular fluid, parathyroid hormone maintains the serum calcium at a relatively constant concentration. 9 The kidney also plays a major role in calcium homeostasis by excreting calcium and inorganic phosphate, activating vitamin D, and degrading parathyroid hormone.10 In the intestines, 1,25-dihydroxy vitamin D 3 acts to increase the absorption of calcium and phosphorus. In chronic renal failure,secondary hyperparathyroidism develops when the glomerular filtration rate falls below 15 ml/mn.11 The stimulation of the parathyroid gland, and resulting parathyroid hyperplasia, is thought to result from the inability of the diseased kidney to excrete phosphates.12 Phosphate retention leads to a reciprocal fall in the level of ionized calcium in the serum that in turn increases amounts of the parathyroid hormone, resulting in osteitis fibrosa. The pathophysiologic factors in the development of osteomalacia are not as clear. The severely diseased kidney, with insufficient renal parenchyma, has an impaired ability to convert 25hydroxy vitamin D 3 to the more active 1,25-dihydroxy vitamin D3. The hydroxylation of 1,25-dihydroxy vitamin D 3 occurs exclusively in the kidney, which gives it a central role in the metabolism of vitamin D.13 The lower levels of active vitamin D decrease the absorption of calcium across the intestinal barrier. The active form of vitamin D has potent and rapidly acting antirachitic properties. Increased growth, and healing of bone lesions, have been reported in childhood renal osteodystrophy treated with 1,25-dihydroxy vitamin D 3 or 1-alpha-hydroxy vitamin D3.14>15 On the other hand, some believe that the serum calcium concentration is more important than the serum concentration of vitamin D metabolites for bone remodeling in chronic renal failure.16 Insignificant correlation is present between the vitamin D metabolites and the histomorphometric values in patients with chronic renal failure. It is controversial whether 1,25-dihydroxy vitamin D 3 has a direct feedback effect on parathyroid hormone secretion. We do not know why osteosclerosis is a prominent feature in some cases of renal osteodystrophy. It is present in some cases of primary hyperparathyroidism17 but is found more commonly in


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secondary hyperparathyroidism associated with renal failure. It may be a consequence of increased parathyroid hormone secretion. The hormone has been shown to induce osteosclerosis in intact animals by increasing the rate of bone formation to a level greater than the rate of bone resorption.18 Conversely, thyrocalcitonin inhibits resorption and thus effects a net increase in bone, acting independently of parathyroid hormone.19 Radiologic Findings and Other Methods of Measurement Iliac crest bone biopsy is sometimes used to determine histologically the predominant disease process. In chronic renal failure, however, several pathophysiologic processes are acting in concert to produce the skeletal changes seen in renal osteodystrophy. 9 Hyperparathyroidism induces increased bone turnover, and the resultant excess osteoid may calcify under certain conditions to produce osteosclerosis. Osteomalacia, by lowering the serum calcium, may accentuate the hyperparathyroidism. A decreased amount of mineralized bone may be either the result of the resorptive changes of osteitis fibrosa or a manifestation of nonspecific osteoporosis. Iliac crest biopsy is an invasive procedure that only samples a small area of bone. Radiologic methods, including microradiography and magnification radiography, are often used to follow serially the bone changes of renal osteodystrophy.10'20'21'22 Hyperparathyroidism Subperiosteal bone resorption is virtually pathognomonic of hyperparathyroidism. It is seen earliest and most frequently in the termiphalangeal tufts23 and along the radial aspect of the proximal and middle phalanges, particularly of the second and third fingers (fig. 5.1). Subperiosteal bone resorption may also be detected on the proximal medial aspects of the humerus, tibia, and femur; on the ribs; and in the lamina dura of the teeth. When seen at these other sites, it is almost invariably also present in the hand.24 Hand roentgenograms are thus the method most frequently used to search for evidence of secondary hyperparathyroidism. The involvement is symmetrical; intracortical bone resorption, endosteal bone resorption, subchondral bone resorption, and trabecular bone resorption may be present. These radiologic findings are not specific, but they are occasionally noted in secondary hyperparathyroidism.

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Walker, Coleman, and Hunter

Figure 5.1. Subperiosteal resorption and soft tissue calcification. The loss of definition in the tufts of the third and fourth digits and "lacy" appearance of the cortex on the radial aspect of the phalanges are pathognomonic of hyperparathyroid-

ism. Periarticular soft tissue calcifications are present at the second metacarpal phalangeal joints and the third distal interphalangeal joint. Nodular calcification replaces the tufts of the second digit. Also observe the vascular calcification.


69

Brown tumors are more characteristic of primary hyperparathyroidism where they may become quite large. Osteolysis occasionally may be seen at sites of tendon and ligament attachments to bone. The characteristic "salt and pepper" skull (fig. 5.2) due to trabecular bone resorption appears in moderately advanced hyperpa rathyroidism.8

Figure 5,2. "Salt and pepper" skull indicates trabecular bones resorption in this

patient with moderately advanced secondary hyperparathyroidism.

Osteosclerosis is a prominent feature in some cases of renal osteodystrophy. It may be localized or diffuse, with or without roentgenographic signs of hyperparathyroidism.25 It is most commonly observed in the metaphyseal ends of the long bones, pelvis, skull, and spine. The vertebrae commonly show a diffuse osteosclerosis. The central portion of the vertebra may be more radio-

70


lucent, with osteosclerosis visible superiorly and inferiorly to produce the "rugger-jersey spine" (fig. 5.3). Meema et al.26 suggested the term periostea/ neostosis to distinguish the heterotrophic type of periostea! new bone formation, which is present rarely in renal osteodystrophy (fig. 5.4). They believe that the pathogenesis is osteitis fibrosa, with fibrous tissue proliferating beyond the confines of the original cortex, thus displacing and elevating the periosteum. Osteomalacia and Renal Rickets Osteomalacia, which develops subsequent to secondary hyperparathyroidism,6 is best defined histologically. "Looser's zones" or "Milkman's pseudofractures" (fig. 5.5), which are a characteristic of Osteomalacia, are rare roentgenographic findings in adult renal osteodystrophy. These pseudofractures, which represent focal accumulations of osteoid, tend to be symmetric and to occur at right angles to the cortex. They have a predilection for the inner margins of the proximal femora and for the superior and inferior pubic rami. Osteomalacia contributes to the osteopenia and "coarsened trabecular pattern" that are common in renal osteodystrophy but are nonspecific. The coarsened trabecular pattern is seen best in spongy bone: A decreased number of trabeculae cause the remaining trabeculae to appear prominent. In children, gross rachitic changes (fig. 5.6) are often evident, but some of these changes are probably related to the coexisting secondary hyperparathyroidism. 27 The more rapidly the skeleton grows, the more severe the skeletal change will be in the child. Bone deformities may result (fig. 5.5). Early radiologic changes include widening of the epiphyseal plate, with poor definition or fraying of the metaphyses (fig. 5.6A and B). As the disease progresses there is widening and cupping of the metaphyses and epiphyseal irregularities (fig. 5.7). These patients are prone to epiphyseal slippage or fracture (figs. 5.6C and 5.8A). Slipped epiphyses occur much more frequently in nondialyzed children in chronic renal failure than in those who are dialyzed.28 These may eventually require orthopedic procedures to correct deformities. Growth retardation, or in some cases dwarfism (fig. 5.9), is a prominent feature.


Figure 5.3. "Rugger-jersey" spine, with osteosclerosis adjacent to the end plates. Analgesics used for this patient's obvious ankylosing spondylitis were probably re-

77

sponsible for the chronic renal failure. Note the loosening of the total hip arthroplastly, as manifested by a wide lucent line at the bone-cement surface.

72


Figure 5.4. Periostea! neostosis, proximal femur. This periosteal new bone formation in renal osteodystrophy is believed

to be related to osteitis fibrosa. (Courtesy Dr. Richard McLeod, Mayo Clinic.)


Figure 5.5. Looser's zones. Iliac crest biopsy demonstrated osteomalacia and focal osteitis fibrosa. This patient also had moderate osteosclerosis (A) Pseudofractures (arrows) in the proximal femora

73

are relatively symmetric. (B) In the lateral projection of the right hip, the pseudofracture extends across the neck of the femur.

14


Figure 5.6. Renal osteodystrophy. (A) Marked genu valgus with early rachitic changes in the knees. This 12-year-old

patient received a renal allograft 7 years later.


5.6. (B) More advanced rachitic changes and secondary hyperparathyroidism are

75

present in the hand and wrist 2 years later.

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5.6. (C) Advanced rachitic changes are also evident in the hip, with a slipped left femoral epiphysis. There is bilateral

coxa vara. A brown tumor is present in right proximal femur. The left hip was stabilized by pinning.


Figure 5.7. Advanced rachitic changes in renal osteodystrophy. Observe the widening of the epiphyseal plate and the

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widening, cupping, and fraying of the distal femoral metaphysis.

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Walker, Cafeman, and Hunter

Figure 5,8. (A) Rachitic changes, including slipped radial and ultiar epiphyses. Observe the frayed, irregular distal ulnar

and the dense osteosclerosis in radial and ulnar metaphyses in this 7*year-otd child just before transplantation.


5.8, (B) Three years after renal allograft, no rachitic'changes are present in the knee; however, some metaphyseal sclero-

79

sis persists and a "coarsened trabecular pattern" is evident.

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Walker, Co lemon, and Hunter

Figure 5.9. Renal dwarfisrn and calcified aorta at age 17 {bone age of 9). Chronic renal failure was diagnosed at age 4, and she received the first of three separate renal allografts at age 10, Observe the unf used sacra! segments and the coarsened trabecuiae in the osteopenic spine.

Osteoporosis

The radiologic diagnosis of osteoporosis, or osteopenia, is frequently made on the basis of a subjective evaluation of increased radioiucency of bone and thinning of the cortices. This diagnosis is obviously not specific: many conditions may lead to radiolucent bone. The reported incidence of osteopenia in renal ostedystrophy varies greatly, with some investigators considering osteoporosis in the nondialysed patient to be unusual. Attempts to quantitate bone rarefaction by X-ray densitometry or cortical thickness measurements have likewise produced inconsistent results. The spine is commonly examined roentgenologically to evaluate for generalized osteoporosis (fig. 5.10). In this procedure, one Figure 5,W, Osteopenia and vertebral compression. There is flattening of T12L2 vertebra and biconcave compression

of L3-L5 vertebra. This 26-year-oid man had his first renai ailograft at age 14,


87

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not only considers rarefaction but also the trabecular pattern and the vertebral shape. Compression fractures frequently occur in the vertebrae. A coarsened trabecular pattern is very common in both chronic renal failure and transplant patients, resulting from the osteoporosis as well as coexisting osteomalacia and other factors that contribute to osteopenia. In a blind evaluation of the spine in nondialysis patients with renal osteodystrophy, Andresen and Nielsen found rarefaction in 45% of the patients.29 This figure is higher than in most series, but they had a mean observation time of 3.5 years. Soft Tissue Calcification Metastatic calcification occurs in previously normal tissues exposed to an abnormal environment. Dystrophic calcification occurs in abnormal, usually necrotic, tissue. In chronic renal failure, both factors are believed to be active.30 Arterial calcification, almost invariably of the Monckeberg type, is commonly present in patients who have renal osteodystrophy. It is most often recognized roentgenologically in peripheral arteries (fig 5.1), but large vessels may be involved (fig. 5.8). Diabetic transplant recipients are more prone to occlusive vascular disease, often with associated gangrene and osteomyelitis. Particularly after long-term hemodialysis, soft tissue calcification may be noted in periarticular tissues in either a nodular (fig. 5.1) or tumoral form (fig. 5.11). Calcification may rarely appear in the joint capsule or in the hyaline or fibrocartilage of the joints. Cutaneous and subcutaneous calcifications may be seen. Visceral calcification occurs in the lungs, kidneys, stomach, and heart, but these deposits are rarely detectable during life.30 It is generally believed that soft tissue calcifications are related to an increased calcium-phosphorus ion product and systemic pH changes.30 To some extent, soft tissue calcifications can be prevented. Persistent hypercalcemia, or a calcium-phosphate product greater than 70,are indications for urgent reassessment of therapy.9 The deposition of calcium salts is a complex process, however, in which a high calcium-phosphate product is only one of many factors involved.31 The arterial calcification and the nonvisceral soft tissue calcification are hydroxyapatite.32 The visceral calcification is a microcrystalline compound composed of calcium, magnesium, and phosphorus in a constant molar ratio, somewhat like whitlockite.


Figure 5 . 7 7 . Metastatic calcification approaching tumorlike proportion in this

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patient with chronic renal failure. (Courtesy Dr. Richard McLeod, Mayo Clinic.)

SKELETAL AND SOFT TISSUE CHANGES AFTER RENAL ALLOGRAFT Renal Osteodystrophy after Renal Transplantation Because renal transplantation restores near normal renal physiology, it could theoretically result in a complete cure of renal osteodystrophy. The transplanted kidney would be expected to normalize vitamin D metabolism, calcium-phosphate balance, and parathyroid function. In some patients, there is a regression of osteitis fibrosa and osteomalacia.33 Most reports indicate, however, that there is no improvement in the osteopenia. Histomorphologic studies show that bone volume continues to decrease for at least 96 months after transplantation, with the critical period being the first

84


year.34 Photon absorptiometry of bone during the first 6 months after successful renal transplantation demonstrated significant loss of mineral in 57% of the recipients; at 18 months, the mean bone mineral index was still significantly lower than controls. 35 Hyperparathyroidism frequently persists in both short-term and long-term transplant patients,34 presumably because of the persistent parathyroid hyperplasia with nonsuppressible baseline secretion of parathyroid hormone. Occasionally there is a reinforcement of this autonomous or tertiary hyperparathyroidism, aggravating bone loss postoperatively and necessitating parathyroidectomy. An effect of the allograft on vitamin D metabolism is suspected of being responsible for the accentuated bone loss.36 Osteosclerosis, when present, may regress after transplantation (fig. 5.8B), but in most patients who have this manifestation there is a progressive increase in bone density. 1

Figure 5.12. Exaggerated stress lines of Park. The transverse bands in the metaphyses about the knee were also present in the proximal humeri. They represent

a resurgence of growth activity after a period of growth arrest. Observe the severe osteopenia that serves to accentuate these bands.


85

There may be some healing of the osteomalacia after renal allograft,37 but some evidence may persist. Histomorphologic studies show that the mean osteoid index was elevated to the same degree in both short- and long-term transplant patients, but the mean osteoid index was not nearly as high as in long-term dialyzed uremics.34 Rachitic changes in children are usually rapidly reversed, despite immunosuppression. 38 Successful renal transplantation may normalize the bone maturation rate in children with chronic renal failure.15 Occasionally, a massive growth spurt will occur in the first year following transplantation, as evidenced by exaggerated transverse lines in the metaphyses of long bones (fig. 5.12) or marginal lines in the flat bones.39 However, most children grow slightly slower than normal.38 At the University of Minnesota, diabetic patients are 15-20% of all transplant recipients. In general, they do worse than nondiabetic transplant patients.40 Diabetic-uremic neuropathy often improves, but some of these patients still have neuropathic joint disease after transplantation (fig. 5.13). Madsen et al. studied 11 necrograft recipients 6 years after transplantation when prednisone had been withdrawn for 1.5 years.41 They concluded that some regression of the renal osteodystrophy may take place after successful transplantation but that decreased mineralization of the appendicular skeleton persists. It was uncertain whether the persistent osteopenia represented an irreversible component of renal osteodystrophy or whether it resulted from prior steroid therapy. Complications Related to Immunosuppressive Agents and Adrenal Steroids The immunosuppressive agents and adrenal steroids that are necessary during the posttransplant period have been implicated in several skeletal complications. The use of steroids after renal transplantation perpetuates the suppression of bone formation and contributes to osteopenia.34'41 The most common skeletal complications after renal allograft are osteonecrosis, spontaneous fractures, osteomyelitis, and septic arthritis.

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Walker, Cofeenan, and Hunter

Figure 5.13. (A) Early neuropathic joint disease, right ankle. This 27-year-old man had juvenile onset diabetes mellitos and diabetic triopathy; his renal transplant was performed 6 months previously. Observe the healing spontaneous fracture of the lateral malieoius. There is osteoscierosis and some collapse of the talus, and multiple joint bodies are evi-

dent. The ieft ankle was normal at this time, (S) Advanced neutopathic joint disease, right ankle, and moderate neuropathic changes, ieft hind foot, 33 months later, Observe the marked disintegration of the right ankle and hind foot. The ieft talus and calcaneus show evidence of fracture, collapse, and fragmentation.


87

Osteonecros/s Osteonecrosis is an important complication of renal transplantation, often necessitating a surgical approach to treatment. No means of prophylaxis is known. The reported incidence of osteonecrosis in renal transplant recipients averages 22% in recent published reports with a composite of 1,076 patients.1-36'42'46 The incidence of osteonecrosis in children is about the same as in adults.47 Usually, the clinical symptoms of osteonecrosis are present a few months before the radiologic changes are manifest. The interval between the transplant operation and the onset of osteonecrosis ranges from 1 month to 4 years, with more than half occurring in the first year.36 The bone lesions are primarily localized to weight-bearing cancellous bone, most often in the femoral heads (figs. 5.14 and 5.15). Involvement is frequently bilateral. Other locations of involvement are, in order of decreasing frequency, the femoral condyles (fig. 5.16), ankle bones (fig. 5.1 7), humeral head (fig. 5.1 8), and rarely the carpal (fig. 5.19) or midtarsal bones. The early radiologic signs of osteonecrosis are the "crescent sign" (figs. 5.14A and 5.18A), loss of continuity of thesubchondral bone or a cortical step-off (fig. 5.15), and subtle alterations in the density of the cancellous bone (fig. 5.14A). 48 Rarely, the osteonecrosis may become arrested or regress; but there is usually progressive collapse of the articular cortex with eventual flattening, especially in weight-bearing joints (fig. 5.15). Disintegration of the underlying bone and secondary osteoarthritis with loose joint bodies in some may be the end result (fig. 5.14B). The radiologic changes in the hip of osteonecrosis are often best demonstrated with a frogleg position and with a knee in the lateral projection. In the knee and at times in the ankle, osteonecrosis may initially resemble osteochondritis dissecans—a different roentgenographic manifestation of osteonecrosis, but probably the same pathologic process. Cases resembling osteochondritis dissecans (figs. 5.16 and 5.20) may be minimally symptomatic and may regress, or they may progress to collapse. Osteonecrosis of the femoral condyle may simulate osteochondral fractures (fig. 5.21 A). In the shoulder, the only manifestations of osteonecrosis may be variation in bone density (fig. 5.21B). The intramedullary bone infarcts that may also be seen have a predilection for the metadiaphyseal region of the proximal and distal femur and the proximal humerus. The pathologic findings of osteonecrosis have been well described.43'49'50 A combined autoradiographic and histologic study

88


Figure 5.14, (A) Early osteoirecrosis, hip. The subehondral bone fragment appears detached medially, and a crescent-

shaped radio! ucency is present subchon81~85 hematuria may be present. Graft rupture is almost always preceded by overt rejection signs.80 As can be expected, graft rupture is most commonly encountered after cadaver transplant.85 In some reports, renal biopsy was believed to be the major factor leading to rupture of the graft.82'84'86'87

TUMORS About 6% of renal transplant recipients are affected by de novo malignancies.88 Most lesions are squamous cell carcinomas of the skin and lips.88'89 As kidney transplants are performed more in an older age group and as the overall survival of transplant patients increases, lymphomas are seen more often (fig. 6.13). To date, about 20% of posttransplant malignancies are lymphomas.90"92 The posttransplant lymphoma differs from other lymphomas by morphologic appearance and clinical course.90'92 The increased incidence of malignant tumors in immunosuppressed patients is well known; it can be demonstrated in practically every organ.93 Tumors in the transplanted kidney have mostly been carcinomas or sarcomas, more seldom metastases or primary tumors that have been overlooked before transplantation.94"100 The role of excretory urography is limited in this patient population. The consequences of tumor demonstration are obvious, however, and in elective cases this radiographic technique may supplement ultrasonography and angiography. The treatment includes radical transplantectomy and modification of the immunosuppressive therapy.14'93

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Salomonowitz and Goldberg

Figure 6.73. Transplant kidney with lymphoma developing 10 years after transplantation. (A) Urge mass is seen

displacing the upper pole of the transplanted kidney.

Urologic Complications

6.13. (B) Note the relative lucency visible in the center of the mass.

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6.13. (C) Computed tomography of kidney shows the tumor with homogeneous

low dense center infiltrating psoas margin (left] and kidney (right}.

VASCULAR PROBLEMS Vascular complications occur at a lower rate in the early postoperative period when compared with urologic complications. Excretory urography plays no major role in diagnosis and management of these cases. However, in cases of kidney enlargement of unknown cause with concomitant clinical symptoms of decreased transplant function, the radiologist should be alerted to the possibility of vascular complications before angiography is performed because the transplanted kidney may not tolerate a large burden of contrast medium. Vascular complications after transplantation have been reported in from 6.5%15 to as many as 30% of the renal transplant recipients. Arterial stenosis or occlusion (12%) was the most common finding, and venous thrombosis (4%) was less common.22'24 Renal artery stenosis may be secondary to a rejection episode, extrinsic tumefaction, or infection.101"106 Renal vein thrombosis is usually the result of compression by an extrinsic mass, mostly a lymphoC e|e. 104,105,107 Renal arteriovenous fistula commonly occurs after percutaneous needle biopsy of the transplanted kidney. Excretory urography, of course, gives no diagnostic clue in these cases. This entity is included here for differential diagnostic considerations. Furthermore, the small fistulae are usually insignificant because they have a tendency to heal spontaneously.15'22'24'108'109


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REFERENCES 1. Burgener FA, Schabel SI: The radiographic size of renal transplants. Radiology 117: 547-550, 1975. 2. Imray TJ, Gedgaudas E: Excretory urography in the evaluation of renal transplants. Radiology 95:653-656, 1970. 3. Anderson CB: Metal marker fixation on transplanted kidneys. Urology 4:607, 1974. 4. Ansell G: Adverse reactions to contrast agents. Scope of problem. Invest Radiol 374-391,1970. 5. Meaney TF, Lalli AF, Alfidi RJ (Eds.): Complications and Legal Implications of Radiologic Special Procedures. St. Louis: CV Mosby, 1973. 6. Shedadi, WH: Adverse reactions to intravascularly administered contrast media; a comprehensive study based on a prospective survey. AJR 124:145-152, 1975. 7. Salvatierra O, Olcott C, Amend WJ, Cochrum KC, Feduska NJ: Urological complications of renal transplantation can be prevented or controlled. J Urol 117:421-424, 1977. 8. Leary FJ, Woods JE, DeWeerd JH: Urologic problems in renal transplantation. Arch Surg 110:1124-1126, 1975. 9. Starzl TE, Groth CG, Putnam CW, etal: Urological complications in 216 human recipients of renal transplants. Ann Surg 172:1-22,1970. 10. Murray JE, Hartwell-Harrison J: Surgical management of 50 patients with kidney transplants including 18 pairs of twins. Am J Surg 105:205-218,1963. 11. Martin DC, Mims MM, Kaufman JJ, Goodwin WE: The ureter in renal transplantation. J Urol 101:680-687, 1969. 12. Straffon RA, Riser WS, Stewart BH, Hewitt CB, Gifford RW, Nakamoto S: Four years clinical experience with 138 kidney transplants. J Urol 99:479-485, 1968. 13. Palmer JM, Chatterjee SN: Urologic complications in renal transplantation. Surg Clin North Am 58:305-319, 1978. 14. Waltzer WC, Woods JE, Zincke H, DeWeerd JH, Leary FJ, Myers RP, Sterioff S: Urinary tract reconstruction in renal transplantation. Urology 16:233-241, 1980. 15. Becker JA, Kutcher R: Urologic complications of renal transplantation. Semin Roentgenol 1 3:341 -351, 1 978. 16. Barry JM, Lawson RK, Strong D, Hodges CV: Urologic complications in 1973 kidney transplants. J Urol 112:567-571,1974. 17. Lynne CM, Carrion HM, Vanderwerf BA: Urological complications of renal transplantation. Urology 4:525-531, 1974. 18. Mundy AR, Podesta ML, Bewick M, Rudge CJ, Ellis FG: The urological complications of 1 000 renal transplants. Br J Urol 53:397-402, 1981. 19. Reitamo T, Laasonen L, Kock B, Edgren J: Urography and isotope renography following renal transplantation. Scand J Urol Nephrol 1 3:283-285, 1979. 20. Novick AC, Irish C, Steinmuller D, Buonocore E, Cohen C: The role of computerized tomography in renal transplant patients. J Urol 125:15-18, 1981. 21. Kaude J V, Stone M, Fuller TJ, Cade R, Tarrant DG, Juncos LT: Papillary necrosis in kidney transplant patients. Radiology 120:69-74, 1976. 22. Ehrlich RM, Smith RB: Surgical complications of renal transplantation. Urology 10: 43-56, 1977. 23. Gregory JG, Codd JE, Groce A, Graff R, Anderson CB, Newton WT: Aggressive management of genitourinary complications of renal transplantation. Urology 7:349354,1976. 24. Holden S, O'Brien DP, Lewis EL, Green BG, Walton KN: Urologic complications in renal transplantation. Urology 5:182-184,1975.

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25. Pfeffermann R, Vidne B, Leapman S, Butt K, Kountz S: Urologic complications in renal primary and retransplantation. Experience with 202 consecutive transplants. Am J Surg 1 31:242-245, 1 976. 26. Rosenbusch G, Debryune FMJ: Urological complications after kidney transplantation. Radiol Clin 47:13-21, 1978. 27. Smith RB, Ehrlich RM: The surgical complications of renal transplantation. Urol Clin North Am 3:621-646, 1976. 28. Smolev JK, McLoughlin MG, Rolley R, Sterioff S, Williams GM: The surgical approach to urological complications in renal allotransplant recipients. J Urol 117:1012, 1977. 29. Cook GT, Cant JD, Crassweller PO, Deveber GA: Urinary fistulas after renal transplantation. J Urol 118:20-21, 1977. 30. Malek GH, Uehling DT, Daouk AA, Kisken WA: Urological complications of renal transplantation. J Urol 109:173-176, 1973. 31. Marx WL, Halasz NA, Mclaughlin AP, Gittes RF: Urological complications of renal transplantation. J Urol 112:561-563, 1974. 32. Frodin L, Lodin H, Wibell L, Wicklund H: Aspects of the diagnosis of ureteric complications following renal transplantation. Scand J Urol Nephrol 29 (Suppl):1 07-110, 1975. 33. Libertino JA, Rote AR, Zinman L: Ureteral reconstruction in renal transplantation. Urology 12:641-644,1978. 34. Schiff M, McGuire EJ, Weiss RM, Lytton B: Management of urinary fistulas after renal transplantation. J Urol 115:251-256, 1976. 35. Vallely JF, Sharpe JR, Hayman WP, Stiller CR, Ulan RA: Spontaneous rupture of the renal pelvis: Complication of renal homotransplantation. J Urol 116:253-254, 1976. 36. Goldman MH, Burleson RL, Tilney NL, Vineyard GC, Wilson RE: Calycealcutaneous fistulae in renal transplant patients. Ann Surg 184:679-681, 1976. 37. Schiff M, McGuire EJ, Webster J: Successful management of caliceal fistulas following renal transplantation. Arch Surg 110:1129-1132, 1975. 38. Goldstein I, Cho SI, Olsson CA: Nephrostomy drainage for renal transplant complications. J Urol 126:159-163, 1981. 39. Lieberman RP, Crummy AB, Glass NR, Belzer FO: Fine needle antegrade pyelography in the renal transplant. J Urol 126:155-158, 1981. 40. Turner AG, Howlett KA, Eban R, Williams GB: The role of anterograde pyelography in the transplant kidney. J Urol 123:812-814, 1980. 41. Barry JM, Lawson RK, Strong B, Hodges CV: Urologic complications in 1973 kidney transplants. J Urol 112:567-571, 1974. 42. Hricko GM, Birtch AG, Bennett AH, Wilson RE: Factors responsible for urinary fistula in the renal transplant recipient. Ann Surg 1 78:609-615, 1973. 43. Simmons RL, Tallent MB, Kjellstrand CM, Najarian JS: Kidney transplantation from living donors with bilateral double renal arteries. Surgery 69:201 -207, 1971. 44. Spanos PK, Simmons RL, Kjellstrand CM, Buselmeier TJ, Najarian JS: Kidney transplantation from living related donors with multiple vessels. A problem revisited. Am J Surg 125:554-558, 1973. 45. Brockis JG, Golinger D, Haywood EF, House AK, Hurst P, Saker B, Van Merwyk A: The management of urinary fistulae following cadaveric renal transplantation. Br J Urol 47:371-375, 1975. 46. Simmons RL, Kjellstrand CM, Kyriakides GK, Rattazzi LC, Spanos PK, Casali R, Najarian JS: Surgical aspects of transplantation in diabetic patients. Kidney Int 1 (Suppl):129-I32,1974. 47. Spigos DG, Tan W, Pavel DG, Mozes M, Jonasson O, Capek V: Diagnosis of urine extravasation after renal transplantation. AJR 129:409-413, 1977.


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48. Texter JH, Haden H: Scintiphotography in early diagnosis of urine leakage following renal transplantation. J Urol 116:547-549, 1976. 49. Dunningham TH: Periureteric fibrosis complicating kidney transplantation. Urology 6:363-366,1975. 50. McLoughlin MG: Late ureteric obstruction in renal transplantation. Br J Urol 49:9396, 1977. 51. Schweizer RT, Bartus SA, Kahn CS: Fibrosis of a renal transplant ureter. J Urol 117:125-126,1977. 52. Zincke H, Woods JE, Mattery RR, Leary FJ, DeWeerd JH: Later ureteral obstruction mimicking rejection after renal transplantation. Urology 9:504-508, 1977. 53. Karmi SA, Dagher FJ, Ramos E, Young JD: Spermatic cord: Cause of ureteral obstruction in renal allotransplant recipients. Urology 11:380-383, 1978. 54. Fletcher EWL, Lecky JW: The radiological demonstration of urological complications in renal transplantation. Br J Radiol 42:886-891,1969. 55. Lamasters D, Katzberg RW, Confer DJ, Slaysman ML: Ureteropelvic fibrosis in renal transplants: Radiographic manifestations. AJ R 1 35:79-82,1 980. 56. Basinger GT, Gittes RF: Lymphocyst: Ultrasound diagnosis and urologic management. J Urol 114:740-745, 1975. 57. Bear RA, McCallum RW, Cant J, Goldstein MB, Johnson M: Perirenal lymphocyst formation in renal transplant recipients: Diagnosis and pathogenesis. Urology 7:581586,1976. 58. McLoughlin MG, Williams GM: Late perirenal lymphocele causing ureteral and arterial obstruction in renal transplant patients. J Urol 114:527-529, 1975. 59. Mott C, Schreiber MH: Lymphoceles following renal transplantation. A J R 1 22:821827,1974. 60. Lorimer WS, Glassford DM, Sarles HE, Remmers AR, Fish JC: Lymphocele: A significant complication following renal transplantation. Lymphology 8:20-23, 1975. 61. Koehler PR, Kyaw MM: Lymphatic complications following renal transplantation. Radiology 102:539-543, 1972. 62. Lerut T, Lerut J, Broos P, Gruwez JA, Michielsen P: Lymphatic complications in renal transplantation. Eur Urol 6:83-89, 1980. 63. Howard RJ, Simmons RL, Najarian JS: Prevention of lymphoceles following renal transplantation. Ann Surg 18:166-168, 1976. 64. Leapman SB, Vidne BA, Butt KM, Waterhouse K, Kountz SL: Nephrolithiasis and nephrocalcinosis after renal transplantation: A case report and review of the literature. J Urol 115:129-132,1976. 65. Lucas BS, Castro JE: Calculi in renal transplants. Br J Urol 50:302-306,1978. 66. Normann E, Fryjordet A, Halvorsen S: Stones in renal transplants. Scand J Urol Nephrol 14:73-76, 1980. 67. Rattiazzi LC, Simmons RL, Markland C, Casali R, Kjellstrand CM, Najarian JS: Calculi complicating renal transplantation into ileal conduits. Urology 5:29-31, 1975. 68. Rosenberg JC, Arnstein AR, Ing TS, Pierce JM, Rosenberg B, Silva Y, Walt AJ: Calculi complicating a renal transplant. Am J Surg 129:326-330,1975. 69. Schweizer RT, Bartus SA, Graydon RJ, Berlin BB: Pyelolithotomy of a renal transplant. J Urol 117:665-666, 1977. 70. Shackford S, Collins GM, Kaplan G, Harbach L: Idiopathic ureterolithiasis in a renal transplant patient. J Urol 116:660-661,1976. 71. Loening SA, Banowsky LH, Braun WE, Magnusson MO: Bladder neck contracture and urethral stricture as complications of renal transplantation. J Urol 114:688-691, 1975. 72. Fass RJ, Klainer AS, Perkins RL: Urinary tract infection: Practical aspects of diagnosis and treatment. JAMA 225:1509-1513,1973. 73. Hamshere RJ, Chisholm GD, Shackman R: Late urinary tract infection after renal transplantation. Lancet 2:793-794,1974.

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74. Krieger JN, Tapia L, Stubenbord WT, Stenzel KH, Rubin AL: Urinary infection in kidney transplantation. Urology 9:130-136, 1977. 75. Michigan S: Genitourinary fungal infections. J Urol 116:390-397, 1976. 76. Mathew TH, Kincaid-Smith P, Vikraman P: Risks of vesicoureteric reflux in the transplanted kidney. N Engl J Med 297:414-418, 1977. 77. McMorrow, RG, Curtis JJ, Lucas BA, Williams C, McRoberts JW, Luke RG: Does vesicoureteric reflux result in renal allograft failure? Clin Nephrol 14:89-91, 1980. 78. Anderson B, Sampson C, Callender CO: Spontaneous renal allograft rupture without rejection: A case report. J Urol 115:745-746, 1976. 79. Prompt CA, Johnson WH, Ehrlich RM, Lee DB, Smith RB, Schultze RG: Nontraumatic rupture of renal allografts. Urology 13:145-148,1979. 80. Susan LP, Braun WE, Banowsky LH, Straffon RA, Valenzuela R: Ruptured human renal allograft. Urology 11:53-57, 1978. 81. Haimov M, Glabman S, Burrows L: Spontaneous rupture of the allografted kidney. Arch Surg 103:510-512, 1971. 82. Koostra G, Meijer S, Elema JD: "Spontaneous" rupture of homografted kidneys. Arch Surg 108:107-112, 1974. 83. Lord RS, Belzer FO, Kountz SL: Delayed spontaneous rupture of the allografted kidney. Arch Surg 100:607-610, 1970. 84. Lord RS, Effeney DJ, Hayes JM, Tracy GD: Renal allograft rupture: Cause, clinical features and management. Ann Surg 177:268-273, 1973. 85. Brekke I, Flatmark A, Laane B, Mellbye O: Renal allograft rupture. Scand J Urol Nephrol 12:265-270, 1978. 86. Fjeldborg O, Kim CH: Spontaneous rupture of renal transplant. Scand J Urol Nephrol 8:31-36, 1974. 87. VanCangh PJ, Ehrlich RM, Smith RB: Renal rupture after transplantation. Urology 9:8-10,1977. 88. Penn I: Tumor incidence in human allograft recipients. Transplant Proc 11:10471051, 1979. 89. Penn I, Starzl TE: Malignant tumors arising de novo in immunosuppressed organ transplant recipients. Transplantation 14:407-417, 1972. 90. Frick MP, Salomonowitz E, Hanto DW, Gedgaudas K: Computed tomography of abdominal lymphoma after renal transplantation. AJ R 1 42:97-99, 1984. 91. Matas AJ, Hertl BF, Rosai J, Simmons RL, Najarian JS: Posttransplant malignant lymphomas. Am J Med 61:716-720, 1976. 92. Tubman DE, Frick MP, Hanto DW: Lymphoma after organ transplantation: Radiologic manifestations in the central nervous system, thorax, and abdomen. Radiology 149:625-631, 1983. 93. Ito TY, Martin DC: Tumors of the bladder in renal transplant patients: Report of a case of adenocarcinoma and review of known cases. J Urol 117:52-53, 1977. 94. Birkeland SA, Kemp E, Hauge M: Cancer as a late onset complication of kidney transplantation. Scand J Urol Nephrol 42 (Suppl):179-183,1977. 95. Dubernard JM, Martin X, Neyra P, Touraine JL, Malik MC, Traeger J: Successive appearance of carcinoma, tuberculosis and nephrolithiasis in a renal allograft. J Urol 124:540-542, 1980. 96. Isiadinso OA, Stubenbord WT, Rubin AL: Renal-cell carcinoma post renal transplant. NY State J Med 76:2024-2025,1976. 97. Matas AJ, Simmons RL, Buselmeier TJ, Kjellstrand CM, Najarian JS: Successful renal transplantation in patients with prior history of malignancy. Am J Med 59:791795,1975. 98. Montie JE: The significance of cancer after renal transplantation. J Urol 122:298299,1979. 99. Penn I: The incidence of malignancies in transplant patients. Transplant 7:323-326, 1975.


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100. Penn I: Malignancies associated with renal transplantation. Urology 10 (Supp!):5763,1977. 101. Beachley MC, Pierce JC, Boykin JV, Lee HM: The angiographic evaluation of human renal allotransplants. Arch Surg 111:134-142, 1976. 102. Frodin L, Thorarinsson H, Willen, R: Preanastomotic arterial stenosis in renal transplant recipients: A report of four cases. Scand J Urol Nephrol 9:66-70, 1975. 103. Kiser WS, Hewitt CB, Montie JE: The surgical complications of renal transplantation. SurgClin North Am 51:1133-1140,1971. 104. Murray JE, Tilney NL, Wilson RE: Renal transplantation: A 25 year experience. Ann Surg 184:565-573, 1976. 105. Raphael MJ, Steiner RE, Shackman R, Ware RG: Postoperative angiography in renal homotransplantation. Br J Radiol 42:873-885, 1969. 106. Staple TW, Chiang DTC: Arteriography following renal transplantation. AJR 101: 669-680,1967. 107. Sorenson BL, Hald T, Nissen HM: Silent iliac compression syndrome as a cause of renal vein thrombosis after transplantation. Scand J Urol Nephrol 6 (Suppl):75-77, 1972. 108. Bennett WM, Strong D, Roesch J: Arteriovenous fistula complicating renal transplantation. Urology 8:254-257, 1976. 109. White Rl, Najarian J, Loken M, Amplatz K: Arteriovenous complications associated with renal transplantation. Radiology 102:29-36, 1972.

CHAPTER 7

Nuclear Medicine as an Assessment Technique Merle K. Loken and Salma Mikhail

Our institution initiated renal transplantation as a means for treating patients with kidney failure in 1963. Following successful transplantation of several cadaver kidneys, the program was extended to the use of allografts from donors with attention to pretransplant antibody screening and cross match testing. At this writing 1,529 transplantations have been performed at our institution, with 652 using cadaver kidneys and 877 performed with kidneys from live donors. Of these, 468 were siblings of the recipient. Other donors were parent (263), offspring (99), other related (44), and unrelated (3) donors.

METHODOLOGY From the beginning of our renal transplant program, radionuclides have been used routinely for evaluation of transplant function.

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Tracings or computer-generated curves (renograms) of the uptake and clearance of orthoiodohippuric acid (OIH) has been the hallmark of these studies. The usual intravenous dose of OIH has been 50 fj.C\. For the first 15 years, renograms were obtained using scintillation detectors with rate meters and strip chart recorders. Since that time, these studies have been performed using a scintillation camera fitted with a high-energy collimator and with computer processing of data. For assessment of certain other problems related to renal transplantations, such as vascular compromise, leakage, and obstruction, studies have been performed following the intravenous injection of a bolus of 5-10 mCi of 99m technetium DTPA (diethylenetriaminepentacetic acid) together with a scintillation camera and computer. About 1 2,000 studies have been performed using these technques.1"9 Because of the location of kidney grafts in either or both iliac fossae, the renograms are generally performed with the patients lying supine under the detector. Because either (or both) hypotension and dehydration can produce significant alterations in the renogram pattern, the blood pressure is monitored throughouteach study and a urine specimen is obtained at the termination of each abnormal study for measurement of specific gravity. During our use of scintillation probes for assessing renal function, we often found that the fixed field size of the scintillation probe caused a problem because a portion of the bladder was included in the field of view. Thus we found it desirable to take at least one scintillation camera image of the region of the transplanted kidney at the termination of each study. This picture permitted an adjustment to be made in the interpretation of those renogram curves that included bladder activity. It also provided useful information about other complications of renal transplantation, such as outflow obstruction, urine leak, and the presence of masses like those associated with hematomas or lymphoceles. Because pictorial presentations of changes in the distribution of radioactivity in the renal and perirenal area provide the only reliable means for identifying many of these complications, we have used a camera exclusively for renography and other studies of complications of renal transplantation for the past 5 years. With this technique, serial pictures are obtained at 3- to 5-minute intervals during the course of a 30-minute study. Data are also entered into a computer to permit renogram tracings to be obtained for either the entire kidney or portions of it. The technique allows

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one to select a specific region of the kidney and thus eliminate the problem of "cross talk" from the bladder. This approach has become even more important in recent years as surgeons endeavor to place the transplanted kidney as close as possible to the bladder. If some abnormality exists that delays the clearance of radioactivity from the transplant, scintiphotos are obtained at later times—as late as 24 hours after injection. When outflow obstruction is a possible cause for delayed renal clearance, 20 mg of furosemide is given, followed by an additional 20-30 minutes of data acquisition.

COMPLICATIONS OBSERVED A list of the various complications that we have observed using radionuclide renography are shown in the accompanying tabulation, along with other medical problems presented by transplant patients that have been amenable to study by techniques of nuclear medicine.10"16 Through the years there has been a gradual improvement in the matching of donor kidneys to the recipient, particularly in instances in which live, related donors are used. Better techniques of transplantation as well as of medical management have also improved significantly the continued functioning of the renal allograft and thus the survival of these patients.17'23 Combined results of renal transplantation performed at seven centers during 1977 and 1978 showed the 1-year patient survival rate for recipients of living related and cadaver grafts to be 95.1 and 88.6%, respectively. 20 One-year graft survival rates were 78.6 and 55% for living related and cadaver transplants. Very similar results have been published by the transplant team at the University of Minnesota,17"23 where patients are divided into three groupseras 1, 2, and 3—for purposes of determining survival. During era 1, covering the period from September 1968 to June 1976 for diabetics and from January 1968 to June 1977 for nondiabetics, all patients were splenectomized before or during the kidney transplant. During era 2, from July 1976 to July 1979 for diabetics and July 1977 to July 1979 for nondiabetics, patients were splenectomized randomly; in this era, graft survival rates were lower in nonsplenectomized recipients of cadaver grafts. During era 3, from July 1979 to May 1981 for both diabetic and nondiabetic patients, all patients were splenectomized before transplantation. The data

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clearly show that splenectomy has a favorable effect on survival, both of patients and their grafts. There has also been a gradual improvement in overall survival rate as skills and understanding of the transplantation have progressed. The Minnesota series shows essentially no difference between patient and graft survival in diabetic versus nondiabetic recipients.22 This result is slightly different from that reported by the combined study,20 which found that nondiabetics and their renal grafts survived somewhat better than did diabetic recipients. Complications Observed by Techniques of Nuclear Medicine Renal transplant complications Acute tubular necrosis Nephrotoxicity Rejection, acute or chronic Vascular compromise Arterial stenosis or thrombosis Venous thrombosis Vascular leak (hematoma) Lymphocele Outflow obstruction (ureteral kinking vs. occlusion) Urine leak (urinoma) Reflux Hypotonic pelvis and/or ureter Hypotonic bladder Infection (glomerulonephritis, pyelonephritis, cytomegalovirus) Related medical problems Gastrointestinal bleeding Osteoporosis Aseptic necrosis Pulmonary emboli Systemic infection Tumor induction The complications listed in the tabulation are signficantly less frequent today than they were in the early days of transplantation. The most common complication in the early postoperative period

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continues to be acute tubular necrosis, followed by nephrotoxicity and next by rejection. We have tried to establish techniques that differentiate these complications, particularly acute tubular necrosis (ATM) from rejection. The best way to make this differentiation is to analyze changes in the patterns observed in serial renograms. If the pattern of renal function gradually improves following a transplantation, the most likely situation is the gradual resolution of ATN. If the reverse occurs —if a gradual worsening in the functional pattern is seen following transplantation —the most likely cause is graft rejection, although the use of agents like cyclosporin A (which may be nephrotoxic) can produce a similar renographic pattern. A major difference between rejection and ATN appears related to changes in renal blood flow. Administration of a bolus of an agent like 99m technetium DTPA (or pertechnetate) produces blood flow patterns that are different for these two entities. A significantly greater compromise of renal perfusion tends to be present in cases of rejection than of ATN9)12~16 Various vascular complications can lead to malfunction of kidney transplants.9"16'24"41 We have studied several patients who have exhibited a stenosis or thrombosis of the arterial supply to the kidney. In stenosis, the renogram pattern characteristically shows a delay in extraction as well as clearance of OIH. In severe stenosis, the blood flow may be limited to the extent that an additional complication —that of ATN—ensues. In these cases, the extraction of radionuclide is diminished to the extent that a nearly flat (anephric) pattern is seen. Because diminished renal perfusion and ATN produce similar changes in the renogram pattern, other techniques are needed to help separate these diagnostic possibilities. The administration of an intravenous bolus of an agent like 99m technetium DTPA can be helpful in elucidating the presence of diminished perfusion to a kidney transplant. Since DTPA is subsequently filtered by the glomeruli, a continuous observation of the uptake and clearance of this agent for about 30 minutes may also provide information on glomerular filtration rate and permit an evaluation of any of several complications in renal transplantation. When the blood supply to all or part of a renal transplant is interrupted, infarction is expected to follow. Because total renal artery occlusion or renal vein thrombosis permits no blood flow, hence no localization of radionuclide in the graft, a flat renogram

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will be observed. On the other hand, occlusion of a segmental renal artery in the immediate postoperative period may not be suspected clinically because the pain or hematuria might be assumed to be secondary to the surgery itself. In these instances, 99m technetium DTPA is the agent of choice to be administered as a bolus to demonstrate discrete regional diminution of flow or infarction. Renograms of selected regions of the kidney following OIH administration are also useful in this regard.9'12"16 Postoperative vascular leaks usually produce perirenal hematomas that may be troublesome to diagnose. Without serial scintiphotos, this complication may be mistaken for either rejection or ATM. Hematomas usually produce a photon-deficient region surrounding the renal graft. They often compress the ureter or the bladder and thus obstruct urine flow. A similar situation may be found with the development of a lymphocele. Techniques of nuclear medicine are particularly sensitive in detecting urinary leaks. These leaks are usually evident in the immediate postoperative period, generally at the site of the ureterovesical anastomosis. Sometimes a leak occurs in the renal pelvis from an inadvertent compromise of its integrity during surgery or secondary to improper needle placement during a renal biopsy. Obstruction in the outflow tract has been observed in several of our patients, resulting either from a hematoma or a lymphocele. It may also be caused by edema at the anastomotic site or be secondary to intrarenal hemorrhage with subsequent blood clot formation. This problem may be difficult to differentiate from ATM or from rejection with its attendant dilatation of the ureter. Where scintiphotos suggest obstruction, 20 mg of furosemide is given intravenously and the renogram tracing is continued for another 20-30 minutes. In instances of "pseudoobstruction," radioactivity clears rapidly from a hypotonic pelvis or ureter. In rare instances, iatrogenic enlargement of the bladder may be seen. It may be secondary to urethral obstruction—such as that associated with prostatic enlargement—or to the atropinic effect of certain medications.9 Infection of a renal graft may alter its function. Examples are glomerulonephritis, pyelonephritis, or infections secondary to viral invasions (as by cytomegalovirus).30"33 Studies with labeled leukocytes are helpful in this regard, although the deposition of these labeled cells in the graft may also be seen in instances of rejection.34'35 Others have reported the successful use of 99m techne-

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tium sulfur colloid for this purpose, although this agent has proved to be nonspecific in our hands.8 Other complications that we have studied in renal transplantation include systemic infections, pulmonary emboli, gastrointestinal bleeding, osteoporosis, aseptic necrosis of the femoral head, and tumor induction.36"41 Renal transplant patients are particularly prone to osteoporosis or aseptic necrosis because of the steroids used as part of the postoperative medical regimen. These patients are also quite susceptible to systemic infections and the induction of tumors because of steroids and the action of other immunosuppressive agents, like azotroprine or cyclosporin.

SUMMARY Techniques of nuclear medicine have been found to be very useful in the evaluation of postoperative complications of renal transplantation. Most studies performed at our institution relate to an assessment of graft function, which may be altered secondary to a variety of parenchymal or vascular problems. Studies that assess the integrity of urine flow have also proved clinically useful. Additional complications of transplantation relating to inflammatory processes, tumor induction, embolic disease, osteoporosis, aseptic necrosis, and gastrointestinal bleeding have also been studied using these techniques. More than 12,000 examinations have been performed during the 18 years since kidney transplantation was introduced at our institution. At this writing, 1,529 transplantations have been performed—652 using cadaver kidneys and 877 using kidneys from live donors. Illustrations of the various complications as assessed by radionuclide techniques are presented in figures 7.17.29.

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Figure 7.1. Renogram /4 was obtained in a patient who had been anuric following transplant surgery the day before. Although the tracing indicates extremely poor renal function secondary to severe acute tubular necrosis, this study indicates that the vascular supply to the graft is intact by virtue of the upslope, albeit limited. A film from an arteriogram (B) shows essentially normal perfusion of a transplanted kidney. We have found repeatedly that a renal arteriogram can be

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essentially normal in the presence of a grossly abnormal renogram, as in this instance. Only where renal tubular cells are normal is the extraction of OIH an indicator of renal blood flow. Tubular cell function is markedly compromised here, and the appearance of radioactivity in the kidney is by virtue of passive glomerular filtration. (From Davidson HD, et al.: Am J Roent 105:682-688, 1969. Reprinted by permission.)

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Figure 7.2. Thisscintiphoto (A ), obtained in a patient who had received a cadaver transplant 5 days earlier, shows the typical parenchymal distribution of activity seen in acute tubular necrosis (arrow). A similar pattern might also be seen in diminished renal perfusion, such as that associated with acute rejection. Radiographs B and C from an anteriogram indicate near normal perfusion of the transplanted kidney, indicating (as in the previous case) that acute tubular necrosis is the cause of the abnormal study.

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Figure 7.3. Renogram A was performed within hours of renal transplantation of this patient (HS). One scintillation probe was placed over the graft and the other over the left lower quadrant (LLQ) as a control. There is very gradual rise in radioactivity to a plateau in the transplanted kidney, indicating poor renal function caused either by inadequate perfusion or acute tubular necrosis (or

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both). Five millicuries of 99m technetium (pertechnetate) was then administered intravenously as a bolus (B). Images obtained at approximately 10 and 15 seconds after injection show adequate perfusion of the transplanted kidney again, as in the two previous cases, implicating acute tubular necrosis as the cause of the problem. A repeat renogram performed about 10 days later

7.3. (C) shows essentially normal function, indicating nearly complete resolution of acute tubular necrosis. The probe

Figure 7.4. Three renograms (A) were performed on dates indicated after transplantation. The first is comparable to that seen in the cases presented above, but the cause here is arterial stenosis produced by torsion of the kidney. An arteriogram (B) demonstrates the stenosis at the site of anastomosis between the renal artery and the hypogastric artery. Following corrective surgery on 5 January 1971, renogram patterns (A) improved and approached normal by the third postoperative day 8 January 1971. (From White Rl, et al.: Radiology 102: 29-36,1972. Reprinted by permission.)

placed in LLQ shows some pickup of radioactivity from the adjacent bladder.

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Figure 7.5. Renograms (A) were performed on this patient (BJ) within 2 days of each other. One (left), performed in the immediate postoperative period, shows essentially normal function of the graft. The patient suddenly became anuric on the third postoperative day. The second renogram (right) shows no uptake, suggesting total vascular compromise. A subsequent arteriogram (B) verified occlusion of the site of anastomosis of the artery to the renal transplant. (From White Rl, et a!.: Radiology 102:29-36, 1972. Reprinted by permission.)

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Figure 7.6. Sulfur colloid labeled with 99m Tc (SC) accumulates in renal transplants secondary to various transplant complications. Scintiphotos were taken of four patients, each receiving 2 mCi of SC. Arrows show uptake of radioactivity into transplanted kidney for reasons shown: (A) Acute rejection, (B) chronic rejection, (C) acute tubular necrosis, and (D) normally functioning second trans-

plant during sepsis. Also shown in D is uptake in the first transplant, which is undergoing chronic rejection (x); the tip of right hepatic lobe of the liver (L) is visible. Deposition of SC in renal grafts secondary to various complications illustrates the nonspecificity of this finding. (From Frick MP, et al.: J Nucl Med 17: 181-183, 1976. Reprinted by permission.)

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Figure 7.7. Study performed on a kidney during rejection with a delay in extraction and clearance of OIH from the transplant without evidence of obstruction (gradual rise in radioactivity in the bladder). A study performed with 99m

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technetium sulfur colloid shows the significant uptake of radioactivity with the transplant that may be seen in cases of chronic rejection (figure 7.6) as well as in other complications of renal transplantation.

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Figure 7.8. Four sequential renograms following renal transplantation. Three of these (A-C) also include scintiphotos obtained at the conclusion of each study. The sequence shows typical findings associated with a gradual resolution of acute tubular necrosis. As renal function

improves, increasing quantities of radioactivity are present in the bladder at the termination of the 30-minute study. The acute tubular necrosis was initially quite severe, as reflected by the time (about 6 weeks) required for the kidney to approach normal function.

Nuclear Medicine

Figure 7.9. Another example of acute tubular necrosis (A), complicated in this case by distal ureteral necrosis and the formation of a urinoma on the fourth postoperative day (B). A normal renographic tracing was obtained following nephrostomy (C). Because of the ne-

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phrostomy drainage, no radioactivity appears in the bladder. The acute tubular necrosis in this patient was not nearly as severe as that shown in the previous case; consequently, the resolution to normal occurred more rapidly after correction of the urine outflow problem.

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Figure 7. JO. The initial renogram obtained 24 hours after a renal transplant in this patient is normal (A ). Severe acute rejection that occurred during the third postoperative week (B) slowly responded to antirejection therapy (C). In acute rejection, the first change that is noted in the renogram is an elevation of the descending limb. If the rejection continues, a gradual decrease in the rate of extraction (ascending limb) follows. Without appropriate adjustments in medical man-

agement of these patients, the renogram pattern may progress to a flat (anephric) pattern. As the kidney responds to antirejection treatment, the return toward normal is the reverse of the pattern indicated by the curves in B and C. Two pictures from an arteriogram performed during rejection are shown in D. There is evidence of pruning (blunting) of the arterial tree, with subsequent diminution in blood flow.

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Figure 7.11. Renogram A shows normal extraction, with evidence of intermittent outflow obstruction; the study is otherwise normal. A subsequent renogram (B) shows continuation of near normal extraction but with a persistent delay in

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clearance. The scintiphoto accompanying the study shows retention in the renal parenchyma rather than in a renal pelvis, indicating a rejection superimposed on a partial obstruction.

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Nuclear Medicine Figure 7.72. Tracing A was obtained on 10 January 1975 in a patient who had received two renal transplants at different times in the past. This study shows that the initial transplant (old R kidney) appears to be functioning somewhat better than that on the left (new L kidney). The latter exhibits significant retention of OIH within the parenchyma,suggestive of acute tubular necrosis in the immediate postoperative period. A sulfur colloid scan performed at the same time shows essentially no uptake of radioac-

Figure 7.13. Scintiphoto A shows collection of leukocytes labeled with Indium111 in the transplanted kidney as seen in rejection or inflammation. The uptake here was secondary to rejection, which was confirmed by the retention of 99m

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tivity in the newly transplanted left kidney but significant uptake on the right, suggestive of rejection of the first transplant. This was confirmed by a later study on 15 January (B) showing significant deterioration in the function of the first transplant. There is concomitant slight improvement during this 5-day period in the functioning of the kidney transplanted to the left lower quadrant, indicating a gradually resolving acute tubular necrosis.

technetium DTPA on scintiphoto B, indicating significant compromise in renal function. (From Forstrom LA, et al.: Clin Nucl Med 6:146-149, 1981. Reprinted by permission.)

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Figure 7.14. (A) Deposition of leukocytes labeled with lndium-111 24 hours after injection of 350 juCi of radioactivity in a 50-year-old male who had received a kidney transplant some months earlier. The postoperative period was complicated by a cytomegalovirus infection producing the infiltrate of the right lung as shown in radiograph B. The patient

Figure 7.75. Posterior view of the thorax and abdomen of a renal transplant patient with a cytomegalovirus infection but without any compromise in renal function. This study shows even greater uptake of radioactivity in both lungs than in the case shown in figure 7.14 because there is more widespread involvement of the viral infection. The small amount of radioactivity in the spine and the sacroiliac joints is indicative that some of the Indium not labeled in vitro to leukocytes has become labeled spontaneously to transferrin in vivo and thus has migrated into the bone marrow.

had had a splenectomy at the time of placement of the renal graft. Deposition of radioactivity in the liver is a normal finding, whereas the localization of labeled cells in the lungs —primarily on the right side —is abnormal and indicates an inflammatory process. (From Forstrom LA, et al.: Clin Nucl Med 6:146-149, 1981. Reprinted by permission.)

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Figure 7.16. Anterior and posterior scans obtained in a patient (MK) who had received a kidney transplant in March 1979 because of chronic renal failure. The patient later had repeated febrile episodes, during which several lndium-111 leukocyte studies were performed. Three stud-

Figure 7.77. Studies obtained on a 64year-old female (RS) with a clinical history of malabsorption syndrome and polycystic kidneys. A bilateral nephrectomy and splenectomy were performed at the time of renal transplantation in 1972. On 6 Feburary 1979, exploratory laparotomy revealed peritonitis secondary to a gastric perforation. Therapy with antibiotics was commenced. One week later, a scan using 99m technetium sulfur

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ies showed recurring uptake of radioactivity within the lungs consistent with a cytomegalovirus infection; none of these studies showed abnormal foci of radioactivity within the abdomen. In October 1979, the patient developed a necrotizing cholecystitis requiring a cholecystectomy. Subsequently, the patient developed a biliary fistula. Because of persistent fever the patient was explored in April 1980, when an infected hematoma was drained from the left upper quadrant. Four sequential Indium studies were then performed, all of which showed a collection of radioactivity in the left upper quadrant indicating persistent inflammatory foci in this location. Scans obtained from the third of these studies on 2 May 1980 show at least two foci of abnormal activity anteriorly in the region of the epigastrium and (arrows) posteriorly into the retroperitoneal space (arrow}.

colloid revealed a normal-appearing liver. A study with 394 juCi of lndium-111 labeled leukocytes showed several sharp foci of increased activity in the region of the left upper quadrant of the abdomen (arrows), with a slight concentration of radioactivity in the region of the myocardium. These foci indicate inflammatory disease in this patient with a normally functioning kidney transplant.

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A

Figure 7.18. Scans (/I) obtained in the anterior and posterior projections following administration of 350 juCi of Indium-111 labeled leukocytes in a renal transplant patient who had a splenectomy performed concomitantly with a transplant. The posterior view shows a sharp focus of increased activity in the left upper quadrant that could represent an inflammatory focus. The patient then received 3 mCi of 99m technetium sulfur colloid: scintiphoto obtained of the left

upper quadrant and posterior projection is shown in B (left). The left lobe of the liver is visualized, and to the left of the liver a sharp focus of radioactivity defines an accessory spleen. With the patient in the same position, the discriminator of the camera was shifted to encompass the energy peak for lndium-111 and a second scintiphoto was obtained (right). The correspondence of the location of the radioactivity in both images verifies the presence of an accessory spleen.

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Figure 7.79. Three scintiphotos taken 5, 15, and 30 minutes after injection show normal function immediately after transplantation in patient GM. Urine is not retained in the bladder because of catheter placement. The computerized renogram illustrates the rapid extraction and

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clearance of OIH from the graft. This represents a normal study using a scintillation camera and computer. The picture in the lower left illustrates the selection of regions of interest (kidney and bladder).

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Figure 7.20. Scintiphotos (A) obtained during two renograms performed 1 week apart on patient AR. The study on 11 February shows normal extraction with significant parenchyma! retention but with passage of radioactivity into the bladder, thus ruling out obstruction as a problem. In the early postoperative period, this finding most likely represents acute tubular necrosis. One week later the extraction of OIH has been diminished, with very minimal appearance of radioactivity in the bladder at 1 5 minutes. The corresponding renographic patterns for these two studies are shown in B. Deterioration in the pattern seen on 18 February indicates acute rejection superimposed on acute tubular necrosis.

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Figure 7.27. These studies were obtained on a 46-year-old male (CB) who received a related donor transplant on 13 February 1979. Scintiphotos from two subsequent studies are shown in A. The first, performed on the day following transplantation, shows prompt uptake and clearance of radioactivity with only minimal retention in the renal pelvis at 30 minutes; slight retention of radioactivity in the renal collecting system and ureter suggests minimal postoperative edema at the site of implantation of the ureter. A study performed about 5 weeks later shows that the extraction as well as clearance of radioactivity from the graft have diminished. The appearance of radioactivity in the bladder indicates that the outflow tract is intact and that no significant obstruction exists. Corresponding renograms (redrawn) are shown in B. The tracing obtained on 14 Feburary 1979 is normal, whereas the second study indicates the onset of a relatively severe rejection. The patient was hospitalized and treated. Subsequent renograms gradually improved as the acute rejection resolved.

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T.H. 4-20-78

T.H. 5-26-78

B

Time

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Figure 7.22. Studies (A, B) were performed on this 21-year-old male (TH) 1 and 6 weeks following transplantation of a kidney from a related donor. The study performed on 20 April 1978 is essentially normal. Minimal retention of radioactivity in the renal pelvis 30 minutes after administration of OIH suggests some pelvic hypotonicity. The study performed on 26 May 1978 indicates that although extraction of radioactivity remains quite good, there is a significant delay in clearance of Hippuran from the kidney as well as a delay in its appearance in the bladder. The scintiphotos ( A ) indicate retention of radioactivity in a dilated pelvis and ureter, suggesting partial obstruction at the site of insertion of the ureter into the bladder. Film from an intravenous pyelogram (C) shows contrast media in the dilated calicesand pelvis of the graft.

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B QRU

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Figure 7.23. Scintiphotos (A) and renograms (B, C) obtained on a 20-year-old male with juvenile onset diabetes mellitus during studies carried out 6 months and 2.5 years after transplantation. The study performed on 2 January 1980 shows only minimal parenchymal retention at 30 minutes, indicating essentially normal function. The study performed on 28 April 1982 also indicates good renal func-

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tion but provides evidence that radioactivity is being retained in a somewhat dilated pelvis and ureter, suggesting the development of partial obstruction involving the distal ureter. The scintiphotos show that the graft has an unusual orientation, with its long axis lying transversely and its pelvis projecting inferiorly.

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B Figure 7.24. These studies, performed on the second cadaver transplant into this patient (PS), illustrate the difficulty in evaluating grafts having an intrarenal pelvis. The patient was initially transplanted on 21 September 1970 with a graft placed in the right iliac fossa and did well for about 5 years, when an irreversible rejection of the graft occurred and a nephrec tomy was performed. A second transplant was performed on 20 June 1977, with the graft placed in the left iliac fossa. Except for minimal acute tubular necrosis after the operation that cleared within 1 week, the graft functioned normally. On 4 September 1981, renography indicated normal extraction with minimal retention

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in the renal parenchyma but some residual radioactivity in the intrarenal pelvis, which partially overlies the lower pole of the graft. By careful selection of the region of interest, the computer-generated renogram tracing is within normal limits. On a repeat study on 28 April 1 982, extraction continues to be essentially normal; however, significant dilatation of the pelvis and ureter interferes with assessment of renal function. The amount of radioactivity reaching the bladder is diminished because of the partial obstruction. The scintiphotos for both studies are identified by dates in A; the corresponding renograms are shown by dates in B.

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Figure 7.25. These studies were performed on a 35-year-old male who received a cadaver renal transplant on 4 May 1978. Significant acute tubular necrosis gradually lessened over the next several weeks. The study performed on 1 January 1980 shows essentially normal extraction of OIH but with minimal retention of radioactivity within the renal parenchyma at 30 minutes,which suggests the onset of a mild rejection of the graft. This finding was further substantiated by a diminution in the patient's creatinine clearance. A repeat examination on 4 May 1978 indicates improvement in renal function, with only a small amount of OIH being retained in the renal pelvis at the completion of the study. The graph, however, is similar to that obtained on the earlier study because in both instances the entire kidney and pelvis were selected as the area of interest. Scintiphotos are thus an important addition to tracings when interpreting renal function. The tracings of "bladder" activity also indicate that it is unchanged between the two studies, but the scintiphoto of the distribution of radioactivity in the region of the bladder suggests some extravasation of urine. This interpretation was confirmed by other studies.

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Time Figure 7.26. Scintiphotos (A} obtained 5, 15, and 30 minutes after injection of patient SD on 18 September 1978. The extraction of OIH appears to be essentially normal, as is the transit time of the radioactivity through the graft. However, activity is either retained in the pelvis or partially refluxed from the bladder into the pelvis during the re-

mainder of the study. The 30-minute picture also shows evidence of reflux into the left native ureter of this patient. The corresponding renogram (B;redrawn) for patient SD is also shown.The unusual shape of the latter portion of the bladder curve (slight downslope) probably reflects the reflux of radioactivity out of the bladder into the native ureter.

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Figure 7.27. A renal flow study performed with 10 mCi of 99m technetium DTPA and a concomitant renogram with OIH were performed 6 weeks after patient CC received a second cadaver transplant. Scintiphotos obtained 2, 4, and 6 seconds after the appearance of radioactivity in the abdominal aorta show good perfusion of the graft (top panel of A). The OIH portion of the study indicates

good extraction of radioactivity by the transplanted kidney. A very large avascular area surrounding the graft represents a large lymphocele that produced a significant outflow obstruction such that minimal radioactivity was delivered into the bladder at 30 minutes (lower panel of A). The corresponding renogram tracing is shown in B.

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B

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C.C. 11-26-79

Figure 7.28. A chest radiograph (A) obtained on 13 April 1982 of this febrile patient with known cytomegalovirus infection is essentially normal except for very mild cardiomegaly. On 21 April 1982, the patient received 20 mCi of 99m technetium labeled erythrocytes for investigation of gastrointestinal bleeding.

Scintiphotos (A-D) obtained 15 minutes and at 1, 5, and 24 hours after administration of the labeled erythrocytes show the gradual accumulation of radioactivity in the cecal region. At 24 hours, activity is seen throughout the cecum and large bowel. The study illustrates cases where patients develop gastrointestinal bleeding secondary to a cytomegalovirus infection.

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Figure 7.29. Patient DC, a 35-year-old male, received a renal graft with the outflow attached to an ileal loop in August 1976. A renogram (A) was performed on 7December1977 with scintillation probes placed over the graft and the collection bag. There is good extraction, with an indication of some delay in clearance of activity from the graft. Because of the proximity of the ileal loop to the graft, a scintiphoto (insert) was obtained at 30 minutes. It shows that essentially all of the radioactivity has passed into the loop, indicating near normal graft function. A film (B) from an IVP performed the following day shows contrast passing into the loop and collection bag, again indicating good renal function. This radiograph also shows the presence of severe aseptic necrosis involving the right femoral head and acetabulum.

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7.29. A pelvicfilm obtained some months later (C) shows that both hips are severely involved with aseptic necrosis. About

a year later, the patient was fitted with bilateral hip prostheses.

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REFERENCES 1. Loken MK, Staab EV, Vernier RL, Kelly WD: Radioisotope renogram in kidney transplants. J Nucl Med 5:807-810,1964. 2. Loken MK, Stejskal RE, Amplatz K: The use of radioisotopic techniques for the evaluation of renal disease. University of Minnesota Medical Bulletin 35:236-239, 1964. 3. Staab EV, Kelly WD, Loken MK: Prognostic value of radioisotope renograms in kidney transplantation. J Nucl Med 10:1 33-135,1969. 4. Davidson HD, Loken MK, Amplatz K: Isotope renography and renal arteriography in the evaluation of renal transplants. Am J Roent 105:682-688,1969. 5. Loken MK, Linnemann R, Kush G. Evaluation of renal function using a scintillation camera and computer. Radiology 93:85-94, 1969. 6. White Rl, Najarian J, Loken MK, Amplatz K: Arteriovenous complications associated with renal transplantation. Radiology 102:29-36, 1972. 7. Williams LE, Merion GE, Goren C, Najarian JS, Loken MK: Detection of canine kidney allograft rejection with 51-Cr labeled leukocytes. Radiology 115:205-206,1975. 8. Frick MP, Loken MK, Goldberg ME, Simmons RL: The use of 99m-technetium sulfur colloid in the evaluation of the function of renal transplants. J Nucl Med 1 7:181 183,1976. 9. Ayres JG, Hilson A J W , Maisey MN: Complications of renal transplantation: Appearances using Tc-99m-DTPA. Clin Nucl Med 5:473-480, 1980. 10. Zum Winkel KE, Harbest H, Doss KB, Newiger T: Applications of radionuclides in renal transplantation. Semin Nucl Med 4:1 69-1 86, 1974. 11. Dubovsky EV, Logic J R, Diethelm AG, Balch CM, Tauxe WN: Comprehensive evaluation of renal function in the transplanted kidney. J Nucl Med 1 6:1115-1120, 1975. 12. Clorius JH, Dreikorn K, Zelt J, Raptou E, Weber D, Rubinstein K, Dahm D, Georgi P: Renal graft evaluation with pertechnetate and 1-131 Hippuran. A comparative clinical study. J Nucl Med 20:1029-1 037,1979. 13. Preston DF, Luke RG: Radionuclide evaluation of renal transplants. J Nucl Med 20: 1095-1097, 1979. 14. Bischof-Delaloye A, Wauters JP, Brunner H R, Delaloye B: Appreciation of renal function by IOH with the scintillation camera after kidney transplantation. IAEA-SM-247/ 107 Medical Radionuclide Imaging, Heidelberg, 1-5 September 1980; 377-385. 15. Sampson WFD, Macleod MA, Warren D: External monitoring of kidney transplant function using Tc-99m (SN) DTPA. J Nucl Med 22:411-416, 1981. 16. Shanahan WS, Klingensmith WC, Weil R: 99m-Tc-DTPA renal studies for acute • tubular necrosis: Specificity of dissociation between perfusion and clearance. Am J Roentgenol 136:249-253, 1981. 17. Najarian JS, Kjellstrand CM, Simmons RL: High-risk patients in renal transplantation. Transplant Proc9:107-111, 1977. 18. Najarian JS, Sutherland DER, Simmons RL, Howard RJ, Kjellstrand CM, Ramsay RC, Goetz FC, Fryd DS, Sommer BG: Ten year experience with renal transplantation in juvenile onset diabetics. Ann Surg 190:487-500,1979. 19. Marshall V: Renal transplantation—fifteen years experience. Br j Surg 68:1-6,1981. 20. Standards Committee of the American Society of Transplant Surgeons: Current results and expectations of renal transplantation. JAMA 246:1330-1336,1981. 21. Fryd DS, Sutherland DER, Simmons RL, Ferguson RM, Kjellstrand CM, Najarian JS: Results of a prospective randomized study on the effect of splenectomy versus no splenectomy in renal transplant patients. Transplant Proc 13:48-56, 1981. 22. Sutherland DER, Fryd DS, Morrow CE, Ferguson RM, Simmons RL, Najarian JS: The high risk recipient in renal transplantation. Transplant Proc 14:19-27,1982.

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23. Morrow CE, Fryd DS, Sutherland DER, Najarian JS: Improved primary renal allografts survival in diabetic recipients. Forthcoming. 24. Steensma-Vegter AJ, Krediet RT, Westra D, Tegzess AM: Reversible stenosis of the renal artery in cadaver kidney grafts: A report of three cases. Clin Nephr 1 5:102-106 1981. 25. Oakes DD, Spees EK Jr, Light JA: Renal vascular hypertension after transplantation of a kidney perfused via multiple renal arteries. Am Surg 47:272-274, 1 981. 26. Mettler FA, Christie JH: The scintigraphic pattern of acute renal vein thrombosis. Clin Nucl Med 5:468-470, 1980. 27. Krieger JN, Stubenbord WT, Vaughan ED Jr: Transplantation in children with end stage renal disease of urologic origin. J Urol 124:508-512, 1980. 28. McMorrow RG, Curtis J J , Lucas BA, Williams C, McRoberts JW: Does vesicoureteric reflux result in renal allograft failure? Clin Nephr 14:89-91,1980. 29. Mitterdorfer AJ, Williams G, Castro JE: Vesicoureteric reflux following renal transplantation: A simple method of ureteric implantation. Br J Urol 53:111 -114, 1981. 30. Press MR, Riddell RH, Ringus J: Cytomegalovirus inclusion disease. Its occurrence in the myenteric plexus of a renal transplant patient. Arch Pathol Lab Med 104:580583,1980. 31. Fryd DS, Peterson PK, Ferguson RM, Simmons RL, Balfour HH Jr, Najarian JS: Cytomegalovirus as a risk factor in renal transplantation. Transplantation 30:436439,1980. 32. Marker SC, Howard RJ, Simmons RL, Kalis JM, Connelly DP, Najarian JS, Balfour HH Jr: Cytomegalovirus infection: A quantitative prospective study of three-hundred twenty consecutive renal transplants. Surgery 89:660-671,1981. 33. Richardson WP, Colvin RB, Cheeseman SH, Tolkoff-Rubin NE, Herrin JT, Cosimi AB, Collins AB, Hirsch MS, McCluskey RT, Russell PS, Rubin RH: Glomerulopathy associated with Cytomegalovirus viremia in renal allografts. N Eng J Med 305:57-63, 1981. 34. Forstrom LA, Loken MK, Cook A, Chandler R, McCullough J: ln-111-labeled leukocytes in the diagnosis of rejection and Cytomegalovirus infection in renal transplant patients. Clin Nucl Med 6:146-149, 1981. 35. Peterson PK, Balfour HH Jr, Fryd DS, Ferguson RM, Simmons RL: Fever in renal transplant recipients: Causes, prognostic significance and changing patterns at the University of Minneosta Hospital. Am J Med 71:345-351, 1981. 36. Fenech A, Nicholls A, Smith FW: Indium (111-ln)-labeled platelets in the diagnosis of renal transplant rejection: Preliminary findings. Br J Rad 54:325-327,1 981. 37. Breed A, Chesney R, Friedman A, Gilbert E, Langer L, Lattoraca R: Oxalosis-induced bone disease: A complication of transplantation and prolonged survival in primary hyperoxaluria. J Bone Joints Surg 63A:310-316,1981. 38. Gokal R, Kettlewell M, Drexler E, Oliver DO, Morris PJ: Gastrin levels in chronic renal failure, hemodialysis and renal transplantations. Clin Nephr 14:96-97, 1980. 39. Schiessel R, Starlinger M, Wolf A, Pinggera W, Zazgornik J, Schmidt P, Wagner O, Schwarz S, Piza F: Failure of cimetidine to prevent gastroduodenal ulceration and bleeding after renal transplantation. Surgery 90:456-458,1981. 40. PerrottCA, Botha JR, Meyers AM, Myburgh J A : Peptic ulceration in the renal transplant patient. S African Med J 59:253-255, 1981. 41. Stuart FP, Reckard CR, Schulak JA, Ketel BL: Gastroduodenal complications in kidney transplant recipients. Ann Surg 194:339-344, 1981.

CHAPTER 8

Angiographic Evaluation W R. Castaneda-Zuniga

Failure of a transplanted kidney may be caused by any of several factors requiring different methods of management. It is thus necessary to distinguish between rejection, acute tubular necrosis, obstruction of the main blood vessels in the graft, and obstruction of the ureter. Careful evaluation is particularly important when cadaver kidneys are used, for which the functional 2-year survival rate is only 40-50%, compared with 70-80% for living related donor kidneys.1"2 Formerly, renal transplant angiography was often performed to differentiate between acute rejection and acute ischemic tubular necrosis as the cause of graft dysfunction in the immediate postoperative period. Now, however, angiography for the patient with a failing graft is restricted mainly to the search for renal artery stenosis and arterial or renal vein thrombosis. Although the study may be specific when a full-blown pattern of rejection is present, routine angiography has proved to be of little value when rejection is suspected.

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The normal renal transplant arteriogram consists of three phases: arterial, nephrographic, and venous. The arterial phase lasts an average of 1.5 seconds to a maximum of 3 seconds after injection in a selective study. The main renal allograft artery and the interlobar, arcuate, and interlobular arteries appear well filled, with smooth contours (fig. 8.1). Vessels at the arteriolar and capillary levels are not demonstrated by conventional radiographic techniques.

Figure 8.1. (A) Iliac artery injection reveals normal flow through the transplanted renal artery, with an excellent visualization of the lobular, interlobular, and arcuate renal artery branches.

8.1. (B) Nephrographic phase reveals a dense, homogeneous opacification of the kidney with sharp definition of the corticomedullary junction. The thickness of the renal cortex is cleary seen.

8.2. The venous face reveals a dense parenchymal staining with a normal cortical width and beginning of opacification of the renal vein.

Angiographic Evaluation

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The nephrographic phase reveals dense, homogeneous opacification of the kidney with a sharp definition of the corticomedullary junction. The thickness of the renal cortex can be measured accurately (fig. 8.2). The venous phase shows the filling of the renal veins in the hilus of the kidney, merging into the main renal vein (fig. 8.3). Contrast medium excreted by the kidney is visible in the ureter and bladder.

Figure 8.3. Venous phase showing filling of the intrarenal veins that converge

toward the hilus of the kidney, merging into the main renal vein.

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GRAFT DYSFUNCTION Renal allograft dysfunction can be caused by vascular, parenchymal, or urologic complications. Angiography is most useful in diagnosing vascular and parenchyma! disorders. Vascular Complications Vascular complications have been reported with an incidence of 414%.3~6 They may involve the aorta;the common iliac, hypogastric, or renal arteries; or the renal or iliac veins. With improvements in surgical techniques, these complications are less commonly seen at the present time. Angiography plays an important role in the evaluation of these vascular problems, which are commonly manifested by marked decrease in graft function or by hypertension. One of the most common conditions of this group is stenosis, which occurs at various locations: the aorta; the common, external, and internal iliac arteries; the anastomotic site; and the renal allograft artery proper. Incidence of stenosis varies from 1 to 12%.3~7 Other vascular problems are renal or iliac vein thrombosis; postbiopsy renal arteriovenous fistula; and occasional thrombosis of the renal , internal, or external iliac artery. Overall incidence of these problems is 12%.3-W

Obstructive lesions of the aorta and the common, external, and internal iliac arteries may produce hypertension and decreased renal function. Posttransplantation hypertension can also result from retention of water and sodium as a consequence of poor transplant function. It can also accompany treatment of acute or chronic rejection with large doses of corticosteroids because of the increased resistance in the renal vascular system. In these cases, hypertension usually disappears when the rejection episode is under control and the corticosteroid dosage can be decreased.10 The obstruction can be due to atheromatous lesions (fig. 8.4) or to the surgical procedure: for example, injury to the vascular wall by a surgical clamp (fig. 8.5), intimal flaps as a consequence of endarterectomy of the internal iliac artery (frequently done before the anastomosis of this vessel with the allograft artery), or torsion of the vascular pedicle (fig. 8.6). Obstruction may also be caused by extensive compression of the vascular pedicle by extrinsic fluid collection, such as lymphoceles, urinomas, hematomas, or abscess

A ngiographic Evaluation

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(fig. 8.7); compression by pseudoaneurysm at the level of the vascular anatomosis, commonly mycotic (fig. 8.8); and stenosis secondary to rejection vasculitis.

Figure 8.4. (A) Injection of the ipsilateral femoral artery shows patency of the anastomosis and adequate flow into the renal allograft; there is no reflux of contrast medium to the common iliac artery. Extensive calcifications are observed

over this artery (arrows). (B) Injection from the opposite side demonstrates narrowing of the common iliac artery (arrows) due to atheromatous plaques. This patient had a slow developmentof hypertension 4 years after the transplant.

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Figure 8.5. Patient with onset of hypertension 1 month after transplant. (A } Injection in the right common iliac artery shows a radiolucent shadow over the takeoff of the hypogastric artery that represents an intimal flap secondary to the endarterectomy performed at the time of surgery (small arrow). A very regular, smooth stenosis is observed at the level of the anastomosis between the hypogastric and the renal allograft arteries (solid arrow). At the time of surgery, an extrinsic band was found to be causing obstruction at this level. Observe the complete obstruction of the external

iliac artery secondary to the surgical procedure (open arrow). (B) Angiogram after surgical repair shows the presence of marginal irregularities over the proximal common iliac artery, secondary to the placement of a clamp at the time of surgery (arrow). The intimal flap in the hypogastric artery has disappeared after it was sutured at the time of surgery. Observe now a wide open anastomosis between the hypogastric and the renal allograft arteries, with normal visualization of the intrarenal branches. There is complete obstruction of the right external iliac artery.


Figure 8.6. Patient with hypertension after renal transplant. Renal transplant arteriogram performed in anteroposterior (A) and left posterior (B) projections failed to expose the level of the anastomosis, obscuring in this way the demonstration of a stenosis. Observe the stump

Figure 8.7. (A) Arteriogram in the 8th day after transplant reveals a homogeneous mass density occupying the right lower quadrant of the abdomen and displacing the common and external iliac artery downward and toward the left. The kidney is displaced upward and toward the midline. Observe very slow flow

20 7

of the hypogastric artery (A, white arrow). (C) Right posterior oblique demonstrates a severe stenosis at the level of the anastomosis of the renal allograft artery with the external iliac artery because of severe kinking of the renal allograft (arrow).

through the renal artery (arrow). (B) Arteriogram performed 24 hours after exploratory laparotomy where a large hematoma was drained from the right lower quadrant reveals the renal allograft in its normal position and normal flow through the renal artery.

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Figure 8.8. Injection in the right common iliac artery reveals the presence of three large sacular collections of contrast medium overlying the renal allograft ar-

tery. Observe some impairment of flow toward the middle and lower segments of the kidney because of compression by these large mycotic aneurysms (a).

Angiography is also important for demonstrating stenosis in the renal allograft artery (fig. 8.5) or one of its primary branches. True stenosis may be caused by endothelial lesions resulting from cannulation of the renal artery for extracorporeal perfusion, complications of the surgical procedure, or local ischemic atrophy caused by lesions of the vasa vasorum.11 Some constriction or mural irregularity at the anastomosis should be regarded as normal, particularly in end-to-end anastomosis. In fact, it has been said that endto-end anastomoses are obsolete because they have a higher incidence of complications.11 However, the end-to-side anastomosis is not free of complications, as can be seen in figure 8.9.


Figure S.9. Right common iliac artery injection performed in patient with hypertension after renal transplant reveals an end-to-side anastomosis between the renal allograft artery and the right external iliac artery. Observe narrowing of

209

the external iliac artery at the level of the anastomosis, as well as a mild narrow ing at the takeoff of the renal allograft artery (arrows). Observe also slow flow through the intrarenal branches.

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Even with severe, progressive stenosis of the renal allograft artery, collateral flow rarely develops, probably because all major collateral sources (ureteric, capsular, suprarenals, and lumbars) are severed at the time of transplantation. Occasionally, however, intrarenal collateral flow can be observed (fig. 8.10). A large extrarenal collateral vessel communicating with the obstructed segmental renal artery was also observed in this patient. A similar finding has been reported by another observer (DP Harrington, personal communication, 1982).

Figure 8. 70. (A ) Injection in the common iliac artery demonstrates a renal allograft with two segmental arteries, the upper one with a termino-terminal anastomosis with the hypogastric artery and the lower one anastomosed in an end-to-side fashion to the external iliac artery. Observe good flow into both renal arteries and obstruction of the external iliac artery, (fi) Follow-up arteriogram performed because of graft dysfunction demonstrates pa-

tency of the lower renal artery and obstruction of the upper renal branch anastomosis with the right hypogastric artery. There is reconstitution of the upper renal branch via intrarenal collaterals (small arrows). Observe also the presence of a branch of the last lumbar artery, which seems to connect with the upper renal artery in its hilar segment (large arrows).


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Venous obstruction is an uncommon condition that can be either primary or secondary to rejection or to extensive compres sion by pelvic fluid. Pure renal rein thrombosis is a surprisingly rare complication.10'11 Selective phlebography is carried out after arterial angiography whenever there is unmistakable retardation of arterial flow, in an effort to exclude thrombosis on the venous side of the transplant. Venous obstruction may be suspected strongly when severe proteinuria is combined with reduced renal output. In these cases, catheterization should be carried out on the ipsilateral side. First, patency of the femoral and large pelvic veins is established by a test injection of contrast medium at the level of the puncture. Contrast medium is next injected at the site of the anastomosis; if reflux into the renal vein is demonstrated, a selective study is performed. The thrombus can be visible as a persistent radiolucency or as a mural irregularity. Far peripheral filling of the branches of the renal vein signifies marked retardation of arterial flow as a result of rejection process (fig. 8.11). Renal vein thrombosis may be extensive (fig. 8.12) or may involve primarily the iliac vein (fig. 8.13A). Infrequently, venous collateral channels develop between the graft and the host (fig. 8.13B).12

Figure 8.11. (A) Arteriogram in patient with anuria 8 days after transplant demonstrates slow flow and absence of opacification of peripheral branches. (B) Iliac venogram demonstrates excellent retro-

grade opacification of the renal vein, with far peripheral filling of intrarenal venous branches as a manifestation of very slow arterial flow because of the rejection process.

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Figure 8.12. Iliac venogram in patient with renal transplant demonstrates a radiolucent filling defect over the medial side of the iliac vein (arrow] at the level of the anastomosis between the hypogastric vein and the renal allograft vein in patient with renal vein thrombosis.

Figure 8.13. (A ) Injection in the common femoral vein demonstrates the presence of extensive fresh thrombi involving the common femoral, external iliac, and common iliac veins (arrows).


8.73. (B) Stenosis of renal allograft vein with development of collaterals from the

213

graft to pelvic and lumbar veins (arrows).

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Figure 8.14. Patient with postbiopsy arteriovenous fistula of the kidney. Renal transplant arteriogram demonstrates the presence of a saccular, bilobular collec-

tion of contrast medium overlying the lower pole of the kidney with early venous opacification (arrows).

Another less common complication is a postbiopsy arteriovenous fistula in the graft. These fistulas, which may or may not be of hemodynamic significance, are most frequently asymptomatic (fig. 8.14). Thrombosis of the renal (fig. 8.15), external (fig. 8.5), or internal iliac arteries (fig. 8.16) is rarely seen at the present time because of improvement in the surgical techniques. Angiography will demonstrate the site of the vascular occlusion. 3 ~ 5 - 8 ' 9

A nglographic Evaluation

Figure 8.15. (A) Marked narrowing of the end-to-side anastomosis between the renal allograft artery and the right common iliac artery (arrow). (B) Repeat arteriogram following surgical attempt to correct the renal artery stenosis demonstrates extensive thrombosis of the right

Figure 8.16. Injection in right common iliac artery demonstrates complete obstruction of the end-to-end anastomosi between the hypogastric and the renal artery 12 hours after transplant (arrow).

215

common iliac artery (large arrow) and severe stenosis of the renal artery (small arrow). Observe the presence of fresh thrombi beyond the area of stenosis (open arrow) and very slow flow through the intrarenal branches.

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Parenchymal Complications Among the parenchymal complications causing graft dysfunction are allograft rejection, acute tubular necrosis, and renal papillary necrosis. Renal allograft rejection can be classified as hyperacute, acute, or chronic depending on the time and form of presentation. The primary target of rejection is the vascular endothelium.13 Hyperacute rejection occurs when the recipient has produced specific circulating antibodies against the donor's lymphocytes. It is infrequent since the requirement that a final cross match between donor lymphocytes and recipient serum be negative immediately before transplantation. Hyperacute rejection is usually manifested by intravascular coagulation with vascular necrosis and nonperfusion at the time of surgical anastomosis. The onset, however, may be delayed several hours. In this event, it must be differentiated from vascular thrombosis and occlusion at the anastomotic site. Features reminiscent of arterial thrombosis have been observed in hyperacute rejection as a result of massive intravascular coagulation.10'14 Characteristically, the angiogram will show attenuation or obliteration of intrarenal vessels, with an absent or blotchy nephrogram (fig. 8.17). Severe ischemic cortical damage to the kidney at the time of transplantation, resulting in acute cortical necrosis, cannot be distinguished from hyperacute humoral rejection except by the detection of circulating antibodies against donor lymphocytes. 14 Acute rejection may occur at any time, but it is most frequent within 3-14 days after transplantation. It is associated with tenderness and swelling of the graft, fever, oliguria, and acute deterioration of renal function. Acute rejection must be differentiated from acute tubular necrosis, particularly in cadaver kidney transplants. Other diagnoses that must be ruled out are necrosis or leakage of the newly implanted ureter, urinary tract obstruction, infection, and fluid collections such as lymphocele. Acute rejection is characterized by tubulointerstitial and vascular lesions of varying severity. Acute tubulointerstitial rejection is characterized by interstitial edema, extravasation of erythrocytes, and infiltration of the intertstitium by a polymorphic infiltrate of mononuclear cells and a small number of polymorphonuclear leukocytes and eosinophils, resulting in varying degrees of tubular damage.13'15-17


Figure 8.17. (A) Renal transplantarteriogram 24 hours after transplant demonstrates patency of the anastomosis with very slow flow through the intrarenal branches, absence of opacification of peripheral arterial branches, and no opacification of the renal cortex (4 seconds

217

after injection). (B) Film 12 seconds after injection demonstrates a blotchy, nonhomogeneous nephrogram with absence of opacification of the renal cortex and persistence of contrast media in arterial branches (arrow). At the time of surgery, a necrotic kidney was found.

Acute vascular rejection is characterized in the mild form by subendothelial accumulations of mononuclear inflammatory cells and small aggregates of fibrin and platelets, with narrowing of the arterial lumen. These changes are progressive, with the development of areas of stenosis leading ultimately to vascular obstruction. Extensive fibrinoid necrosis of small arteries, arterioles, and glomerular capillaries is an important part of the process. In advanced chronic stages, there is fibrosis of the glomerular tufts and periglomerular areas. The vasculonecrotic process generally involves the whole thickness of the arteriolar walls, but it usually affects only the media and intima of the interlobular arteries.16'17 A more severe process includes transmural mononuclear inflammatory infiltrations, which are foci of necrotizing arteritis or fibrinoid necrosis. Thrombosis may occur in severe cases. Healing of the endothelial lesions results in varying degrees of fibrointimal thickening, whereas healing of the arteritis and fibrinoid necrosis produces changes similar to those seen in the healed stage of polyarteritis nodosa.18 The elastica is disrupted or fragmented, and the media is replaced by scar tissue. These changes may result in aneurysmal dilatation of the blood vessels.18-19

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Castaneda-Zuniga

In acute rejection, the earliest angiographic signs are a decrease of the arterial blood flow manifested by prolonged arterial washout time and enlargement of the kidney, with stretching of intrarenal arterial branches as a result of interstitial edema. There is poor cortical perfusion, manifested by poor filling of cortical vessels (fig. 8.18A), a nonuniform or striated cortical nephrogram, with an ill-defined corticomedullary junction and poor ornoopacification of veins (fig. 8.18B).6-14'20-27 Although simultaneous filling of arteries and veins may occur, it is a sign of redistribution of intrarenal blood flow that indicates severe cortical ischemia (fig. 8.19).14'27 The severity of these changes is related to the intensity of the rejection, the type of immunosuppressive therapy, and the stage at which the examination was performed.24

Figure 8.18. (A) Injection in right common iliac artery demonstrates patency of the anastomosis, very slow flow, marginal irregularities (arrows), and stretching of intrarenal arterial branches as a result of

interstitial edema. Note also the absence of opacification of peripheral intrarenal branches. (B) Film 6 seconds after injection demonstrates very slow flow, with faint opacification of the renal cortex.


Figure 8.19. Nephrographic phase of a renal transplant arteriogram demonstrates a nonuniform cortical nephrogram with

279

an ill-defined corticomedullary junction and simultaneous filling of arteries (arrows) and veins (v).

In chronic rejection, the angiographic findings reflect progressive obliteration of interlobar, interlobular, and arcuate arteries (fig. 8.20). These changes are usually not uniform throughout the kidney, with the most severe ones being seen in the interlobular arteries and lesser ones in the interlobar and arcuate vessels (fig. 8.21). The arterial washout time is normal or moderately prolonged and the nephrogram is patchy, reflecting areas of cortical infarction (fig. 8.22).6>1420-26 Foley et al. described a patient with

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Castaneda-Zuniga

Figure 8.20. (A) Renal transplant arteriogram demonstrates marginal irregularities of the main renal artery and of some seg mental branches (arrows}. Observe also

stretching of intrarenal arteries. (B) Film taken 10 seconds after injection demonstrates slow flow and absence of opacification of peripheral branches.


Figure 8.21. (A } Transplant arteriogram demonstrates extensive irregularities of

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the lobar and interlocutor arteries and pruning of peripheral branches.

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Castaneda-Zuniga

8.21. (B) Transplant arteriogram reveals occlusion (arrows), and pruning o extensive marginal irregularities (arrows), branches.


Figure 8.22. Nephrographic phase of renal transplant arteriogram demonstrates very slow flow with persistence of con-

223

trast medium in arterial branches with a nonhomogeneous patchy nephrogram throughout the entire kidney.

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Castaneda-Zuniga

chronic rejection who demonstrated fusiform aneurysms of the interlobar arteries on angiography.25 Saccular (fig. 8.23) and multiple, small, round, aneurysms of the interlobular arteries—closely resembling those of polyarteritis nodosa (fig. 8.24) —have been described by Castaneda-Zuniga et al. as an unusual manifestation of rejection vasculitis.19 Although no prospective study has been done, it has been reported that rejection is more frequent in kidneys undergoing angiography than in those that do not. It has also been said that an overwhelming number of the rejections in kidneys undergoing angiography start the day after the procedure.28 Differences in rejection frequency could not be explained by differences in human lymphocytic antigen matching or the origin of the kidneys. These findings suggest a possible connection, indicating that the angiography might elicit an acute rejection episode. A mechanism to start this rejection might be activation of the complement system that was found in 50% of the patients undergoing angiography in peripheral blood and in 100% when studied in vitro.28 Although these findings of a retrospective study were not verified by histology, acute episodes were diagnosed by the clinicians as rejections and treated as that. In four instances, the transplant was removed and histology showed rejection.28

Figure 8.23. (A) Donor arteriogram demonstrates a single renal artery with normal intrarenal branches, (fi) Allograft arteriogram reveals severe stensosis of one of the interlobar branches (arrow), with

a fusiform dilatation of the artery beyond the area of narrowing. (From CastanedaZuniga WR, et al.: Radiology 136:333335, 1980. Reprinted by permission.)


Figure 8.24. (A} Renal allograft ateriogram performed because of hypertension in patient with renal transplant demonstrates the presence of multiple small,

225

round aneurysms of the interlobular arteries (small arrows). Observe also a mild narrowing at the level of the anastomosis (open arrow).

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Castaneda-Zuniga

8.24. (B) Subtraction film of renal allograft arteriogram performed 3 years later because of persistence of hypertension demonstrates again the presence of multiple small, round aneurysms of inter-

lobular arteries (arrows). Observe the persistence of the stenosis of the main renal artery. (From Castaneda-Zuniga WR, et al.: Radiology 136:333-335, 1980. Reprinted by permission.)

Acute Tubular Necrosis With the use of kidneys from living related donors, acute tubular necrosis is now less frequently observed and is essentially restricted to patients receiving cadaveric allografts. Such factors as donor source, modality of harvesting and preserving the kidney, and operative technique influence the incidence of acute tubular necrosis, which ranges from 5 to 75%.1)2


227

When intraoperative biopsy does not show a rejection and oliguria or anuria develops immediately after surgery, acute tubular necrosis is clinically considered to be the most likely diagnosis. There is extensive controversy about the angiographic diagnosis of acute tubular necrosis, possibly because of differences in the severity of the disease or in the time of examination after onset of symptoms.24'29 Most commonly, acute tubular necrosis shows a normal or almost normal angiogram, but without excretion of contrast medium by the collecting systems (fig. 8.25), when the study is performed within 24 hours after the onset of acute tubular necrosis.6'24'26'29 However, when the angiogram is performed at a later time, pruning of intrarenal arteries may be present; in all cases, the vessels are smooth and regular, the capillary nephrogram is homogeneous, and there is delayed transit time manifested by late opacification of the renal vein and persistence of contrast medium in arterial branches (fig. 8.26).24>3° Similar changes have been described earlie as a manifestation of renal cortical ischemia.26'31 Renal papillary necrosis has been reported as a complicating factor in pyelonephritis and diabetes, ureteral obstruction, and other ischemic processes (fig. 8.27). In transplanted kidneys, it has been associated with widespread infection of the graft.32 Edmondson et al. reported papillary necrosis in a transplanted kidney and pointed out that rejection might underlie the papillary damage.33 In this case, papillary necrosis occurred as part of longterm rejection that led to gradual deterioration of the graft function. In one instance, acute, fatal papillary necrosis occurred 18 days after transplantation. In this case, angiography demonstrated a patent arterial anastomosis in the graft, with adequate filling of the interlobar arteries. However, the arcuate and interlobular arteries were not seen. It is conceivable that the papillary necrosis of the graft in this case resulted from a primary ischemic process related to the rejection phenomenon, as is suggested by the occlusion of these vessels demonstrated on histologic examination.34

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Castaneda-Zuniga

Figure 8.25. Renal allograft arteriogram reveals only slightly delayed flow through

the kidney and lack of excretion of contrast media by the collecting systems.


229

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Castaneda-Zuniga

Figure 8.26. Renal allograft arteriogram demonstrates slow flow and lack of opacification of peripheral branches at 2 seconds (A) and 7 seconds (B) after injection. (C) Film 9 seconds after injection

reveals a faint nephrogram with poor definition of the cortex, absent opacification of veins, and no excretion of contrast media by the collecting systems.


Figure 8.27. Renal angiogram reveals pruning of peripheral branches and displacement of arteries around dilated, de-

231

formed minor calices, with adjacent avascular areas probably representing necrotic papillae (arrows}.

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Castaneda-Zuniga

REFERENCES 1. Advisory Committee to the Renal Transplant Registry: The 12th Report of the Human Transplant Registry. JAMA 233:787-796, 1975. 2. Advisory Committee to the Renal Tranpslant Registry: The 13th Report of the Human Transplant Registry. Transplant Proc 9:9-26, 1977. 3. Goldman MM, Tilney NL, Vineyard GC, Laks H, Kahan MG, Wolson RE: Twenty year survey of arterial complications of renal transplantation. Surg Gynecol Obstet 141:758-760,1975. 4. Vidne BA, Leapman SB, Butt KM, Kountz SL: Vascular complications in human renal transplantation. Surgery 79:77-81, 1976. 5. Russo VR, Marks C: Renal transplantation: An analysis of operative complications. Ann Surg 42:153-159, 1976. 6. Boltuch Rl, Alfidi RJ: Selective renal angiography: Its value in renal transplantation. Urol Clin North Am 3:611-620, 1976. 7. Doyle TF, McGregor WR, Fox PS, Maddison FE, Rodgers RE, Kauffman HM: Homo-transplant renal artery stenosis. Surgery 77:53-59, 1975. 8. White Rl, Najarian J, Loken M, Amplatz K: Arteriovenous complications associated 409-411. 9. Kiser WS, Hewitt TD, Montie JE: Surgical complications of renal transplantation. Surg Clin North Am 51:1133-1140, 1971. 10. Fletcher EW: Selective phlebography of transplanted kidneys. Clin Radiol 21:144149, 1970. 11. Pool R: Angiographic aspects in kidney transplantation. Radiologia Clin 47:22-31, 1978. 12. Deal P, Hawkins IF: Venous collaterals in a human renal allograft. Radiology 106: 547-548, 1973. 13. Knudsen DF, Davidson AJ, Kountz, SL, et al.: Serial angiography in canine renal allografts. Transplantation 5:256-266, 1967. 14. Vinik M, Smellie WAB, Freed TA, Hume DM, Weidner WA: Angiographic evaluation of the human homotransplant kidney. Radiology 92:873-879, 1969. 15. Busch GJ, Galvanek EG, Reynolds ES, Jr: Human renal allografts. Analysis of lesions in long term survivors. Hum Pathol 2:253-298, 1971. 16. Busch GJ, Garovoy MR, Tilney NL: Variant forms of arteritis in human renal allografts. Transplant Proc 11:100-103, 1979. 17. Finkelstein FO, Siegel NJ, Bastl C, et al.: Kidney transplant biopsies in the diagnosis and management of acute rejection reactions. Kidney Int 10:171-178, 1976. 18. Meadows R, et al.: Renal histopathology: A Light. In: Electron and Immunofluorescent Microscopy Study of Renal Disease. London: Oxford University Press, 1978, pp. 409-411. 19. Castaneda-Zuniga WR, Sibley R, Zollikofer C, Nath PH, Valdez-Davila O, Colema C, Amplatz K: Renal artery aneurysms: An angiographic sign of transplant rejection. Radiology 136:333-335,1980. 20. Alfidi R, Meaney TF, Buonocore E, Nakamoto S: Evaluation of renal homotransplantation by selective angiography. Radiology 87:1099-1104,1966. 21. O'Connor JF, Dealy JB, Lindquist R, Couch NP: Arterial lesions due to rejection in human kidney allografts. Radiology 89:614-620,1967. 22. Staple TW, Chiang DTC: Arteriography following renal transplantation. Am J Roentgenol 10:669-680,1967. 23. Kaude JV, Hawkins IF: Angiography of renal transplant. Radiol Clin Am 16:295308,1976.


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24. Kause }, Slusher DH, Pfaff WW, Hackett RL: Angiographic diagnosis of rejection and tubular necrosis in human kidney allografts. ACTA Radiol (Diagn) 10:476-488, 1970. 25. Foley WD, Bookstein JJ, Tweist M, Giras PW, Taylor GH, Turcotte JG: Arteriography of renal transplants. Radiology 116:271-277, 1975. 26. Beachley MC, Pierce JD, Boykin JV, et al.: The angiographic evaluation of human renal allografts, Functional graft deterioration and hypertension. Arch Surg 111:134142, 1976. 27. Secky JW, Fletcher EWL: Renal homotransplant angiography. In Golden's Diagnostic Radiology. LI Robbins (Ed.). Baltimore: Williams & Wilkins, 1972, pp. 204-215. 28. Heideman M, Claes G, Nilson AE: The risk of renal allograft rejection following angiography. Transplantation 21:289-293, 1 976. 29. Gedgaudas E, White Rl, Loken MK: Radiology of renal transplantation. Radiol Clin North Am 10:529-544, 1972. 30. Becker JA, Kutcher R: The renal transplant: Rejection and acute tubular necrosis. Semin Roentgenol 13:352-362,1978. 31. Hollenberg NK, Epstein M, Rosen SM, Basch RJ, Oken DE, Merrill JP: Acute oliguric renal failure in man: Evidence for preferential renal cortical ischemia. Med 47: 455:474, 1968. 32. Knepshield JH, Feller A, Leb DE: Papillary necrosis due to Candida albicans in renal allograft. Arch Intern Med 122:441-444, 1968. 33. Edmondson RPS, Fawcett IW, Jones NF, et al.: Papillary necrosis in a transplanted kidney. Br Med J 1:547,1972. 34. Tuma S, Chaimowitz C, Erlik E, Gellei B, Rosenberger A, Better OS: Fatal papillary necrosis in a kidney graft. J A M A 235:754-755, 1976.

CHAPTER 9

Use of Ultrasonography Ruth Rosenblatt and Rosalyn Kutcher

Renal transplantation has become an accepted and often preferred treatment for the patient with chronic renal failure. Graft survival statistics reflect a slow but definite increase at 1, 3, and 5 years. With conventional immunosuppression, graft survival at 1 year still remains at 50-60% for cadaveric transplants.1 With the use of cyclosporin, however—a newer immunosuppressive agent—1-year survival of 72-80% has been reported.2-3 Graft failures tend to occur within the first 4 months following transplantation, and the majority of failures are due to rejection and acute tubular necrosis. Persistent though less common reasons for graft loss are urologic complications, vascular problems, infection, and primary graft nonfunction. The immediate posttransplantation period remains critical for monitoring renal allograft recipients. Recent refinements in ultrasonographic equipment have led to the inclusion of this imaging tool in the previously established armamentarium of diagnostic procedures—nuclear imaging, percu-

Use of Ultrasonography

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taneous biopsy, intravenous urography,angiography,and antegrade and retrograde pyelography. The chief advantage of ultrasonography is its ability to provide important anatomical information in a noninvasive manner independent of renal function. Further, the transplanted kidney lends itself to ultrasonographic examination: because it has a relatively superficial location, the sound beam is not hampered by gaseous or osseous interposition. An otpimal ultrasound image of the transplanted kidney provides excellent detail of gross renal anatomy, and renal axis can be determined quickly using dynamic or real-time scanning equipment. Routine baseline posttransplantation scanning can be performed as early as 24-48 hours following implantation. Significant ultrasonographic changes from the baseline study, when correlated with the clinical status and radionuclide studies, aid in the diagnosis and management of posttransplant complications.

ANATOMICAL AND TECHNICAL CONSIDERATIONS The standard surgical procedure of renal transplantation consists of removing the donor living or cadaver kidney, rotating it 180° from its native position so that its posterior surface faces anteriorly, and transplanting it extraperitoneally in the recipient's contralateral iliac fossa.4 An end-to-side anastomosis of renal artery to iliac artery and of renal vein to external iliac vein are usually performed. Urinary drainage is established by means of a ureteroneocystostomy of the donor ureter via a submucosal tunnel in the bladder (fig. 9.1). Individual anatomical variations of renal axis and anastomoses depend on host and donor factors. Several technical factors in the use of the ultrasound equipment are important in producing an optimal ultrasound image. The relatively superficial location of the transplanted kidney favors the use of a 3.5-5 MHz transducer frequency (somewhat higher than that used in conventional abdominal scanning) to obtain better near-field resolution. The transducer beam focusing profile must encompass the entire kidney thickness and perinephric space. In most ultrasound systems, the decibel output and depth gain curve are variables that need to be adjusted to optimize the image. The use of high-resolution dynamic or real-time equipment has the advantage of eliminating to a great extent the variables that are present in contact scanning and that are related to operator

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Rosenblatt and Kutcher

Figure 9.7. Diagrammatic representation of a transplanted kidney in the right iliac fossa. IVC, inferior vena cava; Ao, aorta; IA, iliac artery; RA, renal artery; RV, renal vein; K, kidney; U, ureter; B, bladder.

scanning technique. Dynamic scanning also has the advantage of demonstrating the renal axis quickly, depicting vascular pulsations, and enabling the operator to trace the caliceal complex to the renal pelvis and ureter, particularly if the latter is dilated. The field of view in certain real-time systems may not be wide enough to encompass the entire kidney. In such cases, a combination of real time as well as contact scanning results in a more complete examination. Since serial scanning of the transplanted kidney is the key to diagnosis of a number of complications, the scanning technique should be standardized and, whenever possible, the same equipment settings used ta minimize technical variables in producing the image. Care about technical details and reproducibility of the image renders the departure from baseline studies more meaningful. Sagittal sections of the transplanted kidney can be obtained after determining the renal axis in the iliac fossa. It may be helpful to record renal axis diagrammatically on the patient's chart or ultrasound record and thereby save time during subsequent studies (fig. 9.2). Transverse images 1-2 cm apart can be made at right angles to the sagittal axis. A standardized approach in imaging the transplanted kidney is particularly important if length, width, and anterior-posterior measurements are relied upon for volume calculations. The anterior-posterior dimension of the allograft is the most accurate measurement because it is in the axis of the ultrasound beam (fig. 9.3B). The perinephric area and the remainder of the renal pelvis, including the urinary bladder, are evaluated to search for abnormal fluid collections. On initial evaluation, the patient's native kidneys or nephrectomy site should be scanned so


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that the significance of subsequent abnormalities in those areas can be assessed.5 The ultrasound appearance of the transplanted allograft is similar to that of the normal kidney. Three zones of echo amplitude can be distinguished in the normal renal transplant (fig. 9.3A). These zones are arranged in a manner that reflects the gross anatomy of the kidney. Renal outline is ovoid and smooth. A compact area of high echogenicity can be seen in the center of the renal outline representing the connective tissue and fat of the renal sinus and pelvicaliceal system. Ovoid areas of decreased echogenicity around the renal sinus correspond to the pyramids. Surrounding and separating the pyramids is the renal cortex, which is normally more echogenic than the pyramids. Occasional high-amplitude reflections from the arcuate vessels can be seen at the periphery of the pyramids, thereby emphasizing the corticomedullary junction. The branching renal pelvis and proximal ureter may at times be recognized as an echo-free space when the collecting system is slightly distended during a period of diuresis or mild obstruction. Figure 9.2. Renal axis (A-B) shown in relationship to the external scar (C-D). Variations in renal axis and incisional scar are common.

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Figure 9.3. (A) Sagittal sonogram of a renal transplant obtained in a plane from patient's right hip to her left shoulder. Electronic calipers indicate pole-to-pole

distance or length. Note three zones of varying sonographic pattern: C, renal cortex; P, renal pyramid; and 5, renal sinus.


9.3. (B) Transverse sonogram of a renal transplant. Electronic calipers indicate distance between anterior and posterior surfaces or thickness. The transplant width can also be measured to provide,

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together with the length, three dimensions for volume determination. Note small fluid collection consistent with some rejection (arrow).

CLINICAL PROBLEMS Rejection Renal allograft rejection is one of the most common causes of posttransplant renal failure, occurring usually within the first 4-6 months of transplantation. Graft rejections may be classified as hyperacute, accelerated acute, acute, and chronic. 6 Both hyperacute and accelerated acute rejection, which are mediated by preformed humoral antibodies, may occur either atsurgery or (depending on antibody levels) within the first few days after transplantation. In this situation the kidney is not likely to be examined sonographically, but if the study is performed it may show a globular, hypoechogenic renal outline with no recognizable renal architecture. These findings presumably represent extensive infarction, hemorrhage, and edema.

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Acute rejection, which is mediated by antibodies produced by the T (thymic) lymphocytes, usually occurs after the first week following transplantation. Acute rejection is a dynamic process varying in severity that results in vascular compromise of small intrarenal arterioles, thus causing cortical ischemia with edema, mononuclear cellular infiltration, focal microhemorrhages, and infarction. Lesions may be focal or diffuse. Sonographic manifestations depend on the severity and extent of rejection. A spectrum of sonographic findings has been described in acute rejection (figs. 9.4 and 9.5)7"12 The most frequent observations have been increase in allograft volume, which is in large measure due to increase in size of renal pyramids; alteration in renal sinus echogenicity; and texture changes in cortical and medullary zones. A consistent but not specific finding is an overall increase in renal volume. Volumetric increase during rejection leads to a globular contour or focal lobulations of renal contour, and the change tends to be abrupt. By contrast, a gradual increase in size —taking place within the first month —has been observed in normal transplants.9 In a recent review of 50 biopsy-proven cases of acute rejection, Frick et al.7 found that increase in size and sonolucency of the renal pyramids occurred with a frequency of 88%. Presumably, these findings are a manifestation of edema. Objective assessment of the increase in volume of pyramids during rejection supports this observation.13 However, this finding alone is of limited value as a sign of rejection. Prominent pyramids may be seen in kidneys without rejection, and the patient's state of hydration has been shown to affect the size of the medullary pyramids.10 Nevertheless, in any given case, comparison with baseline study and observation of serial increase in size, together with clinical and laboratory data, are likely to be helpful in the diagnosis of rejection. Changes in the sonographic appearance of the renal sinus may also occur during rejection. A coarse, uneven distribution and sparcity of renal sinus echoes may be noted. Hricak et al.14 have correlated these changes with histopathologic observations of diminution of renal sinus fat and replacement by fibrous tissue. Patchy sonolucent zones in the renal cortex and medulla may coalesce and obliterate the corticomedullary junction (fig. 9.4). Focal areas of increased cortical echogenicity may also be noted (fig. 9.5B). Another feature frequently observed in rejection has been small, crescentic fluid collections around the transplanted kidney.10


Figure 9.4. Baseline sagittal scan of a renal transplant at 6 days (A ). On the 27th day, decreased renal output prompted repeat study (B). Note coalescence of

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pyramids in the anterior aspect of the kidney (white arrows) and sparcity of contiguous renal sinus echoes (open arrow).

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Figure 9.5. Sagittal sonogram of a transplanted kidney during early rejection at day 10 (A) and at day 25 (B). Patient has progressive increase in renal failure.

Note increased size of pyramids (arrows) and a cortical zone of increased echogenicity (open arrow).


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Chronic rejection is dependent on antibodies from the B lymphocyte system (similar to hyperacute rejection). Current experience in the sonographic findings of chronic rejection is limited. Hillman et al.8 have described a diminution in renal cortical thickness (presumably due to atrophy), with a coarse cortical texture and preservation of corticomedullary junction. Other investigators have observed changes in renal sinus echoes similar to those described in severe acute rejection. 15 The sonographic picture may be complicated by the coexistence of both acute and chronic rejection. Important limitations to the ultrasonographic evaluation of acute and chronic rejection should be noted. There is still a disparity between the sonographic and histologic findings and the observations of various investigators.14'15 Acute rejection may be present without any of the textural changes described above, particularly in mild or early cases. The departure from the normal renal ultrasound appearance is a qualitative change that is difficult to measure, and the interpretation is largely subjective. Many technical variables relating to the manner in which the ultrasound image is generated may produce spurious decrease or increase in echogenicity, leading to erroneous interpretation. The sonographic changes are therefore to be considered in context with the clinical status and radionuclide studies. More extensive application of high-resolution ultrasonographic equipment to the problems of acute rejection in renal transplantation should lead to further clarification of the textural changes seen in rejection. Acute Tubular Necrosis After transplantation, as many as 50% of cadaveric transplant recipients show evidence of acute tubular necrosis (ATM). 5 Several investigators studying ATM in the experimental models16 and in the clinical setting10'17 have noted the absence of sonographic textural changes in ATM in contrast to rejection. It has therefore been suggested that sonography may aid in distinguishing rejection from ATM when radionuclide studies are equivocal. More recently, Frick et al.7 noted increased size and decreased echogenicity of renal pyramids during episodes of acute tubular necrosis. One would expect that hydropic changes within tubules and interstitial edema occurring in ATM are lesions that may be depicted on highresolution sonographic scanning in the future. As in rejection, more collective experience is needed in the area of ultrasonographic tex-

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ture analysis to clarify present lack of specificity of sonographic findings.* The treatment of rejection involves administration of corticosteroids, whereas this therapy is contraindicated in ATM, infection, and other urologic complications. An erroneous decision to withhold or administer steroids may lead to graft loss and be hazardous to the patient. The clinical picture may be quite complex when classical signs and symptoms of rejection are not present and when radionuclide studies are equivocal. In addition, ATN and rejection may coexist. In a significant number of cases, percutaneous allograft biopsy using ultrasonographic guidance is being performed to make the diagnosis of rejection and influence the decision to initiate therapy. Although the role of ultrasound in the diagnosis of rejection and ATN is still in evolution, it has become an important screening tool in the diagnosis of the urologic complications described below. Urologic Complications Urologic complications are largely related to surgical technique of implantation. In addition, the renal allograft recipient is vulnerable to urinary tract infection and abscess formation as a result of immunosuppression and to possible anemia and uremia of renal failure. Fortunately, urologic complications in theposttransplantation period have decreased significantly from 10-21% in the early 1970s to less than 3% in recent years.8 Urologic complications are usually caused by perirenal fluid collections (which may be secondary to urinoma, lymphocele, hematoma, or abscess) and by ureteral or vascular obstruction. Such complications can be catastrophic if unrecognized or mistaken for rejection or ATN. Indeed, the clinical picture of decreased urine output, rising serum creatinine, enlarged tender kidney, and fever that occurs in rejection may be mimicked by the complications mentioned above. Because ultrasound is highly sensitive in delineating fluid, it has become the study of choice for the diagnosis of hydronephrosis and perinephric fluid collections.19"21

*The recent emergence of magnetic resonance imaging (MRI) is a promising aid in the study of the dynamic physiological and chemical changes occurring in rejection and ATN.


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Obstruction In the presence of obstruction, the ultrasound examination can demonstrate dilated calices that can be traced to a dilated renal pelvis and often to the ureter. The dilated collecting system produces splaying of the normally compact pelvicaliceal complex (fig. 9.6A). The diagnosis of obstruction should be made with caution. An overdistended urinary bladder may cause some compression of the distal ureter leading to mild hydronephrosis. For this reason, prevoiding and postvoiding scans should be obtained in equivocal cases. During a period of diuresis, mild dilatation of the collecting system may also be observed. In the immediate postoperative period, mild hydronephrosis may be noted; it is caused by edema at the ureterovesical junction, and it is reversible. Obstruction at the ureteroneocystostomy site may be related to vascular insufficiency secondary to transplantation technique or episodes of rejection, causing ischemia, necrosis, and subsequent fibrosis. Calculi, usually a late complication, may also obstruct the distal ureter. An infrequent cause of ureteral obstruction is ureteropelvic fibrosis. This has been a late complication, occurring between

Figure 9.6. Hydronephrosis. (A) Sagittal view of the transplanted kidney showing

dilated calices typical of hydronephrosis.

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9.6. (B) Antegrade pyelography performed with sonographic guidance demonstrates narrowing at the ureteroneocystostomy.

1 and 6 years following transplantation. This type of obstruction has produced caliectasis without significant dilatation of the renal pelvis (due to surrounding fibrosis).22 The sonographic appearance of ureteropelvic fibrosis may simulate renal papillary necrosis, also a late complication reported in some renal transplants.23 In renal papillary necrosis, papillary sloughing may create club-shaped caliceal spaces simulating caliectasis. In addition to intrinsic ureteral problems, extrinsic compression of the ureter may be caused by abnormal fluid collections.21 Although the ultrasound study provides the clue to the presence of hydronephrosis, opacification studies are needed to define the level of obstruction. Antegrade percutaneous pyelography can be performed using sonographic guidance (fig. 9.6B). Subsequent ureteral stenting and dilatation may maintain transplant function.


24 7

Fluid Collections Peritransplant fluid collections are common and may be seen in as many as 50% of renal transplant patients. A small amount of peritransplant fluid may be a concomitant finding during a rejection episode (fig. 9.3B). The significance of a peritransplant fluid collection depends on its size, location with regard to the collecting system, and progression. For this reason, serial scans can be extremely helpful (fig. 9.7).

Figure 9.7. Peritransplant fluid collection (arrow) seen in a transverse sonogram ( A ) baseline study in an asymptomatic

patient. The collection was presumed to represent a small hematoma.

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9.7. A follow-up scan 1 week later shows small residual mass (B).

The lymphocele, the most common extraurinary collection, is thought to occur as a result of division (without ligation) of lymphatics in the operative field or lymphatic leakage from the donor kidney. Lymphoceles tend to be well-demarcated, septated, sonolucent masses conforming in shape to the space they occupy (fig 9.8). These collections may occur after a period of rejection and usually weeks to months following transplantation. There may be associated leg edema, hydrocele, and scrotal edema.18Occasionally, an unrelated ovarian cyst may mimic a septated lymphocele (fig. 9.9).18 Vaughan et al. have suggested that pretransplant pelvic sonography be performed on female transplant recipients in an effort to avoid unnecessary diagnostic workupfollowingtransplantation.24 Urinomas usually form secondary to leakage at the ureteroneocystostomy site, and they tend to appear early in the posttransplant course. Their usual location is around the lower pole of the kidney and in close relationship to the urinary bladder. There is


Figure 9.8. Sagittal scan of a kidney 5 weeks after transplantation demonstrates a septated fluid collection (arrows). Per-

249

cutaneous aspiration confirmed the presence of a lymphocele.

often a decrease in urine output and increase in wound drainage. Although the ultrasound scan depicts the fluid, opacification studies such as excretory urography, retrograde pyelography, and radionuclide scanning are necessary to demonstrate presence of a leak and its site (fig. 9.10). An acutely enlarging hematoma is not likely to be studied sonographically because the diagnosis is usually clinically apparent with hypotension and drop in hematocrit, and emergency surgery is required. It is, therefore, the patient with a chronic hematoma who is studied sonographically because of decreased renal function, pain, or fever. As a hematoma undergoes organization with resorption of fluid and thrombus formation, it has a complex internal echo pattern (fig. 9.7). Superimposed infection of a preexisting fluid collection or a postoperative perirenal or pelvic abscess can be seen 1 week to several months after transplantation. The presence of debris within the abscess usually renders the collection more echogenic on ultrasound study.

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Figure 9.9. Pelvic fluid collection (M) in a woman with a renal transplant. The

fluid mass represents an ovarian cyst, KID, transplanted kidney; BL, bladder.

Sonographic specificity with regard to the type of fluid within a collection is poor. Percutaneous aspiration of fluid collections, however, can be performed under ultrasonographic guidance. Aspirations are usually diagnostic and sometimes may be therapeutic if the collection is large. In the case of lymphocele, surgical excision may be necessary to marsupialize this lesion, particularly when it recurs. Early discovery and treatment of a perinephric collection are important to avoid the possibility of obstruction and superimposed infection.


Figure 9.10. Urinoma. (A) Sonogram of the transplanted kidney 2 months following transplantation shows a perinephric fluid collection (open arrow). Patient

25 7

was readmitted with severe flank pain. Percutaneous aspiration demonstrated evidence of urine ascites.

Vascular Complications Renal artery obstruction or compromise is best studied angiographically, particularly since transluminal angioplasty can be attempted at the time of diagnosis. With increasing use of dynamic imaging or Doppler ultrasound technique, absence of arterial pulsations and flow are signs that may become helpful in the diagnosis of renal artery compromise. In a recent report by Berland et al.25 the use of pulsed Doppler analysis of the renal transplant was found to be sensitive enough to differentiate between arterial occlusion and severe rejection. Venous obstruction may lead to an edematous kidney with sonographic findings similar to those described for acute rejection.

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9.10. (B) Retrograde study shows the presence of a leak.

Other Problems The immunosuppressed renal transplant patient is susceptible to infection and abscess formation, which may affect the allograft or distant sites. We have observed abscesses in the native renal bed of a nephrectomized patient several years after nephrectomy. The diagnosis was established by percutaneous aspiration of the fluid


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collections after sonographic study. Local signs and symptoms of abscesses may be masked in this group of patients. The ultrasound study is an important tool (together with radionuclide scanning) in the detection and treatment of abscesses. One of the most dreaded complications of the immunosuppressed transplant recipient is overwhelming renal infection producing renal emphysema. 26 The presence of gas within renal parenchyma produces marked acoustic impedance mismatch, resulting in increased echogenicity, acoustic shadowing, and reverberation artifacts. Although the sonographic pattern should be suggestive of gas within the kidney, the computed tomography scan (even more than the plain film) is clearly diagnostic (fig. 9.11).

Figure 9.11. Renal emphysema. (A )Sonography of the transplanted kidney 6 weeks following implantation, and with 24-hour history of anuria. Note diffuse

echogenicity in the kidney (arrows) indicating the acoustical mismatch. No renal contour could be defined.

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9.11. A computed tomography scan of the flank (B) clearly demonstrates renal

emphysema (arrows).

An increased incidence of tumors in immunosuppressed patients has been well documented.6 The most frequent cancers are squamous cell carcinoma of skin and lymphoma.27 The high incidence of central nervous system lymphoma has been stressed in a recent report by Tubman et al.27 In this regard, computed tomography plays a major role in the diagnosis. In addition, extracranial lymphoma has been diagnosed with the aid of computed tomography as well as ultrasound.

SONOGRAPHY USED TO GUIDE NEEDLE OR CATHETER PLACEMENT Several diagnostic and some therapeutic procedures can be performed under sonographic guidance. Sonographic localization helps to choose the appropriate percutaneous site and to determine angle of approach and depth of target. When a biopsy is performed to confirm rejection, an optimal percutaneous site may be chosen to avoid the renal pedicle or a dilated collecting system. In the aspiration of perinephric fluid collections, the needle can be guided


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away from the kidney to diminish the likelihood of trauma. Ultrasound has also been used as a guide in the performance of diagnostic and therapeutic antegrade pyelography.

SUMMARY Prompt and accurate diagnosis of renal transplant complications is essential to decrease morbidity and mortality. The patient population in question is often in poor health and vulnerable to complications. Ultrasound, because of its noninvasive manner of study, plays an important role in early detection of problems in the posttransplant period. Judicious use and interpretation of the ultrasound study, together with close follow-up, is necessary to attain greater accuracy in the diagnosis of posttransplant complications and thereby to improve patient and graft survival.

REFERENCES 1. Williams GM: The kidney: Progress in clinical renal transplantation. Transplant Proc 11:4-10, 1979. 2. European Multicentre Study Group: Cyclosporin in cadaveric renal transplantation: One yearfollowup of a multicentre trial. Lancet 11:986-989, 1983. 3. Canadian Multicentre Transplant Study Group: A randomized clinical trial of cyclosporin in cadaveric renal transplantation. N Engl J Med 399:809-815, 1983. 4. Smith EH: Ultrasound and the evaluation of renal transplants. Post-graduate Radiology:! :3-24, 1981. 5. Kutcher R, Amodio JB, Rosenblatt R: Uremic renal cystic disease: Value of sonographic screening. Radiology 147:833-835, 1983. 6. Becker J A and Kutcher R: The renal transplant: Rejection and acute tubular necrosis. Semin Roentgenoi 13:352-562, 1978. 7. Frick MP, Feinberg SB, Sibley R, Idstrom ME: Ultrasound in acute renal transplant rejection. Radiology 138:657-660,1981. 8. Hillman BJ, Birnholz JC, Busch GJ: Correlation of echographic and histologic findings in suspected renal allograft rejection. Radiology 132:673-676, 1979. 9. Hricak H, Toledo-Pereyra LH, Eyler WR, et al.: The role of ultrasound in the diagnosis of kidney allograft rejection. Radiology 1 32:667-672, 1979. 10. Hricak H, Cruz C, Eyler WE, et al.: Acute post transplantation renal failure: Differential diagnosis by ultrasound. Radiology 139:441 -449,1981. 11. Maklad NF, Wright CH, Rosenthal SJ: Gray scale ultrasonic appearances of renal transplant rejection, Radiology 131:711 -717, 1979. 12. Bartrum RJ, Smith EH, D'Orsi CJ, et al.: Evaluation of renal transplants with ultrasound. Radiology 118:405-410, 1976.

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13. Fried AM, Woodring JH, Loh FK, Lucao BA, Kryscio RJ: The medullary pyramid index: An objective assessment of prominence in renal transplant rejection. Radiology 149:787-791,1983. 14. Hricak H, Romanski RN, Eyler WR: The renal sinus during allograft rejection: Sonographicand histopathologic findings. Radiology 142:693-699, 1982. 15. Gavelli G, Zompatori M: Echogenicity of the renal sinus during allograft rejection, (letters) Radiology 147:888-889, 1983. 16. Hricak H, Toledo-Pereyra LH, Eyler WR, et al.: Evaluation of acute-post transplant renal failure by ultrasound. Radiology 133:443-447, 1979. 17. Singh A, Cohen WN: Renal allograft rejection: Sonography and scontigraphy. Am J Roentgenol 135:73-77, 1980. 18. Becker JA, Kutcher R: Urologic complications of renal transplantation. Semin Roentgenol 13:341-351,1978. 19. Coyne SS, Walsh JW, Tisnado J: Surgically correctable renal transplant complications: An integrated clinical and radiologic approach. Am j Roentgenol 136:11131119,1981. 20. Morley P, Barnett E, Bell PRF, et al.: Ultrasound in the diagnosis of fluid collections following renal transplantation. Clin Radiol 26:199-207, 1975. 21. Silver TM, Campbell D, Wicks JD, et al.: Peritransplant fluid collections: Ultrasound evaluation and clinical significance. Radiology 1 38:145-151, 1981. 22. LaMasters DL, Katzberg RW, Confer DJ, Slaysman ML: Ureteropelvic fibrosis in renal transplants: Radiographic manifestations. Am J Roentgenol 135:79-82, 1980. 23. Koude J V, Stone M, Fuller TJ, Cade R, Tarront DG, Juncos LI: Papillary necrosis in kidney transplant patients. Radiology 120:69-74, 1976. 24. Vaughan R, Henderson SC, Rahatzad M, Barry J: Unsuspected adnexal masses in renal transplant recipients. J Urol 128:1017-1019, 1982. 25. Berland LL, Lawson TL, Adams MB, Melrose BL, Foley WD: Evaluation of renal transplants with pulse Doppler duplex sonography. Ultrasound Med Biol 1:215-222, 1982. 26. Brenbridge ANAG, Buschi AJ, Cochrane JA, Lees RF: Renal emphysema of the transplanted kidney: Sonographic appearance. Am J Roentgenol 132:656-658,1979. 27. Tubman DE, Frick MP, Hanto DW. Lymphoma after organ transplantation: Radiologic manifestations in the central nervous system, thorax, and abdomen. Radiology 149:625-631,1983.

CHAPTER 10

Evaluation by Digital Subtraction Angiography Antoinette S. Gomes

Digital subtraction angiography (DSA) is a form of digital radiography. In digital radiography, the X-ray signal is electronically detected, digitized, and processed before being displayed and stored. The technique allows detection of very low levels of iodinated contrast media such as those that occur in the arterial system following an intravenous injection of contrast.1"5 The X-ray imaging system used is a standard-image intensified fluoroscopy system with a wide dynamic-range TV camera. The video signal from the image intensifier is logarithmically enhanced and digitized on an image processor (computer). This signal, which is stored in one of two memories, serves as a mask. The mask is subtracted from digital images obtained after the injection of contrast media, and the subtraction images are stored on digital or analog disks or on magnetic tapes. Postprocedure reprocessingallows selection of different masks for subtraction, which is useful when patient motion has occurred.6 Hard copies can be obtained.

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Gomes

Commercially available DSA units are of two major types: those using analog data storage and those using digital storage. All digital units are superior because they offer the advantage of good dynamic range with little, if any, distortion and with preservation of good signal-to-noise ratio. Unlike analog systems, little or no noise is introduced with each analog to digital conversion of the image. DSA techniques permit imaging of the low-contrast levels produced after the intravenous injection of contrast media. Compared with conventional imaging methods, digital subtraction techniques offer improved contrast resolution at the expense of spatial resolution. In many circumstances, however, the fine detail obtainable with standard arteriography is not necessary to make correct diagnostic and therapeutic decisions.5 In these cases, DSA can eliminate the need for standard arteriography. When visualization of small vessels—such as intracranial cerebral vessels —is required, arteriography remains the procedure of choice. Diagnostic images of the aorta and renal arteries can be obtained with DSA.7'8 Average DSA techniques on a 14-in. mode image intensifier are 75 mA and 70 KvP per exposure; on the 6-in. mode they are 300 mA and 75 KvP. The exposures are similar to those for conventional angiography. DSA is useful in the evaluation of the renal transplant patient with recurrent hypertension. Following an apparent successful renal transplantation, hypertension occurs in about 25% of recipients. It may be secondary to renal artery stenosis, chronic rejection, ischemic damage to the graft at the time of surgery, ureteral obstruction, native kidney disease, steroids, or hypercalcemia. 9 Renal artery stenosis is reported to occur in 1-12%;10~12 but most series fall between these values,12"14 with the true incidence believed to approach 10%.9 Stenotic lesions have been reported to be one of two types.10'12'14 The more common is the short segment localized to the area of the anastomosis. The other type is a smooth tubular lesion involving only the donor artery.12 The clinical distinction between hypertension caused by rejection and by stenosis may be difficult. DSA is a useful means of evaluating the status of the renal artery in these cases (fig. 10.1). The procedure can be performed on an outpatient basis. A 5 or 6 French catheter is percutaneously placed in a large peripheral arm vein, or preferably is passed percutaneously via the basilic vein to the superior vena cava. One milligram of glucagon is administered intravenously to halt peristalsis. DSA images are severely

Digital Subtraction A ngiography

Figure 70.7. Digital intravenous subtraction angiographic study of a 13-year-old male after a cadaver transplant with one episode of rejection and later a hypertensive crisis. The study shows a high-grade stenosis at the site of the end-to-end

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anastomosis of the transplant to the right hypogastric artery (arrow}. The lesion was successfully dilated with a Gruntzig balloon catheter, leading to improvement in the patient's blood pressure.

degraded when motion has occurred between images undergoing subtraction. The patient is positioned in the steep ipsilateral oblique of the side of the renal transplant. A bolus injection of 35-40 cc of contrast media is injected intravenously at a rate of approximately 20 cc/second. Smaller volumes of contrast media are used in children. Intravenous DSA affords good visualization of the renal transplant artery anastomosis. Although visualization of interlobar arteries can be obtained, contrast enhancement of renal paren-

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chyma precludes adequate visualization of intrarenal vessels in most cases.15 Coupling of the DSA study with overhead films allows evaluation of the renal parenchyma, ureters, and bladder. A centrally placed catheter can also be used to obtain samples for renin sampling at time of DSA. The use of IV-DSA in the renal transplant patient is limited by the volume of contrast employed. Positioning of the patient in the correct obliquity for intravenous DSA is not precise because there is no opportunity for a "test" injection. As each injection is 35-40 cc, the number of injections that can be performed is limited. We have limited ourselves to two injections. Patients with markedly elevated levels of creatinine may be evaluated better with a selective arteriogram or arterial DSA that uses lowervolumes of contrast media. When DSA techniques are used in conjunction with selective or subselective arterial injections, the volume of the contrast media may be reduced by half or more of that needed for a regular arterial injection. Good visualization of vascular detail of large and small arteries is obtained with an arterial DSA study. New small-caliber, high-flow catheters can be used to perform arterial DSA studies on an outpatient basis. Intravenous DSA in combination with overhead films is potentially useful for the evaluation of renal donors. Large-field formats (such as 14-in. image intensifiers) are preferred here because smallfield image intensifiers may result in failure to detect accessory renal arteries.15 Additional studies are needed to determine the accuracy of DSA in determining the presence of these arteries. Intravenous or arterial DSA is also useful in follow-up of transplant patients after Gruntzig balloon dilatation. .Intravenous digital subtraction angiography is highly safe and has a good record of patient acceptance. Studies can be performed on a repeat basis when the risk and cost of conventional arteriography preclude serial follow-up studies, allowing valuable information to be obtained about the natural history of renal artery changes in the transplant patient. Efforts are presently directed at quantifying such physiologic functions as renal perfusion. Because DSA can be used with both arterial and intravenous injections of contrast, the angiographic study can be tailored to fit the individual needs of the patient.

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REFERENCES 1. Mistretta CA, Ort MG, Cameron JR, etal.: A multiple image subtraction technique for enhancing low contrast, periodic objects. Invest Radiol 8:43-49, 1973. 2. Nudelman S, Capp MP, Fisher HD III, etal.: Photoelectronic imaging for diagnostic radiology and the digital computer. Proc Soc Photo-Optical Inst Eng 164:138-146, 1978. 3. Kruger RA, Mistretta CA, Lancaster J, et a!.: A digital video image processor for real time X-ray subtraction imaging. Opt Eng 17:652-657, 1978. 4. Ovitt TW, Capp MP, Christenson P, et al.: Development of a digital video subtraction system for intravenous angiography. Proc Soc Photo-Optical Inst Eng 206:73-76,1979. 5. Mistretta CA, Crummy AB, Strother CM: Digital angiography: A perspective. Radiology 139:273-227, 1981. 6. Mistretta CA, Kruger RA, Ergun DL, et al.: Digital vascular imaging. Philips Medical Systems, Inc. Monogr, Shelton, Conn., n.d. 7. Buonocore E, Meany TF, Borkowski GP, Pavlicek W, Gallagher J; Digital subtraction angiography of the abdominal aorta and renal arteries. Comparison with conventional aortography. Radiology 139:281-286,1981. 8. Hillman BK, Ovitt TW, Nudelman S, Fisher HD III, et al.: Digital video subtraction angiography of renal vascular abnormalities. Radiology 1 39:277-280,1 981. 9. Smith RB, Ehrlich RM: The surgical complications of renal transplantation. Urol Clin North Am 3:621-646, 1976. 10. Margulis RM, Belzer FO, Kountz SL: Surgical correction of renovascular hypertension following allotransplantation. Arch Surg 106:1 3-1 6, 1973. 11. Doyle TF, McGregor WR, Fox PS, et al.: Homo-transplant renal artery stenosis. Surgery 77:53-60,1975. 12. Morris PJ, Yadav RV, Kincaid-Smith P, et al.: Renal artery stenosis in renal transplantation. Med J Aust 1:1225-1257, 1971. 13. Nerstrom B, Ladefoged J, Lund FL: Vascular complication in 155 consecutive kidney transplantations. Scand J Urol Nephrol 6 (Suppl): 65-74, 1972. 14. Smellie WA, Vinick M, Hume DM: Angiographic investigation of hypertension complicating human renal transplantation. Surg Gynecol Obstet 128:963-968, 1969. 15. Smith CW, Winfield AC, Price RR, et al.: Work in progress: Evaluation of digital venous angiography for the diagnosis of renovascular hypertension. Radiology 144: 51-54, 1982.


PART

Ill

Therapeutic Techniques


CHAPTER 1 1

Interventional Radiology in the Management of Complications W. R. Castaneda-Zuniga, David W. Hunter, and Kurt Amplatz

In recent years, new invasive radiologic procedures are making significant contributions to the management of patients with chronic renal insufficiency in hemodialysis and after renal transplantation. Among these techniques are transluminal angioplasty of stenotic arteriovenous shunts and fistulas for hemodialysis; transluminal angioplasty of transplant renal artery stensis; percutaneous antegrade nephrostogram and percutaneous nephrostomy drainage; and therapeutic embolization of large arteriovenous fistulas after native nephrectomy. Percutaneous biopsy has long been accepted as a routine procedure in the diagnostic evaluation of the patient with parenchymal complications of renal transplantation. The techniques that we are describing here, even though they are less invasive than a biopsy, have only recently been accepted as part of the diagnostic and therapeutic management of these patients.

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TRANSLUMINAL ANGIOPLASTY OF ARTERIOVENOUS FISTULAS FOR CHRONIC HEMODIALYSIS The creation of a subcutaneous arteriovenous fistula is the preferred method for maintaining vascular access for chronic hemodialysis. Venous angiography can clearly demonstrate the anatomy of the arteriovenous fistulas.1'2 As the fistula develops, the involved vessels become larger, primarily the anastomotic vein and, to a lesser degree, other veins in the same extremity. The anastomosis between the artery and vein does not normally increase in size because it is usually constructed with a nonabsorbable suture materi-

Figure 7 7 . 7 . (A) Fistulogram reveals a long segment of narrowing (white arrows) of efferent vein, just distal to the anastomosis with radial artery (black arrow}.

Interventional Management of Complications

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a). This lack of increase should not be confused with an area of narrowing. The fistulogram may demonstrate a stenosis, usually in the efferent venous channel just distal to the anastomosis (fig. 11.1 A); however, venous stenosis of the efferent limb can be found in places remote from the anastomosis (fig. 11.2A).3'4 Venous stenosis can result from weakening of the vein wall due to the trauma of repeated needle punctures, from angulation due to tortuosity of the vessels, and from intimal proliferation or perivenous fibrosis due to repeated needle punctures and perivascular bleeding. Trauma caused by tourniquet application can cause stenoses of the venous limb far from the site of puncture (fig. 11.2A). Stenosis of the arterial limb can occur as a result of trauma at the time of original surgery or of stretching of vessels to create the anastomosis.

77.7. (B) Wide guide wire passed across stenosis.

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7 7.7. (C) Postdilataion fistulogram reveals normal caliber at dilated segment.


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11.1. (D) Gruntzig balloon inflated at site of narrowing. Note the typical hourglass deformity (arrow}.

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7 7 . 7 . (£") Almost complete disappearance of deformity on balloon.


Figure 77.2. (A) Fistulogram on failing arteriovenous fistula reveals complete occlusion of cephalic vein just above the elbow (arrows).

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77.2. (B) Postdilatation fistulogram with guide wire (0.026 in.) in place.


77.2. (C) Fistulogram after removal of guide wire and performance of pressure measurements reveals normal lumen size at site of recanalization.

2 73

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77.2. (D) Fistulogram injecting in the radial artery, after demonstration of a severe pressure gradient across the fistula, reveals a stenosis of the distal radial artery (arrow).


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11.2. (E) Postdilatation fistulogram reveals normal caliber of dilated site.

Until recently, the presence of a severe narrowing or occlusion of either the artery (fig. 11.3) or the vein (fig. 11.2A) required a surgical revision of the fistula. Since the introduction of transluminal angioplasty, however, several investigators have demonstrated that localized areas of stenosis can be easily managed by balloon dilatation.3"9 Extensive areas of venous narrowing or occlusion have been said to be difficult to dilate and to require surgical repair with the interposition of a vascular graft.2 This has not been the case in our experience (figs. 11.1-11.3).

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Figure 77.3. (A) Fistulogram injecting through the distal radial artery beyond the fistula reveals complete occlusion at level of fistula (arrows). Catheter is placed in a retrograde fashion on proximal vein (small arrows).


77.3. (B) After gentle probing with a guide wire, the occluded segment was successfully recanalized and dilated with Teflon dilators (arrows] and a Gruntzig balloon.

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77.3. (C) Postdilatation fistulogram reveals a patent efferent vein.

The results of transluminal angioplasty of arteriovenous fistulas have not been as favorable as those for atherosclerotic arterial lesions.3"9 In our short experience, we have been able to provide adequate relief of the obstruction in all of the cases by using a variety of Teflon dilators, followed by Gruntzig nonexpandable balloons. Method The puncture is done approximately 1-3 cm distal to the site of maximum intensity of the bruit. A tourniquet placed proximal to the fistula to prevent venous return helps to ensure maximum venous distension for the puncture and occasionally permits visuali-


279

zation of the distal vein, which further simplifies the puncture. A fistulogram is performed using cinefluoroscopic equipment with video or other playback capability. A blood pressure cuff is placed around the upper arm to produce arterial occlusion, resulting in opacification of both arterial and venous limbs of the fistula (fig. 11.1 A). Angulated projections can be used to separate overlapping vascular structures. The venous anatomy from the fistula up the arm to the axillary and subclavian veins can be demonstrated by releasing the tourniquet and either following the flow of contrast medium with the C-Arm through the different areas or shifting the tabletop to the area of interest. If this technique does not permit a good evaluation of the proximal anatomy, a second injection is performed without a tourniquet to allow the flow of contrast medium to be followed through the different areas. Once the site of vascular narrowing is demonstrated, 5,000-6,000 units of heparin are administered through the catheter. Pressure measurements are performed through the angiographic catheter, with the holes of the catheter located in the vein proximal to the area of stenosis. This measurement should be equal to the systemic blood pressure as measured with a blood pressure cuff on the opposite arm. If it is not, a more proximal stenosis may be present, such as at the anastomotic site (fig. 11.2D). In one of our patients, recanalization and dilatation of a completely occluded segment of the efferent vein (fig. 11.2A-C) did not improve the pressure gradient or flow through the fistula. Stenosis at the anastomosis and in the distal segment of the radial artery (fig. 11.2D and E) had been obscured by the more obvious venous obstruction (fig. 11.2A). Without pressure measurements, such a case would undoubtedly have yielded an unsatisfactory result. The low pressure in the venous limb would have led to a low return rate during hemodialysis, and possibly to thrombosis. Once the pressure has been measured, a guide wire is passed across the obstruction and advanced proximally in the vessel (fig. 11.IB). Over this guide wire, Teflon dilators up to an 8 French size are passed in succession while being careful to keep the guide wire in place. After the 8 French dilator, a Gruntzig 6 mm- or 8-mm balloon is passed and inflated at the site of vascular narrowing. Multiple inflations, each 1 minute in duration, are performed at a pressure of 4-6 atmospheres until the deformity in the balloon disappears completely (fig. 11.1 D and E). The 0.038-in. guide wire is then replaced by a fine 0.018 or 0.022 guide wire, and the cath-

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eter is withdrawn to a point proximal to the site of dilatation. With the wire still in place, a small amount of contrast medium is injected to visualize the site of dilatation (fig. 11.28). If it seems to be wide open, the guide wire is removed and a fistulogram is performed (figs. 11.1C, 11.2C, and 11.3C). Close cooperation with the vascular or transplant surgeon is of maximum importance for successful results. When the artery or vein is completely obstructed, gentle probing with a floppy-tipped guide wire or a tight J guide wire usually permits passage across the occluded segment (fig. 11.3). This probing is followed by the usual dilatation procedure.

TRANSLUMINAL ANGIOPLASTY OF TRANSPLANTED RENAL ARTERIES Hypertension secondary to a stenosis of the transplanted renal artery occurs with an incidence varying from 1 to 12%.10"14 It can be a result of the surgical procedure (clamp injury, intimal flap following endarterectomy, or fibrosis at the suture line); a rejection episode; an atheromatous lesion of the aorta or iliac vessels; or extrinsic compression by a pelvic mass (fluid collection, tumor, edematous kidney, etc.). Angiography plays a major role in the evaluation of these problems and in their differentiation from graft rejection. Traditionally, transplant renal artery stenosis has been managed surgically with fair results. Transluminal angioplasty, which has been used successfully in the management of peripheral vascular disease, has recently been extended to the treatment of renal artery stenosis.15'16 Transluminal angioplasty is an accepted procedure in the management of nontransplant patients with hypertension secondary to renal artery stenosis caused by atherosclerotic lesions or fibromuscular dysplasia. The success rate varies from 95% in patients with fibromuscular dysplasia to 70% in patients with unilateral atherosclerotic lesions in whom a renin-dependent hypertension has been documented.17'18 Very recently, the procedure has also been successfully applied to patients with stenosis of the transplanted renal artery.19 The stenotic lesion in the transplant renal artery is most often at or just beyond the site of anastomosis. Vascular narrowings have also been demonstrated in the aorta or iliac artery proximal to the anastomosis.


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Method When renovascular hypertension is suspected in a transplant patient, an angiogram must be performed to demonstrate the presence of arterial narrowing. If the end-to-end anastomosis is between the recipient's hypogastric artery and the donor's renal artery, the approach should be from the contralateral femoral artery or from the left axillary artery (fig. 11.4). In these patients, the selective

Figure 11.4. (A) Stenosis, end-to-end anastomosis of transplanted renal artery

to stump of hypogastric artery (arrows).

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7 7.4. (B) Postdilatation angiogram reveals increase in lumen size at dilatation site

(arrows).

advancement of a catheter into the renal artery beyond the site of arterial narrowing is more easily accomplished from the axillary approach. In the patient with an end-to-side anastomosis—between the end of the donor's renal artery and the side of the recipient's iliac artery—the approach is through the ipsilateral femoral artery (fig. 11.5). A Gruntzig balloon of a size appropriate to the size of the transplant renal artery (commonly between 5 and 6 mm) is selected. Prior to dilatation, pressure measurements across the stenosis should be performed if possible. If the stenosis is too severe, the catheter will occlude the lumen and be inaccurate. Before the


283

Gruntzig balloon catheter is placed across the stenosis, 5,0006,000 units of heparin are given intravenously. Balloon inflations are performed at a pressure of 5-6 atmospheres until the deformity in the balloon disappears. Pressure measurements can then be performed with the Gruntzig balloon or, for greater accuracy, with a 5 French catheter. If the gradient is less than 20 mm Hg, the pro-

Figure 11.5. (A) Stenosis of both segmental renal arteries in an end-to-side

anastomosis (arrows).

254


77.5. (B) Postdilatation angiogram reveals increase in lumen size at dilatation sites

in both renal arteries (arrows).

cedure is terminated and a postangioplasty angiogram is performed (figs. 11AB and 11.56). If the pressure gradient is greater than 20 mm Hg, the same balloon or a larger one is replaced and further dilatations are performed until adequate relief of the stenosis, as demonstrated by pressure measurements, is obtained


285

PERCUTANEOUS ANTEGRADE NEPHROSTOGRAM AND PERCUTANEOUS NEPHROSTOMIES Improvements in surgical, diagnostic, and immunologic techniques in recent years have decreased the frequency of the urologic complications from 10-13% to 1-3%.20>21 Urologic complications can be divided into those that occur early (less than 3 months) or late (greater than 3 months) after transplantation. The early complications are either urine leaks or obstruction; extravasation of urine may or may not be associated with obstruction. Extravasation without obstruction (fig. 11.6) is seen in the following situations: a leak at the anastomotic site secondary to a faulty anastomosis; a leak at the anastomosis secondary to ureteral ischemia with necrosis of the distal ureter; a leak from the bladder secondary to faulty closure of the cystotomy; and a leak from the transplant pelvis or proximal ureter secondary to rejection or ischemia with resultant necrosis.22"28 Extravasation of urine can be secondary to obstruction,23"24 and the collection of extravasated urine may further increase the degree of obstruction. The primary diagnostic procedure in the evaluation of urine leaks has been the intravenous pyelogram. Its limitations, however, are significant. Urine extravasation can be proven by radionuclide studies long before it is demonstrated by the contrast pyelogram.24"31 Cystography more accurately demonstrates extravasation at the ureteroneocystostomy or cystotomy. If renal function is poor, a retrograde pyelogram more clearly demonstrates the extravasation from the ureter or renal pelvis. However, the selective catheterization of the newly created ureteral meatus is not easy, and not infrequently it is unsuccessful. In these cases, an antegrade nephrostogram via a direct puncture of the renal pelvis is indicated. The most common late urologic complication is obstruction, which usually occurs at the ureterovesical junction but can occur at any point along the ureter. Many causes of obstruction have been found including kinks; fibrosis following inflammation, rejection, or ischemia; lymphocele (fig. 11.7); tumors; and an edematous transplant.32"36 Less commonly, obstruction can be secondary to a calculus or clot.37 Because morbidity and mortality increase when treatment is delayed, accurate and rapid diagnosis is of great importance. Often, however, it is difficult to distinguish between rejection and urinary

286


Figure 71,6. Posttransplantation leak. Percutaneous antegrade pyelogram with Chiba needle reveals extravasation of

contrast medium (arrows), despite the presence of a ureteral catheter (small arrows).


Figure 11.7. Percutaneous nephrostogram after placement of drainage catheter reveals severe narrowing of distal ureter

28 7

(arrows) in patient with extrinsic compression by large lymphocele.

obstruction in a patient presenting with deteriorating renal function. The intravenous pyelogram has only limited value. In the presence of poor renal function, a renogram can frequently help to establish a diagnosis of rejection. Ultrasound and renograms can show obstruction, but usually not its exact nature.22'38'39 Percutaneous antegrade techniques appear to be the only way to make a definite diagnosis of obstruction and to distinguish between functional and fixed types (fig. 11 .g).21'36'40"44 When a diagnosis of obstructive uropathy is established, a temporary nephrostomy drainage can be performed to decompress the collecting systems and allow renal function to stabilize. The resulting levels of creatinine and urea should reflect the true state

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Castaneda-Zuniga, Hunter, and Amp/atz

Figure 11.8. (A ) Percutaneous nephrostogram reveals marked hydronephrosis. Note narrowing of distal ureter. Guide wire is placed across the ureteroneocystostomy into the bladder at an angle of

90° between distal ureter and wire in bladder, which is almost empty. Inflated balloon of Foley catheter (arrows) is shown.


77.5. (B) After bladder is half-filled, the angle between the intramural portion of the ureter and the bladder narrows, as

289

demonstrated by a smaller angle in the wire (45°).

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Castaneda-Zi/niga, Hunter, and A mplatz

11.8. (C) With the bladder fully distended, the angle has diminished to about 20°.

of the renal parenchyma. When renal function has become stable, the obstruction can be surgically corrected. Method Percutaneous puncture of the renal pelvis is best accomplished under ultrasound guidance. If kidney function is adequate, the renal pelvis can be opacified by the intravenous administration of contrast medium. As a general rule, the puncture should be performed from the lateral surface of the kidney, to allow a long


Figure 11.9. Diagram of puncture in patient with renal transplant to avoid the

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vascular pedicle.

needle tract through the renal parenchyma and to prevent injury to the vascular structures in the renal hilum (fig. 11.9). If a nephrostogram is all that is required, the puncture is done with a Chiba needle, and enough contrast medium is injected to opacify the collecting system up to the site of the obstruction. Functional tests (such as the Whitaker test) can be performed at this point.42'45'46 If temporary drainage is needed, the tract is dilated up to 7 or 8 French with Teflon dilators and a nephrostomy drainage catheter is placed. If the obstruction can be negotiated with a guide wire, the tip of the drainage catheter can be placed in the urinary bladder to allow internal drainage. A future possibility in some of these lesions, especially those with narrowing at the site of the ureterovesical anastomosis, is balloon dilatation with a Gruntzig catheter. The technique may permit this high-risk group of patients to avoid surgery.

292


THERAPEUTIC EMBOLIZATION OF LARGE ARTERIOVENOUS FISTULAS Renal arteriovenous fistula caused by nephrectomy of the native kidneys is a rare complication that may develop over a period of time ranging from days to years.47'48 Because of its large size, the fistula causes high output failure with or without cardiac decompensation.49-50 Simultaneous ligation of the renal artery and vein has been incriminated as the main causative factor in a high percentage of cases.47"50 Fistulas with hemodynamic disturbances that are causing symptoms have to be surgically corrected. Nonoperative occlusion of arteriovenous fistulas can be performed by using a barbed spring embolus (figs. 11.10 and 11.11 )50 or stainless steel spider (fig. 11.12) to form a baffle over which additional embolic material—commonly spring coils—are deposited to obtain complete obliteration.51 Particulate material should not be used because it can pass through the baffle and embolize to the lungs.

Figure 77.10. (Left) Injection on stump of renal artery (arrows) reveals massive shunting into the stump of the renal vein (large arrows). A large vascular space connects both vessels. (Right) Postembolization aortogram reveals obliteration of

the fistula with spring coils. (From Castaneda-Zuniga WR, et al.: JAMA 236:2649-2650, 1976. Copyright 1976, American Medical Association. Reprinted by permission.)

Interventlonal Management of Complications

Figure 7 7 . 7 7 . Modified spring embolus with barbs.

Figure 77.72. Stainless steel spider.

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Method The stump of the renal artery is selectively catheterized with a 9 French Teflon catheter. A preembolization angiogram is obtained by injecting 40 cc of contrast medium at 20 cc/second to demonstrate the anatomy and to measure accurately the size of the vessel. The barbs of the spring embolus or the legs of the spider are then sized to the caliber of the vessel. If a barbed spring embolus is to be used, it is loaded in the catheter with the barbed end ahead and pushed with a regular 0.038in. guide wire. As soon as the barbs protrude from the tip of the catheter, they become embedded in the wall of the artery and the spring coil forms a baffle in the lumen of the vessel, allowing additional embolic material to be delivered safely. If a spider or a spider with compressed ivalon plug is used, the legs of the spider have to be introduced first to ensure their fixation on the vessel wall. Once the spider is in place, additional embolic material can be introduced (fig. 11.13).


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Figure 77.73. (A) Large arteriovenous fistula between stump of renal artery and vein. (B) Film after placement of two spiders to prevent migration of emboli. (C) Film after placement of twospring emboli on top of the two spiders to complete the obliteration.

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REFERENCES 1. Anderson CB, Gilula LA, Harter HR, Etheredge EE: Venous angiography and the surgical management of subcutaneous hemodialysis fistulas. Ann Surg 187:194-204, 1978. 2. Glanz S, Bashist B, Gordon DH, Butt K, Adamson R: Angiography of upper extremity access fistulas for dialysis. A J R 143:45-52, 1982. 3. Gordon DH, Glanz S: Balloon dilatation of arteriovenous shunts in the chronically hemodialyzed patient. In: Transluminal Angioplasty. WR Castaneda (Ed.). New York: Thieme Stratton, 1982. 4. Gordon DH, Glanz S, Butt KM, Adamson RJ, Doening MA: Treatment of stenotic lesions in dialysis access fistulas and shunts by transluminal angioplasty. A J R 143: 53-58,1982. 5. Heidler R, Zeitler E, Gessler V: Percutaneous transluminal dilatation of stenosis behind A-V fistulas in hemodialysis patients. In: Percutaneous Vascular Recanalization. New York: Springer-Verlag, 1978, pp. 142-144. 6. Martin EC, Diamond NG, Casarella WJ: Percutaneous transluminal angioplasty in nonatherosclerotic disease. Radiology 135:27-33,1980. 7. Kalman PG, Hobbs BB, Colapinto RF, et at.: Percutaneous transluminal dilatation of a stenotic arteriovenous bovine graft. Dial Transplant 9:777-778, 1980. 8. Novelline RA: Percutaneous transluminal angioplasty: Newer applications. AJR 135:983-988,1980. 9. Lawrence PF, Miller FJ, Mineau DE: Balloon catheter dilatation in patients with failing arteriovenous fistulas. Surgery 89:439-442, 1981. 10. Goldman MN, Tilney NL, Vineyard GC, Laks H, Kahan MG, Wolson RE: Twenty year survey of arterial complications of renal transplantation. Surg Gynecol Obstet 141:758-760,1975. 11. Vidne BA, Leapman SB, Kountz SL: Vascular complications in human renal transplantation. Surgery 79:77-81, 1976. 12. Russo VR, Marks C: Renal transplantation: An analysis of operative complications. Ann Surg 42:153-159, 1976. 13. Boltuch Rl, Alfidi RJ: Selective renal angiography: Its value in renal transplantation. Urol Clinic North Am 3:611-620, 1976. 14. Doyle TF, McGregor WR, Fox PS, Madison FE, Rodgers RD, Kauffman HM: Homotransplant renal artery stenosis. Surgery 77:53-59, 1977. 15. Schwarten DE, Yune HY, Klatte EC, Grim CE, Weinberger MH: Clinical experience with percutaneous transluminal angioplasty (PTA) of stenotic renal arteries. Radiology 135:601-604, 1980. 16. Tegtmeyer CJ, Dyer R, Teates CD, Ayers CR, Carey RM, Wellons HA, Stanton LW: Percutaneous transluminal dilatation of the renal arteries: Techniques and results. Radiology 1 35:589-600,1980. 17. Sos T: Late follow-up of results of renal angioplasty. Presented at the Cardiovascular Radiology Annual Meeting, Palm Springs, Cal.: Feb 1982. 18. Tegtmeyer CJ, Teates CD, Crigler N, Gandee RW, Ayers CR, Stoddard M, Wellons HA: Percutaneous transluminal angioplasty in patients with renal artery stenosis: Follow-up study. Radiology 140:323-330, 1981. 19. Saddenkni S, Sniderman KW, Hilton S, Sos T: Percutaneous transluminal angioplasty of nonatherosclerotic lesions. AJ R 1 35:975-982,1980. 20. Salvatierra O, Olcott C, Amend WJ, Cochrum KC, Feduska NJ: Urological complications of renal transplantation can be prevented or controlled. J Urol 117:421427,1977.


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21. Becker JA, Kutcher R: Urologic complications of renal transplantation. Semin Roentgenol 13:341-351,1978. 22. Fletcher EWL, Lecky JW: The radiological demonstration of urological complications in renal transplantation. Br J Radiol 42:886-891,1969. 23. Malek GH, Uehling DT, Daouk AA, et al.: Urological complications of renal transplantation. J Urol 109:173-176, 1973. 24. Marx WL, Halasz NA, McLaughlin AP, et al.: Urological complications in renal transplantation. J Urol 11 2:561 -563, 1 974. 25. Colfry AJ Jr, Schlegel JU, Lindsey ES, et al.: Urologic complications in renal transplantation. J Urol 112:564-566, 1974. 26. Barry JM, Larson RK, Strong D, et al.: Urologic complications in 173 kidney transplants. J Urol 11 2:567-571, 1974. 27. Ehrlich RM (Ed.): Renal transplantation: Surgical aspects, part II. Urology 10 (Suppl 1), 1977. 28. Cook GT, Cant JD, Crassweller PO, et al.: Urinary fistulas after renal transplantation. J Urol 118:20-21, 1977. 29. Blahd WH: Nuclear Medicine (3d ed.). New York: McGraw-Hill, 1971. 30. Salvatierra O Jr, Olcott C IV, Amend WJ Jr, et al.: Urological complications of renal transplantation can be prevented or controlled. J Urol 11 7:421 -424,1977. 31. Texter JH, Haden H: Scintiphotography in the early diagnosis following renal transplantation. J Urol 116:547-549, 1976. 32. Ehrlich R, Smith R: Surgical complications of renal transplantation. Urology 10 (Suppl): 43-56, 1977. 33. Mehta SN, Kennedy JA, Loughridge WGG, Douglas JF, Donaldson RA, McGoewn MG: Urological complications in 119 consecutive renal transplants. Br J Urol 51:1 84, 1979. 34. LaMasters DL, Katzberg RW, Confer DJ.etal.: Ureteropelvic fibrosis in renal transplants: Radiographic manifestations. AJR 135:79-82, 1980. 35. Palmer JM, Chatterjee SN: Urologic complications in renal transplantation. Surg Clin North Am 58:305-317,1978. 36. Turner AG, Hewlett KA, Eban R, Williams GB: The role of antegrade pyelography in the transplant kidney. J Urol 123:812-814, 1980. 37. Leapman SB, Vidne BA, Butt KM, et al.: Nephrolithiasis and nephrocalcinosis after renal transplantation: A case report and review of the literature. J Urol 115:129-132, 1976. 38. Imray TJ, Gedgaudas E: Excretory urography in the evaluation of renal transplants. Radiology 95:653-656, 1970. 39. Koehler PR, Kanemoto HH, Maxwell JG: Ultrasonic "B" scanning in the diagnosis of complications in renal transplant patients. Radiology 119:661-664, 1976. 40. Barbaric ZL, Thompson KR: Percutaneous nephropyelostomy in the management of obstructed renal transplants. Radiology 126:639-642, 1978. 41. Coyne SS, Walsh JW, Tisnade J, et al.: Surgically correctable renal transplant complications: An integrated clinical and radiologic approach. AJR 1 36:1113-1119,1981 42. Shiff M, Rosenfield AT, McGuire EJ: The use of percutaneous antegrade renal perfusion in kidney transplant recipients. J Urol 122:246-248,1979. 43. Whitaker R: An evaluation of 120 diagnostic pressure flow studies of the upper urinary tract. J Urol 121:602-607,1979. 44. Mayo M, Ansell J: The effect of bladder function on the dynamics of the ureterovesical junction. J Urol 123:229-231, 1980. 45. Marshal S, Guthrie T, Jeffs R, Politano V, Lyon RP: Ureterovesicoplasty: Selection of patients. Incidence and avoidance of complications, a review of 3,527 cases. J Urol 118:829-831,1977.

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46. Hunter DW, Castaneda-Zuniga WR, Coleman CC, Herrera M, Amplatz K: Percutaneous technique in the management of urological complications. Radiology 148:407412, 1983. 47. Hart PL, Ingram DW, Peckman GB: Postnephrectomy arteriovenous fistula causing stroke and congestive heart failure. Can Med Assoc J 108:1400-1404, 1973. 48. Lacombe M: Arteriovenous fistulas of the renal pedicle following nephrectomy. Ann ChirThoracCardiovasc 12:91-97, 1973. 49. Goldstein AG, DeLaurentis DA, Schwartz A J : Postnephrectomy arteriovenous fistula. J Urol 98:44-47, 1974. 50. Castaneda-Zuniga WR, Tadavarthy SM, Murphy W, Beranek I, Amplatz K: Nonsurgical closure of large arteriovenous fistulas. JAMA 236:2649-2650, 1976. 51. Castaneda-Zuniga WR, Tadavarthy SM, Galliani C, Laerum F, Schwarten D, Amplatz K: Experimental venous occlusion with stainless steel spiders. Radiology 141:238241,1981.

Index


Index

Abdominal distension, 55 Abdominal radiography, 48, 53, 55-57 Abscess: diagnosis by ultrasonography, 252-53; intraabdominal, 55-56; pancreatic, 57-58; urologic, 1 29, 14245,204,244,249 Acquired immune deficiency syndrome, 40 Acute tubular necrosis: differentiation from rejection, 127, 201, 216, 227, 243; and graft failures, 234; and pulmonary edema, 36 — diagnosis: by angiography, 226-27; by radionuclide studies, 163-65; by ultrasonography, 243-44 Adhesions, 53 Aerobacter, 26 Alimentary tract complications, 49-56 Amphotericin B, 30 Amyloidosis, 12 Anastomosis: end-to-end, 208; end-toside, 208, 235, 266 Angiography: and arteriovenous fistulas, 266-67, 278-80, 292-94; in differentiation between rejection and acute tubular necrosis, 127; methodology, 202-3. See also Digital subtraction angiography ;Transluminalangioplasty — in diagnosis of: acute tubular necrosis, 226-27; gastrointestinal complications, 49, 51 -52; rejection, 1 27, 21624; renal papillary necrosis, 227; urologic complications, 151,1 54; vascular complications, 201, 204-15, 251,280-81,284 Antacids, 53, 145 Antilymphocyte globulin, 43 Antrectomy, 52 Appendicitis, 56 Arteriography, 202-3, 258, 260 Arteriosclerosis, 12 Arteritis, necrotizing, 217 Arthritis, 85,87,114-15,119, 121 Arthroplasty, 101 Ascites, 48 Aspergillus infections, 30-31, 39

Atelectasis, 33 Azathioprine, 25, 39-40, 43, 166

Balloon dilatation. See Gruntzig balloon dilatation Barium studies, 52, 57 Biliary tract disease, 57 Biopsy: in diagnosis of Aspergillus infections, 30; and graft rupture, 151, iliac crest bone, 67; needle, 22, 43, 154; open-lung, 22, 34, 43; percutaneous aspiration, 57-58, 234-35, 250-55, 265; ultrasonography and, 254 Bladder, 1 63, 1 65, 203, 236, 245, 24, 285 Bone resorption, 67-69 Bone scan, 114 Bronchoscopy, 22 Bursitis, olecranon, 119 Cadaver transplant: and acute tubular necrosis, 226, 243; differentiation of acute tubular necrosis and rejection in, 216; and gastrointestinal hemorrhage, 52; and graft rupture, 1 51; as risk factor for infection, 26; as risk factor for pulmonary edema, 36; survival rate of, 201, 234 Calcification, soft tissue, 8, 43, 57, 82, 119 Calculi, 129, 145,245,285 Caliectasis, 246 Candida infections, 31-32, 49, 52, 56, 150 Carcinoma, 39-40, 59, 1 51, 254 Cardiac abnormalities, 3-10 Cardiac complications, posttransplant, 11-17 Cardiomegaly, 4, 36 Cavitation, pulmonary, 26, 29-34 Chest X-ray, in diagnosis of: cardiac abnormalities, 3-10, 13; pulmonary complications, 22-44 Cholecystitis, 58 Cholelithiasis, 58 Cimetidine, 52 Coccidioides infections, 31-32 Colitis, 55 Colonoscopy, 52 Computed tomography, in diagnosis of: gastrointestinal complications, 49, 57; lymphomas, 254; pulmonary complications, 43; renal emphysema, 253; urologic complications, 128 Contrast medium: in angiography, 154, 203, 211, 227, 294; in digital sub-

302

Index

traction angiography, 257-60; in intravenous pyelography, 128-30,1 35; in nephrostograms and nephrostomy, 290-91; in transluminal angioplasty, 279-80 Contrast studies, 48 Corticosteroids. See Steroids Cryptococcus, 31-32 Cyclosporin A, 1 64, 1 66, 234 Cystography, 285 Cytomegalovirus infections: diagnosis of by radionuclide studies, 163,165; gastrointestinal, 48-49, 51-52, 57-58; incidence of reactivation of, 51; pulmonary, 23, 26, 32-36, 38; urinary tract, 150 Dehydration, 161 Diabetes mellitus: effects on the cardiovascular system, 12; and gastrointestinal complications, 53; and posttransplant mortality, 23; and pulmonary infections, 26; and renal papillary necrosis, 227; and skeletal complications, 82, 85, 100-101, 115, 121; and survival rates, 162-63; and urologic complications, 135, 150 Diabetic neuropathy, 101 Diarrhea, bloody, 52 Diethylenetriaminepentacetic acid (DTPA), 161,164-65 Digital subtraction angiography (DSA), 128,257-60 Diverticulitis,48,54 Diverticulosis, 52 Donors, 260 Dwarfism, 70,80 Dysphagia, 49 Echocardiography, 3-17 Electrocardiogram, 3-8 Embolization, 51, 265, 292-94 Emphysema, renal, 253 Empyema, pulmonary, 28-29, 44 Enemas, water-soluble contrast, 53, 55-

56 Enterocolitis, pseudomembranous, 56 Epiphyseal slippage, 70, 111-12 Escherichia coll, 26, 150 Esophageal varices, 49, 58 Esophagitis, 49 Esophagrams, 49

Ethanol abuse, 57 Extravasation, urinary, 127, 129-35, 285. See also Fistula Fibrosis, ureteropelvic, 129, 141, 24546,285 Fistula: bronchopleural, 43; pancreaticoduodenal, 58; renal arteriovenous, 130, 154,204,214,265-80,292-94; urinary, 129-35, 150. See also Extravasation Fistulogram, 267, 279-80 Fluid collections, perirenal: aspiration of, 254; differentiation from rejection, 216; types, 143; ultrasonography in diagnosis of, 236, 240, 244, 246-50, 254; and vascular obstruction, 204, 211, 280. See also Lymphocele Fractures: compression, 82; epiphyseal, 70, 111-12; osteochondral, 87; spontaneous, 85, 101-11,121 Furantoin, 43 Furosemide, 162, 165 Gallium scans, 145 Gangrene, 82, 115 Gastritis, erosive, 50, 52 Gastroduodenoscopy, 51 Gastroenteritis, 48 Gastrointestinal complications: of alimentary tract, 49-56; in children, 48; he.patobiliary,58; incidence of,47-48; malignancies, 59; mortality rate from, 47-48, 50, 52-54, 56; pancreatic, 56-58 Gastrointestinal hemorrhage, 47-48, 5052,163,166 Gastroscopy, 52 Glomerulonephritis, 12, 163, 165 Glucagon, 258 Growth retardation, 70, 85 Gruntzig balloon dilatation, 260, 27584,291 Hematemesis, 50 Hematoma, 142, 145, 161, 163, 165, 204,244,249 Hemodynamic studies, 8,1 3 Hemophilus influenza, 23 Hemorrhoids, 52 Heparin,279,283 Hepatic dysfunction, 26, 48-49, 58

Index Hepatitis, 47-48, 58 Hepatobiliary complications, 58 Hernias, 53 Herpes simplex virus, 40, 49,150 Hilar adenopathy, 34, 40 Histoplasma infections, 31-32 Hydronephrosis, 244-46 Hypercalcemia, 57, 82, 258 Hypercalciuria, 145 Hyperparathyroidism: in children, 70; and gastrointestinal complications, 48, 50, 57; posttransplant, 84; and skeletal complications, 65-67, 69, 70, 84, 100-101, 111, 113, 119; and urinary obstruction, 145 Hypertension: digital subtraction angiography in evaluation of, 258; effect of renal transplantation on, 12, 1 51 6; portal, 58; posttransplantation, 204, 280-81; and pulmonary edema, 36 Hypoalbuminemia, 51 Hypotension, 161, 249 Ileus, 53,55,56 Immunoblastomas. See Sarcomas Immunosuppression: and gastrointestinal complications, 48-49, 51, 53-54; and graft survival, 234; and malignancies, 151; and pulmonary complications, 21, 23-26, 29, 34, 38-39; and reactivation of cytomegalovirus infections, 51; and rejection, 21 8; and renal infection, 253; and skeletal complications, 85, 110-11, 114, 119; and urologic complications, 1 28-29, 1 35, 145,150-51,244 Infarction, 31, 56 Infections: bacterial, 23-30, 35, 54, 150; diagnosis by radionuclide studies, 163, 165-66; diagnosis by ultrasonography, 249, 252-53;fungal, 23-25, 29-33, 35, 39, 49, 52, 56, 150; gastrointestinal, 49; and graft failure, 234; due to perinephric fluid collections, 249, 250; protozoan, 23, 34-35; pulmonary, 20-36, 38-40, 44; and renal papillary necrosis, 227; skeletal, 114-15; urinary tract, 130, 150, 216, 244; viral, 23-25, 29, 3234,40,49,51-52,57-58, 150, 165 Infiltrates, pulmonary, 26-42 Intervention radiology, 265-94

303

Ischemia, renal cortical, 227, 240, 245 Ischemic bowel disease, 56 Joint aspiration, 114 Kaposi's sarcoma, 40, 52, 59 Kerley's lines, 36 Klebsiella infections, 21, 26 Laparotomy, 55 Leakage: lymphatic, 143, 248; urinary, 161, 165, 216, 248, 285; vascular, 1 65. See also Urinoma; Hematoma Legionella infections, 27 Lesions, atheromatous, 204 Leukemia, 31 Leukocytes, labeled, 165 Leukopenia, 26 "Looser's zones." See "Milkman's pseudofractures" Lymphocele: diagnosis by radionuclide studies, 161,163,1 65; diagnosis by ultrasound, 145, 244, 248; differentiation from rejection, 216; incidence and etiology, 143; and renal vein thrombosis, 154; treatment, 250; and vascular obstruction, 204, 285 Lymphomas, 39-40, 59, 151, 254 Magnetic resonance imaging (MRI), 244 Magnification radiography, 67 Malignancy: abdominal, 59; diagnosis by radionuclide studies, 163, 166; diagnosis by ultrasonography, 254; pulmonary, 31, 39-40; urologic, 1 30, 151,280,285 Measles, 33 Mediastinal lipomatosis, 20, 43 Melena, 50, 56 Microradiography, 67 "Milkman's pseudofractures," 70 Monilial infections. See Candida infections Mortality rates: from gastrointestinal complications, 47-48, 50, 52-54, 56; from pulmonary complications, 20-21, 34, 36, 38, 40; from urologic complications, 1 30, 135 Mycobacterium tuberculosis hominis, 26 Myocardial contractility, 7, 9-10 Necrosis: aseptic, 163,166; bowel, 53; cortical, 216;fibrinoid, 217;

304

Index

ischemic, 48; renal papillary, 1 30, 21 6, 227, 246; urcteral, 1 30, 1 35, 216, 285. See also Acute tubular necrosis Nephritis, intestinal, 12 Nephrograms, 202-3, 21 8-19, 227 Nephrostogram, 265, 285-91 Nephrostomy drainage, 265, 285-91 Nephrotoxicity, 163-64 Neuropathic joint disease, 85, 121 Nocardia, 23,29,44 Nuclear medicine, 3, 1 60-66, 234 Obstruction: diagnosis of, 237, 245-46, 251, 287; intestinal, 47-48, 53-54; outflow, 1 61 -65; due to perinephric fluid collections, 250; urologic, 127, 129, 135-48, 161-65,201, 203, 216, 227, 244-45, 258, 285-87; vascular, 201,204-14,217,244,251,279 Occlusion: arterial, 130,154, 164-65, 251; vascular, 216, 275 Orthoiodohippuric acid (OIH), 1 61, 1 64-65 Osteitis fibrosa, 65-67, 70, 83 Osteoarthritis, secondary, 87 Osteochondritis dissecans, 87 Osteodystrophy, renal, 64-121 Osteolysis, 69 Osteomalacia, 65-67, 70, 82-85 Osteomyelitis, 82,85, 114-15, 121 Osteonecrosis, 85, 87-101, 1 21 Osteopenia. See Osteoporosis Osteoporosis, 65, 67, 70, 80-85, 111, 163,166 Osteosclerosis, 65-70, 84 Ovarian cyst, 248 Oxalosis, 119 Pancreatic complications, 47-48, 56-58 Pancreatitis, 36, 47-48, 56-58 Parathyroid hormone, 66 Parathyroidectomy, 84 Parenchyma! complications, 216-24, 265 Peptic ulcer disease. See Ulceration, gastric Perforation: gastric, 50; intestinal,47-48,

53-56 Pericardia! constriction, 3, 8 Pericardia! effusion, 3, 6-10, 1 3 Pericarditis, acute, 3, 5, 7-8 Peritonitis, 54, 56

Phlebography, 211 Phycomycetes, 31, 39 Pittsburgh pneumonia agent, 27 Plasmocytoma,extramedullary intestinal,

59 Pleural effusion, 28, 34, 36, 44, 57 Pleuritis, 44 Pneumatosis cystoidis intestinalis, 56 Pneumococcus, 23, 26 Pneumocystis carinii infections, 23, 30,

32-36, 38 Pneumonia, 22-23, 28, 31, 35, 40, 42 Pneumoperitoneum, 55-56 Pneumothorax, 43 Polyarteritis nodosa, 217, 224 Polyps, 52 Prostatic hyperplasia, 148 Proteinuria, 211 Proteus, 150 Pseudocysts, 57-58 Pseudomonas infections, 26, 28 Pulmonary complications: diagnosis of, 22-23; incidence of, 20-21, 23-24; infectious, 20-35; mortality rate from, 20-21, 34, 36, 38, 40; noninfectious,

36-44 Pulmonary congestion, 3, 7, 9 Pulmonary edema, 23, 35-38, 44 Pulmonary embolism, 23, 30, 33, 38-39, 163,166 Pulmonary hemorrhage, 39,43 Pulmonary infections, 20-35 Pyelography, intravenous (IVP), 1 27-30, 134,141,235,246,249, 255, 285, 287 Pyelonephritis, 1 30, 148, 150,163,165, 227 Pyloroplasty,52 Radioisotope scanning, 43 Radionuclide scintigraphy, 135,1 61 -62, 165 Radionuclide studies: complications studied by, 1 63; in differentiation between rejection and acute tubular necrosis, 127, 164-65, 243; methodology, 160-62; ultrasonography and, 235,243-44,249 — in diagnosis of: abscesses, 253; gastrointestinal complications, 51-52,166; obstruction, 165; skeletal complications, 87-90, 166; urinomas, 249;

Index urologic complications, 135, 143, 145, 163-66, 285; vascular complications, 1 64-65 Reflux: esophageal, 49; vesicoureteral, 130,150,163 Rejection: acute, 21 6-1 8, 239-40, 243; angiography and, 224, 280; chronic, 216, 219, 224, 239, 243, 258; differentiation from acute tubular necrosis, 127, 201, 21 6, 227, 243; and gastrointestinal complications, 48, 52, 57; and graft failure, 234; and graft rupture, 151; hyperacute, 216, 239, 243; hypertension and, 204, 258, 280; and obstruction, 154, 211, 245, 280, 285-87; and osteonecrosis, 100; and perirenal fluid collections, 143, 247-48; and pulmonary complications, 23, 26, 30, 35-36, 38; radionuclide studies in diagnosis of, 16365; and renal papillary necrosis, 227; ultrasonography in diagnosis of, 23943,251 Renal rickets. See Osteomalacia Renograms, 161-62, 287 Roentgenography, 67, 70, 80-82, 87, 101,114,119 Rupture, allograft, 130, 151 Sarcomas, 59,151 Scintillation camera, 161 Scintillation probes, 161 Skeletal complications: posttransplant, 83-121; pretransplant, 64-82 Splenectomy,53, 162-63 Staphylococcus faecal is, 1 50 Staphylococcus infections, 23, 26, 28, 33,44,150 Stenosis: anastomotic, 204; aortal, 204; arterial, 154, 163-64, 201, 204, 20810, 258, 267-68; hypertension and, 280; secondary to rejection vasculitis, 205; treatment by transluminal angioplasty, 275, 279-84; vascular, 217; venous, 267 Steroids: and gastrointestinal complications, 48, 50-51, 54-58; and hepatobiliary complications, 58; and posttransplantation hypertension, 204, 258; and pulmonary complications, 25-26, 38, 43; and skeletal complications, 65, 85, 100-101, 166; in treat-

305

ment of rejection, 244; and urologic complications, 145, 166 Streptococcus infections, 23, 26 Strongyloides stercoralis, 35 Sulfonamides, 29,34 Survival rates, 162-63, 234 Tamponade, cardiac, 3, 8 Technetium sulfur colloid, 166 Tendon ruptures, 11 3 Thrombocytopenia, 39, 51 Thrombo-embolic disease, 20 Thrombophlebitis, 38 Thrombosis: arterial, 163-64, 201, 204, 214, 216; vascular, 216-25; venous, 130,154, 163-65,201,204,211 Transluminal angioplasty: of arteriovenous fistulas for chronic hemodialysis, 265-80; of transplanted renal arteries, 251,265,280-84 Transplantectomy, radical, 151 Tuberculosis, 26, 33,119 Ulceration: esophageal, 49; gastric, 4752; intestinal, 48, 50-52, 55 Ultrasonography: in differentiation between rejection and acute tubular necrosis, 127, 244; methodology, 234-37; therapeutic use, 254-55, 290 — in diagnosis of: abscesses, 252-53; acute tubular necrosis, 243, 244; gastrointestinal complications, 49, 57-58; malignancies, 254; rejection, 239-43; renal emphysema, 253; urologic complications, 134-35, 143, 151,244-51,287 Ureter: hypotonic, 163, 165; leakage of, 1 28, 216; necrosis of, 1 35, 21 6, 285; obstruction of, 1 35-41, 1 50, 165, 201,203,227,244-45, 258, 285 Urinary tract infections. See Infections Urinomas: incidence of, 142; and vascular obstruction, 204 — diagnosis: by intravenous pyelography, 285; by radionuclide studies, 1 61, 163, 165; by ultrasonography, 244, 248-49 Urography, excretory, 127, 1 34-35, 141,151,154,235,249 Urologic complications: causes of, 12829; diagnosis of, 127-29,134, 151,

306

Index

204, 244-51; extravasation, 1 30-35; and graft failure, 234; incidence of, 129, 244, 285; infection, 150; malignancies, 151; mortality rate from, 130, 1 35, obstruction, 1 35-4; reflux, 150; rupture, 151; types, 12930; vascular problems and, 154 Vagotomy, 52 Varicella infections, 33 Vasculitis, 51,205,224 Ventricular dilatation, 3, 5-7, 10,13 Ventricular hypertrophy, 3-4, 10,13 Vitamin 0,66,83-84,111 Voiding cysto-urethro-gram (VCUG), 128 Volvulus, 53

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