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THE YEAR IN RENAL MEDICINE VOLUME 1
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THE YEAR IN
RENAL MEDICINE VOLUME 1
EDITED BY
JEREMY LEVY Department of Renal Medicine, Hammersmith Hospital, London, UK
CLINICAL PUBLISHING OX F O R D
. . . ,
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Clinical Publishing an imprint of Atlas Medical Publishing Ltd Oxford Centre for Innovation Mill Street, Oxford OX2 0JX, UK Tel:
+44 1865 811116
Fax:
+44 1865 251550
Web: www.clinicalpublishing.co.uk Distributed by: Taylor & Francis Ltd 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487, USA E-mail:
[email protected] Taylor & Francis Ltd 23–25 Blades Court Deodar Road London SW15 2NU, UK E-mail:
[email protected] © Atlas Medical Publishing Ltd 2005 First published 2005 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, without the prior permission in writing of Clinical Publishing or Atlas Medical Publishing Ltd Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention A catalogue record for this book is available from the British Library ISBN 1 904392 39 3 ISSN 1742-3082 The publisher makes no representation, express or implied, that the dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publisher do not accept any liability for any errors in the text or for the misuse or misapplication of material in this work Project manager: Rosemary Osmond Typeset by Footnote Graphics Limited, Warminster, Wiltshire, UK Printed by T G Hostench SA, Barcelona, Spain
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Contents Contributors vii Foreword xi
Part I
Chronic renal failure 1.
Diabetic nephropathy 3 Merlin Thomas, Mark Cooper
2.
Peritoneal dialysis 23 Edwina Brown
3.
Anaemia in chronic renal failure 43 Iain Macdougall
4.
Cardiovascular disease 69 Robert Foley
Part II
Acute renal failure 5.
Prevention of acute radiocontrast nephropathy 91 Norbert Lameire
6.
Renal support in and treatment of acute renal failure 115 Frank Liu, Ravindra Mehta
7.
Glomerulonephritis 143 Gerald Appel, Alice Appel
8.
Vasculitis and lupus nephritis 165 David Jayne
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CONTENTS
Part III
End-stage renal disease 9.
Progression of chronic renal failure 193 Jonathan Fox, Bruce Mackinnon
10.
Haemodialysis 211 Ken Farrington
11.
Mineral metabolism and renal bone disease 233 Simon Steddon, Stanley Fan
12.
Transplantation 259 John Forman, Mohamed Sayegh
13.
Interstitial and tubular diseases 281 Jérome Rossert, Evelyne Fischer
Part IV
New developments 14.
Inherited renal disease 301 Marie Hogan, Vicente Torres
15.
Renal physiology: acid-base, potassium, calcium and blood pressure 327 Robert Unwin, Pedro Cutillas, Giovambattista Capasso
16.
Ethnicity and renal disease 343 Jeremy Levy
List of abbreviations 359 Index of papers reviewed 363 General index 377
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Editor and contributors Editor Jeremy Levy, MA, PhD, ILTM, FRCP Consultant Nephrologist, Department of Renal Medicine, Hammersmith Hospitals Trust, London, UK
Contributors Alice Sue Appel, PhD Research Associate, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, USA Gerald B Appel, MD Professor of Clinical Medicine, Columbia University College of Physicians and Surgeons, Columbia University Medical Center, New York, USA Edwina A Brown, DM, FRCP Professor of Renal Medicine and Consultant Nephrologist, Imperial College London, Charing Cross Hospital, Fulham Palace Road, London, UK Giovambattista Capasso, MD Professor of Nephrology, Chair of Nephrology, Second University of Naples, Italy Mark E Cooper, MB BS, PHD, FRACP Professor of Medicine and Director, Danielle Alberti Memorial Centre for Diabetes Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia Pedro Cutillas, PhD Research Associate, Proteomics Unit, Ludwig Institute for Cancer Research, University College London, UK Ken Farrington, MD, FRCP Consultant Nephrologist, Lister Hospital, Stevenage, Hertfordshire, UK Stanley L-S Fan, MRCP Consultant Nephrologist, Department of Renal Medicine and Transplantation, Bart’s and The London Hospital, London, UK
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CONTRIBUTORS
Evelyne Fischer, MD, PhD Research Associate, Unit of Gene Expression and Disease/CNRS URA 1644, Department of Developmental Biology, Pasteur Institute, Paris, France Robert N Foley, MB, MSC, FRCPC, FRCPI Director, Nephrology Analytical Services, Minneapolis Medical Research Foundation, Minneapolis, Minnesota; and Associate Professor, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA John P Forman, MD Instructor of Medicine, Harvard Medical School, Renal Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA Jonathan G Fox, BSc, MD, FRCP Consultant Nephrologist, Renal Unit, Glasgow Royal Infirmary, Glasgow, UK Marie Hogan, MB, BCH, MRCP Consultant, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, USA David Jayne, MD, FRCP Consultant in Nephrology and Vasculitis, Renal Unit, Addenbrooke’s Hospital, Cambridge, UK Norbert Lameire, MD, PhD Chief of the Renal Division, Department of Medicine, University Hospital, Ghent, Belgium Jeremy Levy, MA, PhD, ILTM, FRCP Consultant Nephrologist, Department of Renal Medicine, Hammersmith Hospitals Trust, London, UK Frank Liu, MD Fellow, Division of Nephrology, Department of Medicine, University of California at San Diego, California, USA Iain C Macdougall, BSc, MD, FRCP Consultant Nephrologist and Honorary Senior Lecturer, Department of Renal Medicine, King’s College Hospital, London, UK Bruce Mackinnon, BSc, MRCP(UK) Specialist Registrar in Nephrology, Renal Unit, Glasgow Royal Infirmary, Glasgow, UK Ravindra L Mehta, MD, FACP Professor of Clinical Medicine, Division of Nephrology, Department of Medicine, University of California at San Diego Medical Center, San Diego, California, USA
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CONTRIBUTORS
IX
Jérome Rossert, MD, PhD Professor of Nephrology and Consultant Nephrologist, Georges Pompidou European Hospital, INSERM U652, and Pierre and Marie Curie University, Paris, France Mohamed H Sayegh, MD, FAHA, FASN Professor of Medicine and Pediatrics, Transplantation Medicine Chair, Harvard Medical School; Director, Transplantation Research Center, Brigham and Women’s Hospital & Children’s Hospital Boston, Boston, Massachusetts, USA Simon Steddon, MRCP Specialist Registrar, Department of Renal Medicine and Transplantation, Bart’s and The London Hospital, London, UK Merlin C Thomas, MB CHB, PhD, FRACP Don Jacquot Research Fellow, Danielle Alberti Memorial Centre for Diabetes Complications, Baker Medical Research Institute, Melbourne, Victoria, Australia Vicente Torres, MD, PhD Professor of Medicine, Division Chair, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, USA Robert Unwin, BM, PhD, FRCP Professor of Nephrology and Physiology (St. Peter’s Chair of Nephrology), Centre for Nephrology, Royal Free and University College Medical School, University College, London, UK
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Foreword AJAY K SINGH MB MRCP(UK) Clinical Director, Renal Division, Brigham and Women’s Hospital Associate Professor of Medicine, Harvard Medical School, Boston, USA
This yearbook brings you the latest advances in kidney disease over the past year. The contributing authors utilize their extraordinary scientific knowledge to update us on progress in their respective fields, and in their efforts have covered all the main areas of nephrology. Two areas deserve particular mention. We are at the 50th anniversary of the first kidney transplant performed by a team led by Dr Joseph Murray at the Brigham and Women’s Hospital, for which he was awarded the Nobel Prize in Medicine. In 1954, Dr Murray could have hardly believed that his important accomplishments would herald the transplantation of virtually every organ, or that the discovery of more targeted drugs to suppress the immune system as it applies to transplantation would lead to more effective treatment of glomerulonephritis. Also, ninety years ago, Abel, Rowntree and Turner devised an apparatus for the dialysis of blood, and sixty years have elapsed since Willem Kolff, a young physician, built the first clinically usable dialyzer. Kolff’s machine, a huge rotating drum with a 40-metre cellulose acetate sausage skin membrane in a large liquid bath, was the precursor for modern dialysis. Chronic dialysis emerged in the 1970s and has since transformed itself into a big business with multiple chains that cross international borders to provide hundreds of thousands of people with kidney support treatment. Transplantation and dialysis represent important changes in nephrology, but one could scarcely discuss advances in nephrology without discussing advances in physiology, epidemiology, molecular nephrology, and glomerulonephritis. Dr Levy should be commended for recruiting a ‘who’s who’ of contributors to provide a timely update for practising nephrologists, researchers, trainees and students, and in particular to review their own field and comment on the most important papers over the last year.
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Part I Chronic renal failure
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1 Diabetic nephropathy MERLIN THOMAS, MARK COOPER
Introduction Diabetic nephropathy is one of the most important causes of both chronic kidney disease and end-stage renal failure (ESRF). In the USA and much of Europe, diabetes is the commonest cause of ESRF, and in many regions is increasing in incidence with the increasing prevalence of obesity and an ageing population of individuals from ethnic minorities with a strong predisposition to the development of diabetes. Over the last few years we have learned much about the natural history of diabetic nephropathy and the risks of progression from normal kidney structure and function to overt nephropathy and proteinuria, frequently leading to renal failure, and associated with hugely increased risks of cardiovascular morbidity and mortality. More recently, this has been associated with high-quality trial data on interventions that can reduce the risk of progression of diabetic kidney disease. There already exists a large literature on the benefits of using inhibitors of angiotensin-converting enzyme (ACE) in patients with type 1 diabetes to reduce the progression of renal impairment and reduce cardiovascular events. In addition, a number of trials have been reported using angiotensin receptor antagonists in patients with type 2 diabetes and microalbuminuria, and in those with overt nephropathy, demonstrating respectively significant reductions in progression to proteinuria and in worsening of renal function (using losartan, irbesartan and valsartan). These effects seemed to be independent of the lowering of blood pressure itself, since the use of other agents to achieve equivalent blood pressure control is not associated with similar risk reduction. To this end, these studies point towards the ultimate goal of being able to reduce significantly the rate of renal complications of diabetes. In this chapter we will look first at some recent work on the natural history of diabetic renal disease, then some experimental data on the possible mechanisms for renal damage in diabetes, and finally the benefits of various therapeutic interventions.
Natural history of diabetic nephropathy Diabetic nephropathy has generally been thought of in three phases: microalbuminuria (urinary albumin excretion 30–300 mg/day [20–200 µg/min]); macroalbuminuria or © Atlas Medical Publishing Ltd
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proteinuria (>300 mg/day [>200 µg/min]); and end-stage renal disease (ESRD). Microalbuminuria is the first clinical sign of diabetic damage to the kidney and is thought of as a harbinger of progressive kidney damage. Microalbuminuria also reflects a higher risk of cardiovascular disease and premature mortality. It is generally suggested that many (if not most) patients with microalbuminuria will progress to nephropathy, which will be followed by an inexorable decline in renal function. This may not be true.
✍
Regression of microalbuminuria in type 1 diabetes Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. N Engl J Med 2003; 348: 2285–93
B A C K G R O U N D . Perkins et al. reported, in a study based at the Joslin Clinic, Boston, the phenomenon of regression of microalbuminuria in type 1 diabetes. In 386 type 1 diabetic patients with persistent microalbuminuria followed over 6 years, the frequency of regression of microalbuminuria was examined. Regression was arbitrarily defined as a 50% reduction in urinary albumin excretion from one 2-year period to the next. I N T E R P R E T A T I O N . The researchers noted that regression of microalbuminuria occurred in over half of all patients, with a 6-year cumulative incidence of 58%. Only a minority of patients (19%) progressed to overt nephropathy (Table 1.1). Major factors linked to regression included a young age, a short duration of diabetes, good glycaemic control (glycated haemoglobin [HbA1c]
