OXFORD MEDICAL PUBLICATIONS Oxford Desk Reference Nephrology Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product informa- tion and clinical procedures with the most up-to-date pub- lished product information and data shee ts provided by the manufacturers and the most recent codes of conduct and safety regulation s. The authors and the publishers do not accept responsibility or legal liability for any e rrors in the text or for the misuse or misapplication of material in this work. 2 Except where otherwise stated, drug doses and recom- mendations are for the non-pregnant adult who is not breast-feeding. Oxford Desk Reference Nephrology Jonathan Barratt Senior Lecturer and Honorary Consultant Nephrologist, John Walls Renal Uni t, Leicester General Hospital, Leicester Kevin Harris Reader and Honorary Consultant Nephrologist, John Walls Renal Unit, Leicester General Hospital, Leicester and Peter Topham Reader and Honorary Consultant Nephrologist, John Walls Renal Unit, Leicester General Hospital, Leicester 1 1 Great Clarendon Street, Oxford OX2 6DP Oxford University Press is a department of the University of Oxford. It furthers the Univer sity \200\231s objective of excellence in research, scholarship, and education by publishin g worldwide in Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico Cit y Nairobi New Delhi Shanghai Taipei Toronto With of \201 ces in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan P oland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries Published in the United States by Oxford University Press Inc., New York Oxford University Press 2009 The moral rights of the author have been asserted Database right Oxford University Press (m aker) First published 2009 All rights reserved. No part of this publication may be reproduced, stored in a retrieval s ystem, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, or under terms agreed with t he appropriate reprographics rights organization. Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, a t the address above You must not circulate this book in any other binding or cover and you must impose this sam e condition on any acquirer British Library Cataloging in Publication Data Data available Library of Congress Cataloging in Publication Data Data available Typeset by Cepha Imaging Private Ltd., Bangalore, India Printed in CPI Antony Rowe, Chippen ham, Wiltshire ISBN 978 \200\2230 \200\22319 \200\223922956 \200\2237 10 9 8 7 6 5 4 3 2 1 v Preface In this era of evidence-based medicine, one of the biggest challenges confronting clinician s is keeping abreast with often rapidly changing recommendations that guide clinical practi ce. While it is clearly helpful to have research-based guidelines and protocols to draw upo n it is not always easy to access this information, particularly at the time when it is nee ded most, such as on a ward round or in a busy outpatient clinic. These evidence-based guid e- lines, produced by national organizations (The Renal Association, British Hypertension S ociety, National Institute for Health and Clinical Excellence) and international organiza- tions (International Society of Nephrology, National Kidney Federation \200\223 KDOQI) are often found in a variety of locations and published media and therefore timely access is n ot always possible. To overcome this problem we have aimed to produce a comprehensive textbook of nephrology wh ich focuses on aspects of renal disease that are important to the clinician. The book bring s together the key recommendations found in current evidence-based guidelines and presents them in a uniform and accessible format. It has been designed and written so that locating information is both quick and simple, and the layout of the chapters allows the reader to i dentify and assimilate information rapidly. The book is aimed at clinicians with a specialist interest in Nephrology (including con- su ltants and specialist trainees in Nephrology) but it should also prove to be a valuable res ource for any generalists who encounter a nephrological problem in their day-to-day practic e. We hope that this book will become an integral part of your working day. Dr Jonathan Barratt Dr Kevin Harris Dr Peter Topham vi Acknowledgements Many people are involved in the production of a book like this and it is impossible to reco gnize every contribution. We would, however, like to thank speci \201 cally the chapter au thors who without exception have produced work of the highest quality. In addition we thank Chris Reid, Helen Liepman, and Marionne Cronin from Oxford University Press who have been instrumental in driving the production of the book. Finally we owe particular thanks to our wives and children who have provided endless support, encouragement and patience during th e writing and editing process. vii Brief contents Detailed Contents ix Abbreviations xiii Contributors xvii 1 Assessment of renal disease 1 2 Fluid and electrolyte disorders 41 3 Glomerular disease 75 4 The kidney in systemic disease 143 5 Tubular disease 199 6 Chronic interstitial disease 225 7 Urinary tract infection 243 8 Renal stone disease 269 9 Hypertension 285 10 Acute kidney injury 317 11 Chronic kidney disease 389 12 Special problems in chronic kidney disease 461 13 Dialysis 479 14 Renal transplantation 543 15 Inherited renal disease 581 16 Structural and congenital abnormalities 645 BRIEF CONTENTS viii 17 Malignancy of the kidney and urinary tract 667 18 Pharmacology and drug use in kidney disease 689 Appendix 717 Index 737 ix Detailed contents 1 Assessment of renal disease 1 4.3 Plasma cell dyscrasias 158 4.4 Sarcoidosis 164 4.5 Systemic vasculitis 168 4.6 Mixed cr yoglobulinemia and hepatitis C infection 176 1.1 History and clinical examination of patients with renal disease 2 1.2 Urinalysis and microscopy 8 1.3 Clinical assessment of renal function 12 1.4 Renal func tion in the newborn infant 16 1.5 The aging kidney 18 1.6 1.7 Renal biopsy 32 1.8 4.7 Systemic lupus erythematosus 180 4.8 Scleroderma \200\223systemic sclerosis 186 4.9 Rhe umatoid arthritis, connective tissue Imaging in renal disease 20 diseases, and Sj gren \200\231s syndrome 188 4.10 Sickle cell neuropathy 192 4.11 Cancer and the kidney 196 Immunological investigation of renal disease 36 5 Tubular disease 199 2 Fluid and electrolyte 5.1 5.2 Fanconi syndrome 204 5.3 Renal tubular acidosis 208 5.4 Hypokalemic tubular disorde rs 214 5.5 Nephrogenic diabetes insipidus 220 Isolated defects of tubular function 200 disorders 41 2.1 Hypo-/hypernatremia: disorders of water balance 42 2.2 Hypo-/hyperkalemia 46 2.3 Hypo-/hypercalcemia 52 2.4 Hypo-/hyperpho sphatemia 56 2.5 Hypo-/hypermagnesemia 60 2.6 Clinical acid \200\223base disorders 64 6 Chronic interstitial disease 225 6.1 Analgesic nephropathy 226 6.2 Nonsteroidal anti-in \202 ammatory drugs and the kidney 228 3 Glomerular disease 75 6.3 Uric acid and the kidney 232 6.4 Nephrotoxic metals 236 6.5 Balkan nephropathy 238 6.6 Aristolochic acid nephropathy 3.1 Proteinuria and/or hematuria 76 3.2 Nephrotic syndrome 80 3.3 Minimal change disease 86 3.4 Focal segmental glomerulosclerosis 92 3.5 ( \200\230Chinese herb nephropathy \200\231) and other rare causes of chronic interstitial nephritis 240 Immunoglobulin A nephropathy and Henoch \200\223Sch nlein purpura 100 3.6 Membranous nephr opathy 106 3.7 Mesangiocapillary glomerulonephritis 112 3.8 Acute endocapillary 7 Urinary tract infection 243 7.1 Lower and upper urinary tract glomerulonephritis 116 infection in adults 244 3.9 Crescentic glomerulonephritis 120 3.10 Antiglomerular basement 7.2 Urinary tract infection in children 252 7.3 Renal tuberculosis or other mycobacterial i nfections 256 membrane (Goodpasture s) disease 124 3.11 Infection-related glomerulonephritis 128 3.12 Mal ignancy-associated glomerular 7.4 Schistosomiasis 260 7.5 Fungal infections and the kidney 264 disease 134 3.13 Glomerular disease in the tropics 138 8 Renal stone disease 269 8.1 Medical management of stone 4 The kidney in systemic disease 270 disease 143 4.1 Diabetes mellitus 144 4.2 Amyloid and immunotactoid 8.2 Surgical management of stone disease 274 8.3 Nephrocalcinosis 278 8.4 Renal stone disease in children 282 glomerulopathy 150 DETAILED CONTENTS x 9 Hypertension 285 13 Dialysis 479 9.1 Clinical approach to hypertension 286 9.2 Renovascular disease 292 9.3 Malignant hypert ension 300 9.4 Hypertensive children 304 9.5 Hypertensive disorders in pregnancy 310 13.1 Dialysis strategies 480 13.2 Vascular access 488 13.3 Hemodialysis, hemo \201 ltratio n and hemodia \201 ltration 494 13.4 Peritoneal dialysis 506 13.5 Adequacy of dialysis 518 13.6 Medical management of the d ialysis patient 528 13.7 Psychological aspects of 10 Acute kidney injury (AKI) 317 10.1 Clinical approach to AKI 318 10.2 Renal replacement therapies treatment for renal failure 538 in AKI 328 10.3 Dialysis and hemoperfusion 14 Renal transplantation 543 14.1 Selection and preparation of the recipient 544 treatment of acute poisoning 336 10.4 Glomerulonephritis, vasculitis, and nephrotic syndrome 340 10.5 Acute tubulointerstiti al nephritis 344 10.6 Hemolytic uremic syndrome 14.2 Assessment of live renal donors 548 14.3 Transplant surgery and surgical complications 552 and thrombotic thrombocytopenic purpura 348 14.4 Early management of transplant recipients 556 Immunosuppression for renal transplantation 560 10.7 Hepatorenal syndrome 352 10.8 Ischemic AKI 356 10.9 Pigment-induced AKI 362 10.10 AKI in tropical countries 366 10.11 AKI in infants and children 372 10.12 AKI in pregnancy 378 10.13 AKI in the elderly 384 14.5 14.6 Long-term medical complications of renal transplantation 566 14.7 Recurrent and de novo disease post renal transplantation 572 14.8 Outcome of renal transplantation 576 11 Chronic kidney disease (CKD) 389 11.1 Assessment of CKD 390 11.2 Endocrine disorders in CKD 398 11.3 Sexual disord ers in CKD 402 11.4 Hypertension in CKD 406 11.5 Cardiovascular risk factors in CKD 412 11. 6 Gastrointestinal disorders in CKD 418 11.7 Liver disorders in CKD 422 11.8 Hematological disorders in CKD 426 11.9 Skeletal disorders in CKD 432 11.10 B2-Microglobulin amyloidosis 15 Inherited renal disease 581 Investigation of inherited renal disease 582 15.2 Polycystic kidney disease 15.1 in children 586 15.3 Autosomal dominant polycystic kidney disease 590 15.4 Tuberous sclerosis 598 15.5 von Hippel \200\223Lindau disease 600 1 5.6 Nephronophthisis 602 15.7 Thin membrane nephropathy 606 15.8 Alport \200\231s syndrome 608 15.9 Nail \200\223patella syndrome 614 15.10 Congenital and infantile nephrotic syndrom e 616 in CKD 436 11.11 Immune function in CKD 440 11.12 Coagulation disorders in CKD 444 11.13 Dermatologic disorders in CKD 450 11.14 Neuropsychiatric disorders 15.11 Fabry disease 620 15.12 Other metabolic storage in CKD 454 disorders with renal involvement 624 12 Special problems in CKD 461 15.13 Cystinosis 628 15.14 Primary hyperoxalurias 632 15.15 Inherited disorders of purine 12.1 CKD in children 462 12.2 CKD in the elderly 468 12.3 CKD in diabetic patients 472 12.4 CKD in pregnancy 476 metabolism and transportation 636 15.16 Rare syndromes with renal involvement 640 DETAILED CONTENTS xi 16 Structural and congenital 18.3 Clinical use of diuretics 708 18.4 Systemic cancer therapies and abnormalities 645 16.1 Renal dysplasia 646 16.2 Vesicoureteric re \202 ux and re \202 ux the kidney 714 Appendix 717 nephropathy 648 Anatomy of the kidney and nephron 718 Calculations for acid \200\223base balance 16.3 Urinary tract obstruction 652 16.4 Congenital abnormalities of the and extracellular \202 uid volume 720 urinary tract 658 Calculations of the glomerular \201 ltration rate 722 16.5 Medullary sponge kidney 664 Relationship of glomerular \201 ltration 17 Malignancy of the kidney rate with age 723 and urinary tract 667 17.1 Tumors of the kidney 668 17.2 Wilms \200\231 tumor 672 17.3 Tumo rs of the renal pelvis Calculations of dialysis adequacy 724 Classi \201 cation of chronic kidney disease 726 Int ernet resources 727 Professional societies 728 Clinical practice guidelines and renal regis tries 729 and ureter 676 17.4 Tumors of the bladder 680 17.5 Tumors of the prostate 684 Information resources for professionals 730 Information resources for patients 18 Pharmacology and and carers 731 Patient counseling tools 732 Biochemistry conversion table 735 drug use in kidney disease 689 18.1 Handling of drugs in kidney disease 690 Index 737 18.2 Drug-induced nephropathies 698 This page intentionally left blank xiii Abbreviations ACEI ACR ADH ADMA ADPKD angiotensin-converting enzyme inhibitor albumin:creatinine ratio antidiuretic hormone asymm etric dimethyl arginine autosomal dominant polycystic kidney disease Acute Dialysis Quality Initiative anion gap advanced glycation end-products acquired immune de \201 ciency syndr ome acute interstitial nephritis acute kidney injury Acute Kidney Injury Network antinuclea r antibodies antineutrophil cytoplasmic antibodies automated peritoneal dialysis atheromato us renal artery stenosis angiotensin-receptor blocker autosomal recessive polycystic kidney disease atherosclerotic renovascular disease antistreptolysin O titre acute tubular necros is arteriovenous \201 stula abdominal X-ray twice daily bacillus Calmette \200\223Gu rin British National Formulary blood pressure congenital abnormalities of the kidneys and urin ary tract continuous ambulatory peritoneal dialysis continuous arteriovenous hemo \201 ltr ation continuous cycling peritoneal dialysis colony-forming units dose of complement requir ed to hemolyse 50% of erythrocytes chronic kidney disease cytomegalovirus calcineurin inhib itor central nervous system cyclo-oxygenase C-reactive protein continuous renal replacement therapy ciclosporin computed tomography central venous pressure CVVHF CVVHD CVVHDF continuous venovenous hemo \201 ltration continuous venovenous hemodialysis continuous ven ovenous hemodia \201 ltration chest X-ray diastolic blood pressure dual energy X-ray absor ptiometry diabetes insipidus disseminated intravascular coagulation diabetes mellitus dimer captosuccinic acid Dialysis Outcomes & Practice Patterns Study double-stranded DNA diethyle netriamine penta-acetic acid extracellular \202 uid electrocardiograph extended daily dia lysis ethylenediamine tetra-acetic acid epithelial sodium channel estimated glomerular \201 ltration rate equilibrated Kt/V enzyme-linked immunosorbent assay electon micrograph e xtractable nuclear antigen erythropoietin established renal failure erythropoiesis-stimulat ing agent erythrocyte sedimentation rate end-stage renal disease focal and segmental glomer ulosclerosis fractional excretion of sodium \201 bromuscular disease focal segmental glom erulosclerosis glomerular basement membrane glucose degradation products glomerular \201 ltration rate gastrointestinal hemotoxylin and eosin highly active antiretroviral therapy h omozygous sickle cell anemia hemodialysis hemodia \201 ltration Hemolytic anemia, Elevated Liver enzymes and Low Platelet count hemo \201 ltration heparin-induced thrombocytopenia human immunode \201 ciency virus CXR DBP DEXA DI DIC DM DMSA DOPPS ADQI AG AGE AIDS AIN AKI AKIN ANA ANCA APD ARAS ARB ARPKD dsDNA DTPA ECF ECG EDD EDTA ENaC eGFR eKt/V ELISA EM ENA EPO ERF ESA ESR ESRD FSGS FENa FMD FSGS GBM GDP GFR GI H&E HAART HbSS HD HDF HELLP ARVD ASOT ATN AVF AXR bd BCG BNF BP CAKUT CAPD CAVH CCPD cfu CH50 CKD CMV CNI CNS COX CRP CRRT CsA CT CVP HF HIT HIV ABBREVIATIONS xiv HMG CoA 3-hydroxy-3-methylglutaryl coenzyme A hemoperfusion high power \201 eld hepatorenal syndr ome hypertension hemolytic uremic syndrome immuno \202 uorescence intermittent hemodialysi s intermittent hemo \201 ltration interleukin intact parathyroid hormone International Soc iety of Peritoneal Dialysis intensive therapy unit intravenous intravenous urogram Kidney D isease Improving Global Outcomes Kidney Disease Outcomes Quality Iniative kidneys, ureters and bladder lactate dehydrogenase low density lipoprotein liver function tests low molecula r weight heparin left ventricle mercaptoacetylglycine molecular adsorbent recirculating sys tem micturating cystourethrogram Modi \201 cation of Diet in Renal Disease study mycopheno late mofetil magnetic resonance imaging molecular weight nocturnal intermittent peritoneal dialysis normalized protein catabolic rate National Health and Nutrition Examination Survey s National Institute for Health and Clinical Excellence (renamed in 2005) National Institut e of Diabetes and Digestive and Kidney Diseases National Kidney Foundation new-onset diabet es after transplantation nephronophthisis normalized protein equivalent of total nitrogen a ppearance nonsteroidal anti-in \202 ammatory drug nephrogenic systemic \201 brosis organ ic anion transporter-1 once daily OCPD PCR PD PE PET PeT pmp PNA optimized cycling peritoneal dialysis protein:creatinine ratio peritoneal dialysis plasma e xchange peritoneal equilibration test per-eclampsia per million population protein equivale nt of total nitrogen appearance per oral panel reactive antibodies pure red cell aplasia pr ostate-speci \201 c antigen polytetra \202 uoroethylene parathyroid hormone post-transpla nt lymphoproliferative disease pelviureteric junction four times daily renin \200\223angiot ensin \200\223aldosterone system renal blood \202 ow renal cell carcinoma radio contrast- induced nephropathy resistive index risk, injury, failure, loss, end-stage disease renal tu bular acidosis relative risk renal replacement therapy systolic blood pressure subcutaneous sclerosing encapsulating peritonitis subjective global assessment secondary hyperparathyro idism systemic in \202 ammatory response syndrome slow low-ef \201 ciency daily dialysis sympathetic nervous system standardized permeability analysis serum protein electrophoresis single-pool Kt/V standardized Kt/V systemic vascular resistance transitional cell carcinom a three times daily transjugular intrahepatic portosystemic shunt transmembrane pressure tu mor necrosis factor- tumor, node, metastases total parenteral nutrition transrectal ultra sound thrombotic thrombocytopenic purpura HP HPF HRS HTN HUS IF IHD IHF IL iPTH ISPD PO PRA PRCA PSA PTFE PTH PTLD ITU IV IVU K/DIGO PUJ qds RAS RBF RCC RCIN RI RIFLE K/DOQI KUB LDH LDL LFTs LMWH LV MAG3 MARS RTA RR RRT SBP SC SEP SGA SHPT SIRS MCUG MDRD MMF MRI MW NIPD SLEDD SNS SPA SPEP spKt/V stdKt/V SVR TCC tds TIPS nPCR NHANES NICE NIDDKD NKF NODAT NPHP nPNA TMP TNF- TNM TPN TRUS TTP NSAID NSF OAT-1 od xv ABBREVIATIONS TURBT transurethral resection of bladder tumor transurethral resection of prostate urea, creatini ne and electrolytes ultra \201 ltration unfractionated heparin urea kinetic modeling urine protein electrophoresis URR USRDS USS UTI VHL VUJ VUR urea reduction ratio US Renal Data System ultrasound scan urinary tract infection von Hippe l \200\223Lindau vesicoureteric junction vesicoureteric re \202 ux TURP U&Es UF UFH UKM UPEP This page intentionally left blank xvii Contributors Dr Samuel Ajayi Consultant Nephrologist Department of Medicine University of Abuja Teaching Hospital Abuja, FCT Nigeria Dr Anne Barton Reader and Honorary Consultant Rheumatologist ARC Epidemiology Unit Division of Epidemiology and Health Sciences Stopford Building Oxford Road Manchester Dr Reem Al Jayyousi Consultant Nephrologist and Honorary Senior Lecturer John Walls Renal U nit Leicester General Hospital Leicester Dr Linda M Barton Consultant Hematologist Department of Hematology Leicester Royal In \201 rmary Leicester Dr Karen Anderson Consultant Nephrologist The Richard Bright Renal Unit Southmead Hospital Bristol Dr Sunita Bavanandan Consultant Nephrologist Department of Nephrology Institute of Urology and Nephrology Hospital Kuala Lumpur Kuala Lumpur Malaysia Professor Mustafa Arici Professor of Medicine Hacettepe University Faculty of Medicine Depa rtment of Nephrology Ankara Turkey Professor Daniel Bichet Professor of Medicine and Physiology Renal Genetics Montreal Sacr -Coeur Hospital University of Montreal Quebec Canada Dr Richard Baines Clinical Lecturer in Nephrology John Walls Renal Unit Leicester General H ospital Leicester Dr Anne Blanchard Centers d \200\231Investigations Cliniques Hopital Europeen Georges Pompi dou Paris France Mr Ali Bakran Consultant Transplant & Vascular Surgeon Royal Liverpool University Hospital Liverpool Mr Adam Barlow Clinical Research Fellow Department of Transplant Surgery Leicester General Hospital Leicester Dr Detlef B ckenhauer Consultant Pediatric Nephrologist Department of Nephrology Great Orm ond Street Hospital for Children NHS Trust London Dr Jonathan Barratt Senior Lecturer and Honorary Consultant Nephrologist John Walls Renal U nit Leicester General Hospital Leicester Professor Nigel Brunskill Professor of Renal Medicine John Walls Renal Unit Leicester Gener al Hospital Leicester Professor Rashad Barsoum Professor of Medicine Kasr El-Aini Medical School Cairo University The Cairo Kidney Center Cairo Egypt Dr Katharine Buck Consultant Nephrologist Queen Margaret Hospital Dunfermline Mr Paul Butterworth Consultant Urological Surgeon Department of Urology Leicester General H ospital Leicester CONTRIBUTORS xviii Professor J Stewart Cameron Emeritus Professor of Renal Medicine Elm Bank Melmerby Penrith Cumbria Professor Chris Denton Professor of Experimental Rheumatology Department of Medicine Royal Free Campus University College London Professor Giovambattista Capasso Professor of Nephrology Department of Internal Medicine Se cond University of Naples Naples Italy Dr Stephen J Dickinson Specialist Registrar in Nephrology John Walls Renal Unit Leicester G eneral Hospital Leicester Dr Haresh Dodeja Consultant Nephrologist and Transplant Physician Wockhadt Hospitals Ltd Mu lund-Mumbai India Dr S J Carr Consultant Nephrologist and Honorary Senior Lecturer John Walls Renal Unit Leic ester General Hospital Leicester Dr Christopher Dudley Consultant Nephrologist The Richard Bright Renal Unit Southmead Hospi tal Bristol Dr Claire S Chapman Consultant Hematologist Department of Hematology Leicester Royal In \201 rmary Leicester Dr Tony Elliott Consultant Clinical Oncologist The Christie Hospital Withington Manchester Dr Chern Li Chow Specialist Registar in Nephrology Kidney Genetics Group Academic Nephrolog y Unit The Henry Wellcome Laboratories for Medical Research School of Medicine and Biomedic al Sciences University of Shef \201 eld Shef \201 eld Dr Hossam El Shazly Consultant Nephrologist Department of Renal Medicine Cairns Base Hospit al Cairns 4870 Australia Miss Alexandra J Colquhoun Specialist Registrar in Urology Department of Urology Leicester General Hospital Leicester Dr Sally Feather Consultant Pediatric Nephrologist Department of Pediatric Nephrology St Ja mes \200\231s University Hospital Leeds Professor Christian Combe Professor of Nephrology Center Hospitalier Universitaire de Borde aux Service de N phrologie Universit de Bordeaux, Unit INSERM U889 Bordeaux France Professor John Feehally Professor of Renal Medicine John Walls Renal Unit Leicester General Hospital Leicester Professor J rgen Floege Professor of Nephrology Division of Nephrology University Hospital Aachen Germany Dr Andrew Davenport Consultant Nephrologist and Honorary Senior Lecturer UCL Center for Nep hrology Royal Free & University College Medical School Hampstead Campus London Dr John Frew Registrar in Clinical Oncology Northern Center for Cancer Treatment Newcastle General Hospital Westgate Road Newcastle-upon-Tyne Dr Fr d ric Debelle Consultant Nephrologist Department of Nephrology H pital Erasme Univ ersit Libre de Bruxelles Brussels Belgium xix CONTRIBUTORS Dr Trevor Friedman Consultant Liaison Psychiatrist Brandon Unit Leicester General Hospital Leicester Dr Steve Harper Consultant Nephrologist The Richard Bright Renal Unit Southmead Hospital Br istol Dr Julian Gillmore Senior Lecturer and Honorary Consultant Nephrologist National Amyloidosi s Center Royal Free and University College Medical School Royal Free Hospital London Dr Kevin Harris Reader and Honorary Consultant Nephrologist John Walls Renal Unit Leicester General Hospital Leicester Professor Philip N Hawkins Professor of Medicine National Amyloidosis Center Department of Medicine Royal Free and University College Medical School Royal Free Hospital London Mr Leyshon Grif \201 ths Senior Lecturer and Honorary Consultant Urological Surgeon Urolog y Section Department of Cancer Studies & Molecular Medicine University of Leicester Clinica l Sciences Unit Leicester General Hospital Leicester Professor Friedhelm Hildebrandt Professor of Pediatrics and of Human Genetics Frederick G.L . Huetwell Professor for the Cure and Prevention of Birth Defects Doris Duke Distinguished Clinical Scientist University of Michigan Department of Pediatrics Ann Arbor Michigan USA Prof Krishan Lal Gupta Professor of Nephrology Postgraduate Institute of Medical Education and Research Chandigarh India Dr Pankaj Gupta Specialist Registrar in Chemical Pathology Leicester Royal In \201 rmary L eicester Dr Richard Holt Consultant Pediatric Nephrologist Royal Liverpool Children \200\231s Hospit al Alder Hey Liverpool Dr Shikha Gupta Specialist Registrar in Dermatology Leicester Royal In \201 rmary Leiceste r Prof Pascal Houillier Professor of Physiology Departement de Physiologie Hopital Europeen G eorges Pompidou Paris France Dr Jenny Hainsworth Clinical Psychologist Leicestershire Partnership NHS Trust and Leiceste r General Hospital Leicester Dr Andrew Hall Clinical Research Fellow Center for Nephrology Royal Free and University Col lege Medical School London Dr Peter Houtman Consultant Pediatrician Leicester Royal In \201 rmary Leicester Dr Alastair Hutchison Consultant Nephrologist Department of Renal Medicine Manchester Royal In \201 rmary Manchester Dr Matt Hall Specialist Registrar in Nephrology John Walls Renal Unit Leicester General Hos pital Leicester Dr David Jayne Consultant Nephrologist Renal Unit Addenbrookes Hospital Cambridge Dr Lorraine Harper Senior Lecturer and Honorary Consultant Nephrologist Division of Immunit y and Infection The Medical School University of Birmingham Edgbaston Birmingham Dr Graham Johnston Consultant Dermatologist Leicester Royal In \201 rmary Leicester CONTRIBUTORS xx Dr Caroline Jones Consultant Pediatric Nephrologist Royal Liverpool Children \200\231s Hosp ital Alder Hey Liverpool Dr Simon Maxwell Senior Lecturer in Clinical Pharmacology Queens Medical Research Institute Edinburgh Dr Catherine McBain Consultant Clinical Oncologist The Christie Hospital Withington Manches ter Dr Philip A Kalra Consultant Nephrologist and Honorary Senior Lecturer Dept of Renal Medici ne Hope Hospital Salford Professor John K Mellon Professor of Urology Urology Section Department of Cancer Studies & Molecular Medicine University of Leicester Clinical Sciences Unit Leicester General Hospit al Leicester Dr Jens Kannmacher Renal Fellow Division of Nephrology University Hospital Aachen Germany Professor Robert Kleta Professor of Nephrology Center for Nephrology Royal Free and Univers ity College Medical School London Dr Christopher Mitchell Consultant Pediatric Oncologist John Radcliffe Hospital Headington Oxford Mr Roger Kockelbergh Consultant Urological Surgeon Leicester General Hospital Leicester Dr Henry Morgan Consultant Pediatric Nephrologist Royal Liverpool Children \200\231s Hospit al Alder Hey Liverpool Dr George Kosmadakis Nephrologist and Clinical Research Fellow John Walls Renal Unit Leices ter General Hospital Leicester Dr Francis J Mussai Fellow in Pediatric Hematology and Oncology John Hopkins University Hos pital Baltimore Maryland USA Dr Andrew J P Lewington Consultant Nephrologist and Honorary Senior Lecturer Department of Renal Medicine St James \200\231s University Hospital Leeds Dr Chas Newstead Consultant Nephrologist Department of Renal Medicine St James \200\231s Un iversity Hospital Leeds Dr Robert Mactier Consultant Nephrologist Renal Unit Glasgow Royal In \201 rmary Glasgow Professor Michael Nicholson Professor of Transplant Surgery Department of Transplant Surger y Leicester General Hospital Leicester Dr Webster Madira Consultant Chemical Pathologist Leicester Royal In \201 rmary Leicester Dr Jo lle Nortier Head of the Department of Nephrology H pital Erasme Universit Libre d e Bruxelles Brussels Belgium Dr Stephen D Marks Consultant Pediatric Nephrologist Department of Nephrology Great Ormond Street Hospital for Children NHS Trust London Dr Albert CM Ong Reader and Honorary Consultant Nephrologist Kidney Genetics Group, Academi c Nephrology Unit The Henry Wellcome Laboratories for Medical Research School of Medicine a nd Biomedical Sciences University of Shef \201 eld Shef \201 eld Dr Nick Mayer Consultant Histopathologist Department of Pathology Leicester General Hospita l Leicester xxi CONTRIBUTORS Dr Rakesh S Patel Specialist Registrar in Nephrology and General Medicine John Walls Renal Unit Leicester General Hospital Leicester Dr John Schollum Consultant Nephrologist Department of Nephrology Dunedin Hospital Dunedin New Zealand Dr Sue Pavord Consultant Hematologist Leicester Royal In \201 rmary Leicester Dr John E Scoble Consultant Nephrologist New Guys House London Dr Henry Penn Clinical Research Fellow Center for Rheumatology Royal Free Hospital London Dr Adrian Stanley Consultant Physician and Clinical Pharmacologist Leicester Royal In \201 rmary Leicester Dr Liam Plant Consultant Nephrologist Department of Renal Medicine Cork University Hospital Cork Ireland Professor Vladisav Stefanovic Professor of Medicine Institute of Nephrology Faculty of Medi cine University of Nis Nis Serbia Dr Pradeep Rao Specialist Registrar in Psychiatry Brandon Unit Leicester General Hospital L eicester Dr Daniel Teta Consultant Nephrologist Privat-Docent & MER Service de N phrologie CHUV, 10 11 Lausanne Switzerland Dr Yvonne Rees Consultant Radiologist Department of Radiology Leicester General Hospital Le icester Mr James F Thorpe Clinical Research Fellow Department of Cancer Studies & Molecular Medicin e University of Leicester Professor Vincent Rigalleau Professor of Nutrition Center Hospitalier Universitaire de Bord eaux Service de Diab tologie Nutrition Universit de Bordeaux Bordeaux France Dr Charles Tomson Consultant Nephrologist The Richard Bright Renal Unit Southmead Hospital Bristol Dr Peter Topham Senior Lecturer and Honorary Consultant Nephrologist John Walls Renal Unit Leicester General Hospital Leicester Dr Alan D Salama Senior Lecturer and Honorary Consultant Nephrologist Renal Section Divisio n of Medicine Hammersmith Hospital London Dr Kjell Tullus Consultant Pediatric Nephrologist Department of Nephrology Great Ormond Str eet Hospital for Children NHS Trust London Dr Moin A Saleem Reader and Consultant Pediatric Nephrologist University of Bristol Childre n \200\231s Renal Unit Bristol Royal Hospital for Children Bristol Professor Robert Unwin St Peter \200\231s Professor of Nephrology Center for Nephrology Roy al Free and University College Medical School London Dr Andy Salmon Clinical Lecturer in Nephrology The Richard Bright Renal Unit Southmead Hosp ital Bristol Professor Jean-Louis Vanherweghem Emeritus Professor of Nephrology Department of Nephrology H pital Erasme Universit Libre de Bruxelles (ULB) Brussels Belgium Mr Richard FJ Stanford Clinical Research Fellow Department of Cancer Studies & Molecular Me dicine University of Leicester CONTRIBUTORS xxii Dr William Van \200\231t Hoff Consultant Pediatric Nephrologist Department of Nephrology Gr eat Ormond Street Hospital London Dr Christopher Winearls Consultant Nephrologist Oxford Radcliffe Hospitals Oxford Dr Matthias TF Wolf Senior Research Fellow Department of Pediatrics University of Michigan Ann Arbor Michigan USA Dr Stephen Walsh Clinical Research Fellow Center for Nephrology, Royal Free and University College Medical School, London Dr Graham Warwick Consultant Nephrologist John Walls Renal Unit Leicester General Hospital Leicester Dr Graham Woodrow Consultant Renal Physician Department of Renal Medicine St James \200\231 s University Hospital Leeds Professor Alan Watson Professor of Pediatric Nephrology Children \200\231s Renal and Urolog y Unit Nottingham University Hospitals Nottingham Dr Rosnawati Yahya Consultant Nephrologist Department of Nephrology Hospital Kuala Lumpur J alan Pahang Kuala Lumpur Malaysia Dr Rachel Westacott Specialist Registrar in Nephrology John Walls Renal Unit Leicester Gene ral Hospital Leicester Dr Janak R de Zoysa Consultant Nephrologist Department of Renal Medicine Auckland City Hosp ital Auckland New Zealand Dr Stanley White Senior Lecturer Institute of Membrane and Systems Biology University of Le eds Leeds 1 Chapter 1 Assessment of renal disease Chapter contents History and clinical examination of patients with renal disease 2 Urinalysis and microscopy 8 Clinical assessment of renal function 12 Renal function in the newborn infant 16 The agi ng kidney 18 Imaging in renal disease 20 Renal biopsy 32 Immunological investigation of ren al disease 36 J. FLOEGE AND J. KANNMACHER 2 History and clinical examination of patients with renal disease Dysuria Pain or discomfort during micturition is usually a result of bladder, prostatic or urethral in \202 ammation. Cystitis also causes frequency and urgency of micturition. Peri neal or rectal pain in men indicates prostatitis. A patient with renal disease can present in different ways: \200 The patient complains of a symptom or shows physical signs typically associated with renal disease. The patient is asymptomatic and comes to attention through pathological results of clinical or laboratory examination. Disorders of urine volume Polyuria Urine output of >3 L per day is de \201 ned as polyuria . It is often dif \201 cult for patients to differentiate between polyuria and frequency. Thus the measurement of daily urine excre- tion is necessary to elucidate the symptom. In m any cases patients complain of thirst instead of increased urine volume. The possible cause s for polyuria are listed in Table 1.1.2. A systemic disease is diagnosed that can lead to renal involvement. The patient is examined because he has been exposed to nephrotoxic agents. The family history of the patient reveals inherited renal disorders. Investigation methods which often lead to the detection of asymptomatic renal patients are biochemical analysis, urine analysis and blood pressure measurement. Cardinal symptoms sugg esting underlying renal disease are disorders of micturition, disorders of urine volume, al tera- tion in urinary composition, edema, loin pain and hyper- tension. Furthermore there i s a large variety of symptoms or medical problems associated with advanced renal failure an d uremia respectively (Table 1.1.1). Oliguria A reduction in urine volume to <500 mL per day indicates AKI leading to a situatio n in which homeostasis cannot be maintained. Anuria The sudden development of urine output of <100 mL per day is most commonly due to ob struction of the urinary tract. Other possible causes are renal infarction or cortical necr osis. Disorders of micturition Frequency Frequent emptying of the bladder can be associated with normal or increased urine volume (polyuria). The former may be due to in \202 ammation, st one or tumor of the bladder or a reduced bladder capacity. Frequency is often accom- panied with nocturia. Table 1.1.2 Conditions which may cause polyuria Increased renal water loss Endocrinologic disorders Central (cranial) diabetes insipidus Poor urinary stream The most common cause is prostatic enlargement in men past middle age. Urethral obstruction leads to retention and back pressure. Addison \200\231s disease Hyporeninemic hypoaldosteronism Renal tubular disorders Nephrogenic diabetes insipidus Acquired tubular defects, e.g. salt-losing nephropathy Table 1.1.1 Typical symptoms and complications in patients with advanced renal failure Pyelonephritis - Analgesic nephropathy - Multiple myeloma - Obstructive uropathy - Sarcoido sis - Hypercalcaemia, chronic potassium Malaise, weakness, diminished appetite, sleep disorders, headache General nonspeci \201 c symptoms Water overload, dehydration, hyperkalemia, metabolic acidosis Water \200\223electrolyte, acid \200\223base imbalance depletion Anorexia, nausea and regurgitation, peptic ulcer, gastrointestinal bleeding, diverticulosis Gastroenterological problems Toxic agents (e.g. aminoglycosides, lithium, cisplatinum) Diuretic therapy Bartter \200\231 s syndrome Polyuric phase of acute or acute-on- chronic renal failure Hypertension, pulmonary edema, pleurisy, pericarditis, cardiomyopathy, cardiac arrhythmia Cardiovascular and pulmonary problems Secondary hyperparathyroidism, osteomalacia, infertility, disturbance of growth in children Endocrinological and metabolic problems Osmotic diuresis Glycosuria in diabetes mellitus Administration of mannitol Peripheral polyneuropathy, restless legs syndrome, cramps, seizures, tremor, coma Neuromuscular problems Administration of large volume of contrast agents Increased water intake Many different skin alterations, such as palor, hyperpigmentation, pruritus, scratch marks Dermatological disorders Psychogenic Medication Drugs causing xerostomia or thirst (e.g. anticholinergics or clonidine) Renal anemia, bleeding tendency, immunode \201 ciency Hematological and immunological disorders CHAPTER 1.1 History and clinical examination of patients with renal disease 3 Alteration in urinary composition Hematuria Hematuria may originate from any part of the re nal tract and there are many possible underlying conditions, such as glomerulonephritis, in fection, calculi, tumors, thrombocy- topenia or disordered coagulation. \200 The most com mon cause is urinary tract infection. \200 Recurrent macroscopic hematuria is often seen in IgA nephropathy, but may also be due to intermittent bleed- ing from a structural lesion . hepatic disease, or increased capillary permeability due to allergy, in \202 ammation or i schemia. As a consequence of long-term renal failure or nephrotic syndrome, up to 20 additi onal liters of \202 uid can accumulate in the body, leading to generalized swelling calle d anasarca. In advanced \202 uid overload, interstitial pulmonary edema is common. Admini stration of drugs such as calcium-channel antagonists and steroids or diuretic abuse may al so lead to edema. Pain If pain occurs as a symptom of renal disease, it mostly indi- cates inflammation or ob struction. Pain arising from pyelonephritis usually develops gradually and has a con- stant intensity, whereas an acute obstruction typically causes a sudden severe and colicky pain radiating to the scrotum or groin. Blood from the urethra only appears in the initial urinary stream.