Chronic kidney disease, dialysis, and transplantation : a companion to Brenner and Rector's the kidney

897 Pages·2005·19.012 MB·English

by  Brian J G Pereira, Mohamed H Sayegh, Peter Gerard Blake

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Chronic Kidney Disease,Dialysis,and Transplantation ISBN:1-4160-0158-1
A Companion to Brenner and Rector’s The Kidney
Second Edition
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Nephrology is an ever-changing field.Standard safety precautions must be followed,but as new research and
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Library ofCongress Cataloging-in-Publication Data
Chronic kidney disease,dialysis,and transplantation :a companion to Brenner and
Rector’s the kidney / [edited by Brian J.G.Pereira,Mohamed Sayegh,Peter Blake.–2nd ed.
p.;cm.
Rev.ed.of:Dialysis and transplantation / [edited by] William F.Owen Jr.,Brian J.G.
Pereira,Mohamed H.Sayegh.1st ed.c2000.
Includes bibliographical references and index.
ISBN 1-4160-0158-1
1.Hemodialysis.2.Kidneys–Transplantation.I.Pereira,Brian J.G.II.Sayegh,
Mohamed H.III.Blake,Peter Gerard,1956- IV.Dialysis and transplantation.V.Brenner
& Rector’s the kidney.
[DNLM:1.Renal Dialysis.2.Kidney Failure,Chronic–therapy.3.Kidney
Transplantation.WJ 378 C55675 2005]
RC901.7.H45D5226 2005
616.6′1–dc22
2004051160
Acquisitions Editor:Susan Pioli
Developmental Editor:Alison Nastasi
Publishing Services Manager:Joan Sinclair
Project Manager:Cecelia Bayruns
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
To my wife,Sunita,
and children,Natasha and Nikhil,
for their constant support and understanding
To my mentors,
Drs.Kirpal Chugh,Nicolaos Madias,
and Andrew Levey
Brian J.G.Pereira
To my two brothers,
Dr.Sard H.Sayegh and Abdul Hafiz H.Sayegh,
for their continuous support ofmy career
through the years
Mohamed H.Sayegh
Thank you to Rose
for all her love and support
and to Matthew and Andrew
for keeping me grounded
Peter G.Blake
ix
Contributors
Stuart Abramson,M.D.,M.P.H. Glenn M.Chertow,M.D.,M.P.H.
Maine Nephrology Associates,Portland,Maine Associate Professor,Division ofNephrology,Department of
Medicine,University ofCalifornia,San Francisco,School of
Miriam J.Alter,Ph.D. Medicine,San Francisco,California
Associate Director for Epidemiologic Science,Division of
Viral Hepatitis,Centers for Disease Control and Prevention, William R.Clark,M.D.
Atlanta,Georgia Clinical Assistant Professor ofMedicine,Indiana University
School ofMedicine;Baxter Healthcare,Indianapolis,Indiana
Matthew J.Arduino,M.S.,Dr.P.H.
Supervisory Research Microbiologist,Division ofHealthcare Allan J.Collins,M.D.,F.A.C.P.
Quality Promotion,Centers for Disease Control and Professor ofMedicine,University ofMinnesota,
Prevention,Atlanta,Georgia Minneapolis,Minnesota
George R.Aronoff,M.D.,F.A.C.P. JosefCoresh,M.D.,Ph.D.,M.H.S.
Professor ofMedicine and Pharmacology;Chief,Division of Professor,Departments ofEpidemiology and Biostatistics,
Nephrology,Department ofMedicine,University of Johns Hopkins University School ofHygiene and Public
Louisville School ofMedicine,Louisville,Kentucky Health;Professor,Department ofMedicine,Johns Hopkins
University School ofMedicine,Baltimore,Maryland
Vaidyanathapuram S.Balakrishnan,M.D.,M.R.C.P.
Assistant Professor,Tufts University School ofMedicine,
Bryan M.Curtis,M.D.,F.R.C.P.C.
Division ofNephrology,DepartmentofMedicine,Tufts-New
Kidney Foundation ofCanada Research Fellow,Division of
England Medical Center,Boston,Massachusetts
Nephrology and Clinical Epidemiology Unit,Patient
Research Centre,Health Sciences Centre,Memorial
Joanne M.Bargman,M.D.,F.R.C.P.C.
University ofNewfoundland Faculty ofMedicine,St.John’s,
Professor ofMedicine,University ofToronto;StaffNephro-
Newfoundland,Canada
logist,University Health Network,Toronto,Ontario,Canada
Gabriel M.Danovitch,M.D.
Peter G.Blake,M.B.,F.R.C.P.C.,F.R.C.P.I
Professor ofMedicine and Medical Director,Kidney
Professor ofMedicine,University ofWestern Ontario,Chair
Transplant Program,University ofCalifornia,Los Angeles,
ofNephrology,London Health Sciences Center,London,
David Geffen School ofMedicine,Los Angeles,California
Ontario,Canada
Simon J.Davies,M.D.,F.R.C.P.
Joseph V.Bonventre,M.D.,Ph.D.
Professor,Institute ofScience and Technology in Medicine,
Professor ofMedicine,Harvard Medical School;Division
Keele University,Keele,England;Clinical Director,
Chief,Renal Section,Brigham and Women’s Hospital,
Department ofNephrology,University Hospital ofNorth
Boston,Massachusetts
Staffordshire,Stoke-on-Trent,England
Marilia Cascalho,M.D.,Ph.D.
Francis L.Delmonico,M.D.
Director,Transplantation Biology,Departments ofSurgery,
Professor ofSurgery,Harvard Medical School;Director of
Immunology and Pediatrics,Mayo Clinic,Rochester,
Renal Transplantation,Massachusetts General Hospital,
Minnesota
Boston,Massachusetts
Vimal Chadha,M.D.
Assistant Professor ofPediatrics,Virginia Commonwealth Laura M.Dember,M.D.
University Medical Center,Chair,Section ofPediatric Associate Professor ofMedicine,Boston University School of
Nephrology,Richmond,Virginia Medicine;Director ofDialysis,Boston University Medical
Center,Boston,Massachusetts
Christopher T.Chan,M.D.,F.R.C.P.C.
Medical Director-Home Hemodialysis,Division of Thomas A.Depner,M.D.
Nephrology,Toronto General Hospital,University Health Professor,Department ofInternal Medicine,University of
Network;Assistant Professor–Faculty ofMedicine,University California,Davis,School ofMedicine;Medical Director,
ofToronto,Toronto,Ontario,Canada University Dialysis Clinic,Sacramento,California
Anil Chandraker,M.D.,C.H.B.,M.R.C.P. Rita De Smet,M.Sc.,Ing.
Transplant Research Center,Brigham and Women’s Hospital, Renal Division,Department ofInternal Medicine,University
Boston,Massachusetts Hospital Ghent,Ghent,Belgium
x Contributors
Bradley S.Dixon,M.D. OlofHeimbürger,M.D.,Ph.D.
Associate Professor,Department ofInternal Medicine, Division ofRenal Medicine,Department ofClinical Science,
University ofIowa,Iowa City,Iowa Karolinska Instituet,and Senior Physician,Department of
Renal Medicine,Karolinska University Hospital at Huddinge,
Jeremy S.Duffield,M.R.C.P.,Ph.D. Stockholm,Sweden
Renal Fellow/NKRF Senior Fellow,Harvard Institutes of
Medicine (BWH),Boston,Massachusetts J.Harold Helderman,M.D.
Professor ofMedicine,Microbiology,and Immunology;
Nahel Elias,M.D. Chief,Renal Transplant Program;Medical Director,
Department ofSurgery,Harvard Medical School; Vanderbilt Transplant Center,Vanderbilt University Medical
Massachusetts General Hospital,Boston,Massachusetts Center,Nashville,Tennessee
Joseph A.Eustace,M.B.,M.H.S.,M.R.C.P.I. Lee W.Henderson,M.D., F.A.C.P.
Assistant Professor,Departments ofMedicine and Renal Division,Baxter Healthcare Corporation,McGaw
Epidemiology,Johns Hopkins University School ofMedicine; Park,Illinois
Medical Director,Bond Street Dialysis Unit,Johns Hopkins
University Hospital,Baltimore,Maryland Jonathan Himmelfarb,M.D.
Clinical Professor ofMedicine,University ofVermont College
Martin S.Favero,Ph.D. ofMedicine,Burlington,Vermont;Director ofNephrology
Director,Scientific and Clinical Affairs,Advanced and Transplantation,Maine Medical Center,Portland,Maine
Sterilization Products,Johnson & Johnson,Irvine,California
Michelle Hladunewich,M.D.
Steven Fishbane,M.D. Assistant Professor ofMedicine,University ofToronto
Associate Professor ofMedicine,State University ofNew Hospitals,Toronto,Ontario,Canada
York (SUNY) at Stony Brook School ofMedicine,Stony
Brook,New York;Director ofthe Dialysis Network,Associate Zhongping Huang,M.D.
Chairman ofMedicine,and Associate Director of Department ofMechanical Engineering,University of
Nephrology,Winthrop-University Hospital,Mineola, Kentucky,Lexington,Kentucky
NewYork
Bertrand L.Jaber,M.D.
Jay A.Fishman,M.D. Assistant Professor,Tufts University School ofMedicine;
Director,Transplant Infectious Disease & Compromised Vice-Chairman,Department ofMedicine Caritas-
Host Program,Massachusetts General Hospital;Associate St.Elizabeth’s Medical Center,Boston,Massachusetts
Professor ofMedicine,Harvard Medical School,Boston,
Massachusetts Dicken S.C.Ko,M.D.,F.R.C.S.(C.),F.A.C.S.
Assistant Professor ofSurgery,Departments ofSurgery and
Dayong Gao,Professor Urology,Harvard Medical School;Massachusetts General
UK Alumni Professor ofMechanical Engineering, Hospital,Boston,Massachusetts
University ofKentucky,College ofEngineering,
Department ofMechanical Engineering,Lexington, Holly Kramer,M.D.,M.P.H.
Kentucky Department ofPreventive Medicine and Epidemiology,
Loyola University Medical Center,Maywood,Illinois
John S.Gill,M.D.,M.S.
Assistant Professor ofMedicine,University OfBritish Alan M.Krensky,M.D.
Columbia,St.Paul’s Hospital,Vancouver,B.C.,Canada; Stanford University,Stanford,California
Adjunct Assistant Professor,Division ofNephrology,
Department ofMedicine,Tufts-New England Medical Richard Lafayette,M.D.
Center,Boston,Massachusetts Associate Professor ofMedicine;Associate Chairman,
Clinical Affairs,Department ofMedicine,Stanford University
Griet Glorieux,M.Sc.,Ph.D. School ofMedicine;Clinical Chief,Division ofNephrology,
Renal Division,Department ofInternal Medicine,University Stanford University Medical Center,Stanford,California
Hospital Ghent,Ghent,Belgium
Norbert Hendrik Lameire,M.D.,Ph.D.
Simin Goral,M.D. Professor ofMedicine,Renal Division,Department ofInternal
Associate Professor ofMedicine,Division ofNephrology, Medicine,University Hospital Ghent,Ghent,Belgium
University ofPennsylvania Medical Center,Philadelphia,
Pennsylvania James P.Lash,M.D.
Associate Professor ofClinical Medicine;Program Director,
William E.Harmon,M.D. Nephrology Fellowship,Section ofNephrology,Department
Division ofNephrology,Department ofMedicine,Harvard ofMedicine,University ofIllinois at Chicago College of
Medical School;Department ofNephrology,Children’s Medicine;University ofIllinois at Chicago Medical Center,
Hospital,Boston,Massachusetts Chicago,Illinois
Contributors xi
Adeera Levin,M.D.,F.R.C.P.C. Anupama Mohanram,M.D.
Professor ofMedicine,Division ofNephrology,University of Renal Fellow,UT Southwestern Medical Center,Dallas,Texas
British Columbia Faculty ofMedicine;St.Paul’s Hospital,
Vancouver,British Columbia,Canada Donald A.Molony,M.D.
Professor ofMedicine,Department ofInternal Medicine,
John K.Leypoldt,Ph.D. Division ofRenal Diseases and Hypertension,University of
Research Professor ofMedicine and Adjunct Professor of Texas Houston Medical School,Houston,Texas
Bioengineering,Dialysis Program,University ofUtah;
Veterans Affairs Salt Lake City Health Care System,Salt Lake Bhamidipati V.R.Murthy,M.D.,D.M.
City,Utah Assistant Professor,Department ofInternal Medicine,
Division ofRenal Diseases and Hypertension,University of
Philip Kam-Tao Li,M.D.,F.R.C.P.,F.A.C.P. Texas Houston Medical School,Houston,Texas
ChiefofNephrology and Consultant Physician,Department
ofMedicine & Therapeutics,Prince ofWales Hospital; Nader Najafian,M.D.
Chinese University ofHong Kong,Hong Kong Instructor ofMedicine,Harvard Medical School;Renal
Division,Brigham and Women’s Hospital;Transplantation
Orfeas Liangos,M.D. Research Center,Brigham and Women’s Hospital and
Clinical Research Fellow,Division ofNephrology,Tufts-New Children’s Hospital,Boston,Massachusetts
England Medical Center,Boston,Massachusetts
Cynthia Nast,M.D.
Colm C.Magee,M.D.,M.P.H. Professor ofPathology,Department ofPathology,
Instructor in Medicine,Harvard Medical School,Staff David Geffen School ofMedicine at UCLA and Cedars Sinai
Physiscian Renal Division,Brigham and Women’s Hospital, Medical Center,Los Angeles,California
Boston,Massachusetts
Gihad E.Nesrallah,M.D.,F.R.C.P.C.,F.A.C.P.
Naveed Masani,M.D. StaffNephrologist,Division ofNephrology,Department of
Attending Nephrologist,Winthrop-University Hospital, Internal Medicine,Humber River Regional Hospital,
Mineola,New York Toronto,Ontario,Canada
Tahsin Masud,M.D. Daniel Norman,M.D.
Assistant Professor ofMedicine,Department ofMedicine, Division ofPulmonary,Critical Care and Sleep Medicine,
Renal Division,Emory University School ofMedicine, Beth Israel Deaconess Medical Center,Harvard Medical
Atlanta,Georgia School,Boston,Massachusetts
Philip McFarlane,M.D.,F.R.C.P.C. Brenda M.Ogle,Ph.D.
Associate Professor ofMedicine,University ofToronto Director,Transplantation Biology,Departments ofSurgery,
Faculty ofMedicine;Medical Director,Home Dialysis, Immunology and Pediatrics,Mayo Clinic,Rochester,
Division ofNephrology,St.Michael’s Hospital,Toronto, Minnesota
Ontario,Canada
Yvonne M.O’Meara,M.D.
Ravindra L.Mehta,M.B.B.S.,M.D.,F.A.C.P. Department ofNephrology,Mater Hospital,Dublin,Ireland
Professor ofClinical Medicine,Associate Chair for Clinical
Affairs,Department ofMedicine,Division ofNephrology, Dimitrios G.Oreopoulos,M.D.,Ph.D.,F.R.C.P.C.,F.A.C.P.
University ofCalifornia,School ofMedicine,San Diego, Professor ofMedicine,Toronto Western Hospital,Toronto,
California Ontario,Canada
David C.Mendelssohn,M.D.,F.R.C.P.C. Brian J.G.Pereira,M.D.,M.B.A.
Associate Professor ofMedicine,University ofToronto Professor ofMedicine,Tufts University School ofMedicine,
Faculty ofMedicine,Toronto,Ontario,Canada;Head, President and ChiefExecutive Officer,NEHCF,Tufts-New
Division ofNephrology,Medical Director ofDialysis, England Medical Center,Boston,Massachusetts
Humber River Regional Hospital,Weston,Ontario,Canada
Phuong-Chi T.Pham,M.D.
William E.Mitch,M.D. Associate Professor ofMedicine,Division ofNephrology,
Edward Randall Distinguished Professor ofMedicine; Department ofMedicine,David Geffen School ofMedicine
Department ofMedicine,University ofTexas Medical atUCLA and Olive View–UCLA Medical Center,Sylmar,
Branch at Galveston,Galveston,Texas California
Sharon M.Moe,M.D. Phuong-Thu T.Pham,M.D.
Associate Professor ofMedicine,Associate Dean for Research Assistant Professor ofMedicine,Nephrology Division,
Support,Indiana University School ofMedicine;Director of Kidney and Pancreas Transplantation,Department of
Nephrology,Wishard Memorial Hospital,Indianapolis, Medicine,University ofCalifornia,Los Angeles,David
Indiana Geffen School ofMedicine,Los Angeles,California
xii Contributors
Andreas Pierratos,M.D.,F.R.C.P.C. Robert Thomas,MD
Associate Professor ofMedicine,University ofToronto Division ofPulmonary,Critical Care and Sleep Medicine,
Faculty ofMedicine,Toronto,Ontario,Canada;Humber Beth Israel Deaconess Medical Center,Harvard Medical
River Regional Hospital,Weston,Ontario,Canada School,Boston,Massachusetts
Jeffrey L.Platt,M.D. Jerome Tokars,M.D.,M.P.H.
Director,Transplantation Biology,Departments ofSurgery, Medical Epidemiologist,Division ofHealthcare Quality
Immunology and Pediatrics,Mayo Clinic,Rochester,Minnesota Promotion,Centers for Disease Control and Prevention,
Atlanta,Georgia
Sarah Prichard,M.D.,F.R.C.P.C.
Professor ofMedicine,Division ofNephrology,Department Robert D.Toto,M.D.
ofMedicine,McGill University Faculty ofMedicine, Professor ofMedicine;Director,Patient-Oriented Research
Montreal,Quebec,Canada in Nephrology,University ofTexas Southwestern Medical
Center,Dallas,Texas
Emilio Ramos,M.D.
University ofMaryland School ofMedicine,Division of Kathryn Tuohy,M.D.
Nephrology,Baltimore,Maryland Division ofGeneral Internal Medicine,Brown Medical
School;Rhode Island Hospital,Providence,Rhode Island
Madhumathi Rao,M.D.,F.R.C.P.(U.K.)
Instructor ofMedicine,Division ofNephrology,Department Raymond Camille Vanholder,M.D.,Ph.D.
ofMedicine,Turfts University School ofMedicine;Tufts- Professor ofMedicine,Renal Division,Department of
New England Medical Center,Boston,Massachusetts Internal Medicine,University Hospital Ghent,Ghent,
Belgium
Denise Sadlier,M.B.,M.R.C.P.I.
Department ofMedicine and Therapeutics,Mater Vassilis Vargemezis,M.D.
Misericordiae University Hospital,Conway Institute of Department ofRenal Medicine,Democritus University of
Biomolecular and Biomedical Research,University College Thrace,University Hospital,Alexandroupolis,Greece
Dublin;Dublin Molecular Medicine Centre,Dublin,Ireland
Flavio Vincenti,M.D.
Mark J.Sarnak,MD Professor ofClinical Medicine,Kidney Transplant Service,
Associate Director,Research Training Program,and Assistant Department ofMedicine,University ofCalifornia,San
Professor,Division ofNephrology,Department ofMedicine, Francisco,School ofMedicine,San Francisco,California
Tufts University School ofMedicine;Tufts-New England
Medical Center,Boston,Massachusetts Bradley A.Warady,M.D.
Professor ofPediatrics,University ofMissouri-Kansas City
Robert C.Stanton,M.D. School ofMedicine;Associate Chair ofPediatrics,Chief,
Assistant Professor in Medicine,Harvard Medical School; Section ofPediatric Nephrology;Director,Dialysis and
Chief,Nephrology Section,Joslin Diabetes Center,Boston, Transplantation;The Children’s Mercy Hospital,Kansas City,
Massachusetts Missouri
Rita Suri,M.D.,F.R.C.P.C. Daniel E.Weiner,M.D.,M.S.
StaffNephrologist,London Health Sciences Centre and Division ofNephrology,Department ofMedicine,Tufts-New
Assistant Professor ofMedicine,University ofWestern England Medical Center,Boston,Massachusetts
Ontario,London,Canada
Mark E.Williams,M.D.,F.A.C.P.
Cheuk-Chun Szeto,M.D.,M.R.C.P. Associate Clinical Professor in Medicine,Harvard Medical
Department ofMedicine & Therapeutics,Prince ofWales School;Nephrology Section,Joslin Diabetes Center,Boston,
Hospital,Shatin,Hong Kong Massachusetts
Geoffrey S.Teehan,M.D.,M.S. Jane Y.Yeun,M.D.
Division ofNephrology,Department ofMedicine,Tufts-New Associate Professor,Director,Nephrology Fellowship
England Medical Center,Boston,Massachusetts Program,University ofCalifornia Davis Health Center,
Department ofMedicine,Sacramento,California;Staff
Elias D.Thodis,M.D. Nephrologist,Sacramento Veterans Administration Medical
Assistant Professor ofNephrology,Demokritus University of Center,Department ofMedicine,Mather,California
Thrace,Alexandroupolis,Greece
xiii
Preface
For the past two decades,The Kidney,by Drs.Barry M.Brenner lines and clinical performance measures.These developments
and Floyd Rector,has been the central resource for authorita- have mandated a new look at the management of the patient
tive and current information in the field of nephrology. with CKD. Consequently, we invited distinguished scientists
However, the continuing expansion in the understanding of and educators in the field ofkidney disease to provide an in-
the pathophysiology and management ofkidney diseases,dial- depth review—from the laboratory to the clinic.Each author
ysis,and transplantation and rapid advances in technology led was challenged to discuss the fundamental concepts behind
to the need for more focused accompaniments to The Kidney. the management ofthe patient with ESRD,to provide a com-
Consequently,a series of companion textbooks emerged; the prehensive critique of clinical trials, and to present rational
first edition ofour textbook,Dialysis and Transplantation,was recommendations for clinical treatment.
the second in this series.The intent of our initial venture was Our strategy was to cover the most clinically relevant issues
to provide readers with a seamless flow ofinformation regard- in dialysis and transplantation and to classify them under the
ing the management ofthe patient with end-stage renal disease broad sections ofCKD,complications ofCKD,hemodialysis,
(ESRD),including hemodialysis,peritoneal dialysis,and trans- peritoneal dialysis, transplantation, acute renal failure, and
plantation. In pursuit of this goal, we sought to provide an economic issues.Each section was overseen by a section edi-
overview ofthe principles ofmanagement ofthe patient with tor. Each chapter is self-contained and provides the reader
ESRD as well as a more focused examination ofthe physiologic with a thorough review of the subject along with a complete
principles and clinical application of the different modes of list of key references. Diagnostic and treatment algorithms
kidney replacement therapy. have been used whenever possible.With an eye on the future,
Since the release of the first edition of our textbook,there our contributors were encouraged to identify major unan-
have been tremendous advances in the field ofkidney disease. swered questions,to suggest future clinical trials,and to high-
The publication of the National Kidney Foundation Kidney light promising experimental strategies. We have applied a
Disease Outcomes Quality Initiative (NKF KDOQI) guide- strong editorial policy to ensure that chapters remain bal-
lines has led to a new nomenclature and staging of patients anced and that they conform to these principles.The editorial
with chronic kidney disease (CKD) and has focused the team has changed; Dr William Owen has departed and Dr.
nephrology community on the magnitude of the problem. Peter G.Blake has joined us.In addition,we have had the priv-
Since most of the comorbidity and complications of CKD ilege of working with an extraordinary team of section edi-
begin early in the course of the disease, we have chosen to tors,Drs.Bertrand L.Jaber,V.S.Balakrishnan,Annamaria T.
expand the scope of this textbook to include the entire spec- Kausz,and Colm Magee,who have brought additional rigor
trum ofCKD,including the period prior to dialysis or trans- and vitality to the process
plantation. Hence the new title, Chronic Kidney Disease, In summary,we endeavored to significantly revise the first
Dialysis,and Transplantation.We undertook this revision with edition of out textbook, Dialysis and Transplantation, and
the understanding that the treatment ofpatients with ESRD is substantially expanded the scope in this edition, Chronic
complex,and the field is rapidly changing.The past few years Kidney Disease, Dialysis, and Transplantation. Readers are
have witnessed new frontiers in the understanding of the encouraged to refer to The Kidneyor other companions in this
pathophysiology,prevalence,and possible interventions with series for a detailed discussion of other issues in nephrology.
respect to cardiovascular disease, other comorbidity, and We intend to maintain this textbook as a work in progress and
complications of CKD.Likewise,there has been considerable to update it periodically as the relentless advances in the field
progress in the study ofthe physiologic basis ofdialysis and its mandate. During the coming years, we welcome comments,
complications and the immunologic basis of allograft toler- critiques, and suggestions from our readers as we strive to
ance and rejection. Advances in pharmaceutical technology deliver a comprehensive and contemporary textbook on dial-
and biotechnology have brought new and effective therapies ysis and transplantation.
into clinical use,and the results of several pivotal clinical tri-
als have challenged established concepts in patient manage- Brian J.G.Pereira
ment.Finally,the continuing efforts of professional societies Mohamed H.Sayegh
to improve the quality of patient care have resulted in the Peter G.Blake
development of new evidence-based clinical practice guide- EDITORS
SECTION AA
1
Chronic Kidney Disease
Chapter 1
Chronic Kidney Disease: Definition
and Epidemiology
Joseph A. Eustace, M.B., M.H.S., M.R.C.P.I.
●
Josef Coresh, M.D., Ph.D.
The developed world is suffering from an epidemic of kidney the increased mortality risk is the result ofCKD and that some
disease, the full spectrum of which is only beginning to be ofthis attributable risk is amenable to intervention.
understood. Figure 1–1 illustrates the “pyramid” of chronic In recognition of the current health crisis associated with
kidney disease (CKD), including estimates of the number of kidney failure,with its ever increasing prevalence,morbidity,
individuals at each stage in the United States.Kidney failure is mortality,and great cost ($20 billion for the U.S.ESRD pro-
the most visible aspect ofthis spectrum,but it represents only a gram in 2000), the most recent U.S. Public Health strategy,
minority of the total population affected by kidney disease.In “Healthy People,2010,”has for the first time devoted a sepa-
the United States the age,race,and gender adjusted incidence of rate chapter to CKD. Unfortunately, despite the evident
kidney failure requiring maintenance renal replacement ther- importance ofCKD we have very limited data on its epidemi-
apy (that is, who have end-stage renal disease, ESRD) has ology within the general population. Renal failure registry
increased over threefold in the last two decades,to a current rate data is unlikely to be representative of the broader spectrum
of 334 persons per million population (pmp).1 Although the of CKD,while clinical reports,by necessity,emphasize forms
annual rate ofincrease in the incidence rate has slowed to less ofkidney disease that more readily come to clinical attention.
than 1% for the last 2 years,given the expected demographic The epidemiology of CKD is, therefore, incompletely
trends in the general population,by 2030 there are projected to described and much ofthe available data is not generalizable.
be 2.2 million Americans who will require maintenance dialysis What is known is that there is a wide degree ofvariability both
or kidney transplantation.1 Similar trends, though of lesser within and between countries in the occurrence,clinical char-
magnitude,have been reported worldwide.In different national acteristics,and outcomes of patients with kidney failure and
registries the rate of increase in incidence has uniformly been that there has been substantial changes in these parameters
highest in the elderly.The U.S.race and gender adjusted inci- over time.
dence rates in subjects older than 75 years is 100-fold higher
than those ofindividuals younger than 20 years,while globally
the burden ofkidney disease is disproportionately borne by the
DEFINITION OF CHRONIC KIDNEY
socially disadvantaged and by racial minorities.1
DISEASE
In addition to those patients with ESRD,at least 8.0 million
Americans were estimated to have moderately or severely
Terminology
decreased kidney function,CKD stages III–IV.2 The extent to
which changes in the prevalence ofCKD parallel the increase in Investigation of the epidemiology of CKD has to date been
ESRD over the last decade is unknown.The presence ofCKD is hampered by the lack ofa uniform terminology.Traditionally,
clinically important, not only because such patients are at a wide and confusing combination ofexpressions,in English,
increased risk ofprogressing to kidney failure,but also because Latin, and ancient Greek, have been used interchangeably
CKD is independently associated with complications that are to describe a persistent decrement in kidney function.3 To
likely to directly contribute to poor health-related outcomes, help introduce a uniform terminology the National Kidney
the most important ofwhich is increased cardiovascular disease Foundation (NKF) in its Kidney Disease Outcomes Quality
morbidity and mortality.As a result,a person over age 65 with Initiative (KDOQI) has recently proposed a formal definition
severe CKD is several times more likely to die than to progress for CKD (Table 1–1).2 This definition provides a necessary
to requiring dialysis.1Increasing evidence suggests that some of and essential foundation to help standardize current medical
2 Chronic KKidney DDisease
Glomerular FFigure 11–1 The spectrum of chronic kidney
Stage
Filtration Rate, disease in the United States. *From USRDS
ml/min/1.73m2 (1988), includes approximately 230,000
Kidney <15 patients treated by dialysis, and assuming
5 Failure 70,000 additional patients not on dialysis.
(300,000) Other estimates are from NHANES III
(1988–1994): 15,600 individuals repre-
Severely Decreased 15–29 senting a U.S. population of 177 million
4
Filtration (400,000) age greater than age 20. Percentages total
to greater than 100% because NHANES III
may not have included dialysis patients.
GFR estimated from serum creatinine using
3 Moderately Decreased 30–59
Filtration (8 million) MDRD Study equation based on age, gen-
der, race, and calibration for serum creati-
nine. For Stages 1 and 2, CKD is based on
60–89 the persistence of positive spot albumin-to-
2 Kidney Damage with
Mildly Decreased Filtration (5 million) creatinine ratio greater than or equal to 17
mg/g in men or greater than or equal to 25
mg/g in women. Persistence of microalbu-
1 Kidney Damage with Normal Filtration (6 million) Normal minuria estimates are based on a subsample
(54% of those with GFR>90, N= 102; 73%
~120 of those with GFR 60–90, N= 44).
Table 11–1 Definition of Chronic Kidney Disease Table 11–2 Stages of Chronic Kidney Disease
1. Kidney damage for ≥3 months, as defined by structural GFR
or functional abnormalities of the kidney, with or without Stage Description (mL/min/1.73 mm2)
decreased GFR, manifest by either: 1 Kidney damage with normal ≥90
● Pathological abnormalities; or or ↑GFR
● Markers of kidney damage, including abnormalities
2 Kidney damage with 60–89
in the composition of the blood or urine, or abnormal- mild ↓GFR
ities in imaging tests 3 Moderate ↓GFR 30–59
2. GFR <60 mL/min/1.73 m2for ≥3 months, with or with- 4 Severe ↓GFR 15–29
out kidney damage
5 Kidney failure <15 (or dialysis)
(From the National Kidney Foundation KD: Clinical Practice
Chronic kidney disease is defined as either kidney damage or GFR
Guidelines for Chronic Kidney Disease: Evaluation, Classification, <60 mL/min/1.73 m2for ≥3 months. Kidney damage is defined as
and Stratification. Am J Kidney Dis 2002; 39 (suppl 1):S1-S266.
pathologic abnormalities or markers of damage, including abnor-
Copyright 2002, with permission from the National Kidney
malities in blood or urine tests or imaging studies. (From the National
Foundation.)
Kidney Foundation KD: Clinical Practice Guidelines for Chronic
Kidney Disease: Evaluation, Classification, and Stratification. Am
J Kidney Dis 2002; 39 (suppl 1): S1-S266. Copyright 2002, with
permission from the National Kidney Foundation.)
communication as well as to help make such communication
more readily intelligible to the patient.It further serves to help
identify and focus formal research in areas where it has tradi-
tionally been lacking, to facilitate appropriate population-
based screening,and to encourage the timely prevention and “renal”in this setting.We use the term azotemiato mean the
treatment ofkidney disease,as well as support formal quality overall toxicity state that accumulates with kidney dysfunc-
improvement initiatives. tion, without any implication at the overall severity of this
The NKF guidelines support the uniform use ofthe expres- state, and uremia to refer to the constellation of frequently
sion “chronic kidney disease”(CKD) to represent the entire subjective complications that develop with advanced azotemia
spectrum ofdisease that occurs following the initiation ofkid- and which necessitate the initiation ofrenal replacement ther-
ney damage.The severity ofthe resulting syndrome is denoted apy.Because the expression “end-stage renal disease”(ESRD)
by a staging scheme that extends from occult kidney damage, is widely used in regulatory and administrative circles,and it
with well-preserved function (stage I) down to the level of is codified in U.S.law,the KDOQI guidelines continue to use
kidney failure requiring renal replacement therapy (stage V) this expression to represent those subjects receiving or eligible
(Table 1–2).As the English word kidneylacks a ready adjecti- for renal replacement therapy either by some form ofdialysis
val form,in this chapter we will continue to use the expression or by transplantation.