Handbook of Kidney TransplantationDanavitch ( 4E)

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1、 Edited byGABRIEL M. DANOVITCH MDMedical DirectorKidney Transplant Program, UCLA Medical Center; Professor, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSecondary EditorsLisa McAllisterAcquisitions EditorJoanne BersinDevelopmental EditorMelanie BennittProdu

2、ction SuperviserJoanne BowserProduction EditorBen RiveraManufacturing ManagerPatricia GastCover IllustrationCompositor: TechBooksPrinter: R.R. DonnelleyCrawfordsvilleContributing AuthorsSamhar I. Al-Akash M.D.Consultant PhysicianDivision of Pediatric Nephrology, King Faisal Specialist Hospital, Riya

3、dh, Saudi ArabiaWilliam J. C. Amend Jr. M.D.Attending PhysicianDepartment of Medicine, University of CaliforniaMoffitt/Long; Professor of Clinical Medicine, Department of Medicine, Kidney Transplant Service, University of California at San Francisco, San Francisco, CaliforniaSuphamai Bunnapradist M.

4、D.DirectorNephrology Fellowship Training Program; Medical Director, Kidney-Pancreas Transplant Program, Cedars-Sinai Medical Center; Assistant Professor, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaJ. Michael Cecka Ph.D.Director of Clinical ResearchUCLA Im

5、munogenetics Center, UCLA Medical Center; Professor, Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaArthur H. Cohen M.D.DirectorAnatomic Pathology, Department of Pathology, Cedars-Sinai Medical Center; Professor, Department of Pathology and Medicine, David G

6、effen School of Medicine at UCLA, Los Angeles, CaliforniaGabriel M. Danovitch M.D.Medical DirectorKidney Transplant Program, UCLA Medical Center; Professor of Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaRobert B. Ettenger M.D.ProfessorDepartment

7、of Pediatrics, Head, Department of Pediatric Nephrology, and Vice Chairman, Clinical Affairs, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaFabrizio Fabrizi M.D.Staff NephrologistDivision of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Milano, ItalyRobert S. Gaston M.D.Medica

8、l Director of Kidney and Pancreas TransplantationUniversity Hospital; Professor of Medicine and Surgery, School of Medicine, Division of Nephrology, University of Alabama at Birmingham, Birmingham, AlabamaMarci H. Gitlin M.S.W., L.C.S.W.Clinical Social WorkerUCLA Medical Center; Adjunct Professor, D

9、epartment of Social Welfare, UCLA, Los Angeles, CaliforniaWilliam G. Goodman M.D.Associate DirectorGeneral Clinical Research Center, UCLA Medical Center; Professor, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaH. Albin Gritsch M.D.Surgical DirectorDepartmen

10、t of Urology, Renal Transplant Program, UCLA Medical Center; Associate Professor, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaSusan Weil Guichard R.D., C.S.R.Renal DietitianUCLA Kidney and Pancreas Transplant Program, UCLA DaVita Dialysis Center, UCLA Medical Center, Los Angeles,

11、 CaliforniaSundaram Hariharan M.D.ChiefDivision of Nephrology, Department of Medicine, Froedtert Memorial Lutheran Hospital; Professor of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, WisconsinAndy Hwang Pharm.D.Research AssociateDepartment of Medicine, David Geffen Scho

12、ol of Medicine at UCLA, Los Angeles, CaliforniaBertram L. Kasiske M.D.DirectorDivision of Nephrology, Hennepin County Medical Center; Professor, Department of Medicine, University of Minnesota, Minneapolis, MinnesotaElizabeth A. Kendrick M.D.Assistant Clinical Professor of MedicineDivision of Nephro

13、logy, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaBernard M. Kubak M.D., Ph.D.Associate Professor of Infectious Disease/MedicineDivision of Infectious Disease, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaDidier A. Mandelbrot M.D.Staff NephrologistDepartment of

14、 Medicine, UMass Memorial Hospital; Associate Professor, Department of Medicine, University of Massachusetts, Worcester, MassachusettsCynthia L. Maree M.D.Senior Clinical FellowDivision of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaPaul Martin M.D.Clinical a

15、nd Medical DirectorCenter for Liver and Kidney Disease and Transplantation, Cedars-Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaKirk J. Murphy M.D.Attending PsychiatristDepartment of Psychiatry, UCLA Medical Center; Assistant Clinical P

16、rofessor, Department of Psychiatry, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaCynthia C. Nast M.D.Attending PathologistDepartment of Pathology, Cedars-Sinai Medical Center; Professor of Pathology, Department of Pathology, David Geffen School of Medic

17、ine at UCLA, Los Angeles, CaliforniaDavid A. Pegues M.D.EpidemiologistDepartment of Infectious Diseases, UCLA Medical Center; Professor of Clinical Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaJohn D. Pirsch M.D.Director of Medical Transp

18、lant ServiceDepartment of Medicine and Surgery, University of Wisconsin Hospital and Clinic; Professor, Department of Medicine and Surgery, University of Wisconsin Medical School, Madison, WisconsinNagesh Ragavendra M.D.ChiefUltrasound Section, UCLA Medical Center; Clinical Professor of Radiology, D

19、epartment of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaElaine F. Reed Ph.D.DirectorUCLA Immunogenetics Center; Professor, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaJ. Thomas Rosenthal M.D.Professo

20、rDepartment of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaMeena Sahadevan M.D.Staff NephrologistDivision of Nephrology, Hennepin County Medical Center; Assistant Professor, Department of Medicine, University of Minnesota, Minneapolis, MinnesotaMohamed H. Sayegh M.D.Rese

21、arch DirectorDepartment of Immunogenetics and Transplantation, Brigham & Womens Hospital; Associate Professor, Department of Medicine, Harvard Medical School, Boston, MassachusettsChristiaan Schiepers M.D. Ph.D.Department of Nuclear Medicine, UCLA Medical Center; Professor, Department of Molecular a

22、nd Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CaliforniaRobyn S. Shapiro J.D.Partner and ChairHealth Law Group, Michael Best & Freidrich, L.L.P; Ursula von Der Ruhr Professor and Director, Center for the Study of Bioethics, Medical College of Wisconsin, Milwaukee, Wi

23、sconsinNauman Siddqi M.D.Faculty PhysicianDepartment of Medicine, Froedtert Memorial Lutheran Hospital; Assistant Professor of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, WisconsinJennifer Singer M.D.Assistant ProfessorDepartment of Urology, David Geffen School of Medi

24、cine at UCLA, Los Angeles, CaliforniaCraig Smith M.D.Associate ProfessorDepartment of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, California; Associate Professor, Department of Surgery and Urology, David Geffen School of Medicine at UCLA, Los Angeles, Calif

25、orniaHans W. Sollinger M.D., Ph.D.ChairmanDivision of Organ Transplantation, Department of Surgery, University of Wisconsin Hospital; Folkert O. Belzer Professor of Surgery, Chairman, Division of Organ Transplantation, Department of Surgery, University of Wisconsin Medical School, Madison, Wisconsin

26、Stephen J. Tomlanovich M.D.Medical DirectorKidney Transplant Service, Department of Medicine and Surgery, University of California at San Francisco Medical Center; Clinical Professor, Department of Medicine and Surgery, University of California at San Francisco, San Francisco, CaliforniaFlavio Vince

27、nti M.D.Clinical ProfessorDepartment of Medicine, University of California at San Francisco, San Francisco, CaliforniaPeter Zimmerman M.D.Associate ProfessorDepartment of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, California DedicationIn honor of my mother, Gertrude Danovitch,

28、who remains, in her later years, a source of inspiration to three generations of loving progeny.PrefaceThe publication of the fourth edition of the Handbook of Kidney Transplantation coincides with the fiftieth anniversary of two critical milestones in the history of modern medicine. The modern era

29、of transplant immunology can be said to have begun with the description of actively acquired immunologic tolerance in rats by Peter Medawar and his colleagues at University College, London in 1953, while the modern era of clinical transplantation began on December 23, 1954, when Joseph Murray and hi

30、s colleagues at Harvard performed the first kidney transplantation between identical twin brothers. Both these pioneers were rewarded with the Nobel Prize for their contributions.In many ways, the promise of these momentous events has been fulfilled in the half century that has followed. The mere fa

31、ct that organ transplantation is the subject of a handbook such as this reflects the extent to which it has become normative medical practice. Hundreds of thousands of lives have been saved and quality years have replaced years of suffering. Our understanding of the complex immunobiology of the immu

32、ne response has advanced and has brought widespread benefits well beyond the field of organ transplantation. A broad armamentarium of immunosuppressive medications is now available, and innovative surgical techniques serve to expand the donor pool and minimize morbidity. National and international o

33、rgan-sharing organizations are an accepted part of the medical landscape.Modern organ transplantation can be visualized as a complex edifice that rests on a triangular base. In one corner is the basic research that is the life-blood of improvement and innovation. Nowhere in medicine is the term “tra

34、nslational medicine” more relevant or does research reach the bedside with greater speed. In another corner is clinical transplant medicine, a new medical subspecialty that requires compulsive, detail-oriented clinical care, and both organ-specific and broad expertise. In the third corner are the et

35、hical underpinnings of the whole transplant endeavor, an endeavor that is utterly dependent on human altruism and love, and an absolute trust among medical staff, patients, and families that is the bedrock of societal acceptance of organ donation, from both the living and the deceased.The edifice is

36、 strong, but its strength cannot be taken for granted. The immune system still has many secrets it has yet to reveal. As this text describes, the ultimate goal of donor-specific tolerance, either complete or near complete, appears closer than ever. Clinical xenotransplantation, however, a procedure

37、that could provide the ultimate answer to the organ donor shortage, remains remote. The availability of new immunosuppressive agents has permitted the introduction of innovative immunosuppressive regimens designed to minimize toxicity. Yet the success of clinical transplantationwith low mortality, h

38、igh graft survival, and a low incidence of rejection episodeshas, paradoxically, made it more difficult to prove the benefit of new approaches. Because the demand for organs greatly outstretches supply, patients with advanced kidney disease who do not have a living donor may be faced with an intermi

39、nable, and often morbid, wait for an organ from a deceased donor. The need for living donors has, on the one hand, provided a stimulus to develop ingenious new techniques and approaches to facilitate donation, and on the other hand, has spawned an illegal global market in purchased organs.The 4-year

40、 intervals between the publication of each of the editions of the Handbook of Kidney Transplantation are a reflection of the rate of change in the world of organ transplantation. This fourth edition has been thoroughly updated and revised to reflect the most current knowledge and practice in the fie

41、ld. Like its predecessors, its mission is to make the clinical practice of kidney transplantation fully accessible to all those who are entrusted with the care of our long-suffering patients.Gabriel M. Danovitch1Options for Patients with Kidney FailureWilliam G. GoodmanGabriel M. DanovitchBefore 197

42、0, therapeutic options for patients with kidney failure were quite limited. Only a small number of patients received regular dialysis because few dialysis facilities had been established. Patients underwent extensive medical screening to determine their eligibility for ongoing therapy, and treatment

43、 was offered only to patients who had renal failure as the predominant clinical management issue. Patients with other systemic illnesses apart from kidney failure were not considered for chronic dialysis therapy. Kidney transplantation was in the early stages of development as a viable therapeutic o

44、ption. Transplant immunology and immunosuppressive therapy were in their infancy, and for most patients, a diagnosis of chronic renal failure was a death sentence.In the decade that followed, the availability of care for patients with kidney failure grew rapidly throughout the medically developed wo

45、rld. In the United States, the passage of Medicare entitlement legislation, in 1972, to pay for maintenance dialysis and renal transplantation, provided the major stimulus for this expansion. This trend continues unabated, at least for hemodialysis.Despite numerous medical and technical advances, pa

46、tients with kidney failure who are treated with dialysis often remain unwell. Constitutional symptoms of fatigue and malaise persist despite better management of anemia with erythropoietin. Progressive cardiovascular disease (CVD), peripheral and autonomic neuropathy, bone disease, and sexual dysfun

47、ction are common, even in patients who are judged, using established, objective criteria, to be treated adequately with dialysis. Patients may become dependent on family members or others for physical, emotional, and financial assistance. Rehabilitation, particularly vocational rehabilitation, remai

48、ns poor. Such findings are not unexpected, however, because the most efficient hemodialysis regimens currently provide only 10% to 12% of the small-solute removal of two normally functioning kidneys. Removal of higher-molecular-weight solutes is even less efficient.For most patients with kidney fail

49、ure, kidney transplantation has the greatest potential for restoring a healthy, productive life. Renal transplantation does not, however, occur in a clinical vacuum. Virtually all transplant recipients have been exposed, at least to some extent, to the adverse consequences of chronic kidney disease

50、(CKD). Practitioners of kidney transplantation must consider the clinical impact of CKD on the overall health of renal transplantation candidates when this therapeutic option is first considered. They must also remain cognizant of the potential long-term consequences of previous and current CKD (see

51、 Chapter 6) during what may be decades of clinical follow-up after successful renal transplantation (see Chapter 9).STAGES OF CHRONIC KIDNEY DISEASETable 1.1 summarizes the stages of CKD as defined by the National Kidney Foundation Disease Outcome Quality Initiative (K/DOQI). The purpose of this cla

52、ssification is to permit more accurate assessments of the frequency and severity of CKD in the general population, enabling more effective targeting of treatment recommendations. Note that the classification is based on estimated values for glomerular filtration rate (GFR) and that the terms kidney

53、failure or end-stage renal disease (ESRD) are used for patients with values less than 15 mL per minute. It has been estimated that close to 20 million adults in the United States have CKD that can be categorized as stage 1, 2, 3, or 4, whereas approximately 300,000 have overt kidney failure, or stag

54、e 5 CKD. The known population of patients with ESRD thus represents only the “tip of the iceberg” of progressive CKD. It is also evident from Table 1.1 that most, if not all, kidney transplant recipients can be regarded as having some degree of CKD because their kidney function is rarely normal.Tabl

55、e 1.1. Stages of chronic kidney disease (CKD)StageDescriptionGFR (mL/min/1.73m2)1Kidney damage with normal or increased GFR902Kidney damage with mild decrease in GFR60903Moderate decrease in GFR30594Severe decrease in GFR15295Kidney failure15 or dialysisGFR, glomerular filtration rate.A discussion o

56、f the management of CKD in the general population is beyond the scope of this text. Strict blood pressure control and the use of angiotensin-converting enzyme inhibitors, both in diabetic patients and in those with proteinuria from other glomerular diseases, are standard practice. There is less cert

57、ainty, however, about the benefits of these agents in patients without significant proteinuria. Low-protein diets may delay the onset of kidney failure or death in patients with established CKD, but there is insufficient evidence to recommend restricting dietary protein intake to less than 0.8 g/kg

58、per day on a routine basis. Lipid-lowering agents and lifestyle changes, particularly smoking cessation, may slow disease progression. Many of the concerns and treatment recommendations that pertain to the long-term management of kidney transplant recipients, which are discussed in Chapter 9, also a

59、pply to patients with CKD.Estimation of Glomerular Filtration RateMeasurements of GFR provide an overall assessment of kidney function both in the transplant and nontransplant settings. The GFR is measured best by the clearance of an ideal filtration marker such as inulin or with radiolabelled filtr

60、ation markers (see Chapter 12). In clinical practice, GFR is usually estimated from measurements of creatinine clearance or serum creatinine levels to circumvent the need for timed urine specimen collections. Several equations have been developed to estimate GFR after accounting for variations in ag

61、e, sex, body weight, and race. The most popular and easiest to use among these is the Cockcroft-Gault formulaThe MDRD (Modification of Diet in Renal Disease) equation uses a formula based on serum creatinine, age, gender, and race. It should be noted that neither equation has been formally validated

62、 in renal transplant recipients.DEMOGRAPHICS OF THE END-STAGE RENAL DISEASE POPULATIONUnited StatesEach year, the United States Renal Data System (USRDS) provides updated demographic information about patients with kidney disease who are treated either with dialysis or renal transplantation in the U

63、nited States. The 2002 report is based on data updated through March 2002 that are complete only through December 2000. At that time, 275,000 patients were receiving maintenance dialysis in the United States (Table 1.2). This number continues to increase at an annual rate of approximately 5%. By the

64、 year 2010, it is expected to reach 520,000. The average age of the dialysis population also continues to increase each year. Nearly half of patients undergoing regular dialysis are older than 65 years of age, and the mean age of those beginning treatment is greater than 60 years. This phenomenon has been described as the “gerontologizing” of nephrology, and it accounts for the increasing age of patients being evaluated for, awaiting