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KIDNEY TRANSPLANTATION Executive Content Strategist: Michael Houston Content Development Specialists: Rachael Harrison and Alexandra Mortimer Project Manager: Sukanthi Sukumar Designer: Christian Bilbow Illustration Manager: Jennifer Rose Illustrator: Antbits Ltd Marketing Manager: Abigail Swartz KIDNEY TRANSPLANTATION: PRINCIPLES AND PRACTICE SEVENTH EDITION Sir Peter J. Morris, MD, PhD, FRS, FRCS Emeritus Nuffield Professor of Surgery, University of Oxford; Honorary Professor, University of London; Director, Centre for Evidence in Transplantation, Royal College of Surgeons of England, London, UK Stuart J. Knechtle, MD, FACS Clinical Director; Professor of Surgery and Pediatrics; Mason Chair of Transplant Surgery, Emory Transplant Center, Atlanta, GA, USA Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2014 © 2014, Elsevier Inc. All rights reserved. First edition 1979 Second edition 1984 Third edition 1988 Fourth edition 1994 Fifth edition 2001 Sixth edition 2008 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/ permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. A catalogue record for this book is held in the British Library. ISBN: 9781455740963 Ebook ISBN: 9781455774050 Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 V T C ideo able of onTenTs Access all videos online at expertconsult.com. See inside front cover for activation code. Ch 02 clip 01 Formation of an immune synapse Ch 06 clip 01 Brain Death Examination Dan Davis Laura S. Johnson Nicholas Byron Pitts Ch 02 clip 02 3-D rotational image of immune synapses Ram M. Subramanian Fiona J. Culley Ch08 clip 01 Laparoendoscopic single site (LESS) Ch 02 clip 03 An NK cell killing its target donor nephrectomy: technique and outcomes Dan Davis Rolf N. Barth Ch 05 clip 01 Laparoscopic: Peritoneal Dialysis - Ch 42 clip 01 The Transplant Library on OvidSP Catheter Insertion Techniques Adam D. Barlow Ch 42 clip 02 The Transplant Library on Evidentia James P. Hunter Liset H.M. Pengel Michael L. Nicholson vii P f e reface to the irst dition Renal transplantation is now an accepted treatment of future it may be possible to work out a satisfactory way of patients in end-stage renal failure. A successful trans- determining the reaction of the recipient’s blood serum or plant restores not merely life but an acceptable quality tissues to those of the donor and the reverse; perhaps in this of life to such patients. The number of patients in end- way we can obtain more light on this as yet relatively dark stage renal failure in the Western World who might be side of biology. treated by hemodialysis and transplantation is consider- able and comprises some 30-50 new patients/million of The recognition that allogeneic tissues would be re- population. Unfortunately in most, if not all, countries jected was further established in later years by Drs. Gibson the supply of kidneys for transplantation is insufficient and Medawar, who treated burn patients with homografts to meet the demand. Furthermore, hemodialysis facili- in Glasgow during the Second World War. Indeed, it was ties are usually inadequate to make up this deficit so that the crash of a bomber behind the Medawars’ house in many patients are still dying of renal disease who could Oxford during the early years of the war that first stimu- be restored to a useful and productive life. Nevertheless, lated his interest in transplantation, especially of skin. few of us would have imagined even 10 years ago that In his address at the opening of the new Oxford transplantation of the kidney would have become such a Transplant Unit in 1977, Sir Peter Medawar recounted relatively common procedure as is the case today, and in- this event. deed well over 30,000 kidney transplantations have been performed throughout the world. Early in the war, an R.A.F. Whitley bomber crashed into Transplantation of the kidney for the treatment of re- a house in North Oxford with much serious injury and loss nal failure has been an attractive concept for many years. of life. Among the injured was a young man with a third As long ago as 1945, three young surgeons at the Peter degree burn extending over about 60% of his body. People Bent Brigham Hospital in Boston, Charles Hufnagel, burned as severely as this never raised a medical problem Ernest Landsteiner and David Hume, joined the ves- before: they always died; but the blood transfusion services sels of a cadaver kidney to the brachial vessels of a young and the control of infection made possible by the topical use woman who was comatose from acute renal failure due to of sulphonamide drugs now made it possible for them to stay septicemia. The kidney functioned for several days before alive. Dr. John F. Barnes, a colleague of mine in Professor it was removed, and the woman regained consciousness. H. W. Florey’s School of Pathology, asked me to see this Shortly afterwards, the woman’s own kidneys began to patient in the hope that being an experimental biologist function and she made a full recovery. The advent of the I might have some ideas for treatment. With more than artificial kidney at that time meant that this approach to half his body surface quite raw, this poor young man was a the treatment of acute renal failure was no longer nec- deeply shocking sight; I thought of and tried out a number essary, but attention was soon given to the possibility of of ingenious methods, none of which worked, for ekeing out transplanting kidneys to patients with end-stage renal his own skin for grafting, trying to make one piece of skin failure who were requiring dialysis on the newly devel- do the work of ten or more. The obvious solution was to use oped artificial kidney to stay alive. skin grafts from a relative or voluntary donor, but this was Although the first experimental kidney transplants in not possible then and it is not possible now. animals were reported first in Vienna by Dr. Emerich I believe I saw it as my metier to find out why it Ulmann in 1902 and then in 1905 by Dr. Alexis Carrel was not possible to graft skin from one human being to in the United States, the problem of rejection was not another, and what could be done about it. I accordingly mentioned by either author. Later in 1910, Carrel did began research on the subject with the Burns Unit of the discuss the possible differences between an autograft Glasgow Royal Infirmary, and subsequently in the Zoology and a homograft. The vascular techniques developed by Department in Oxford. If anybody had then told me that Carrel for the anastomosis of the renal vessels to the re- one day, in Oxford, kidneys would be transplanted from cipient vessels are still used today. But in 1923, Dr. Carl one human being to another, not as a perilous surgical Williamson of the Mayo Clinic clearly defined the dif- venture, but as something more in the common run of ference between an autografted and homografted kidney things, I should have dismissed it as science fiction; yet it and even published histological pictures of a rejecting is just this that has come about, thanks to the enterprise of kidney. Furthermore, he predicted the future use of tis- Professor Morris and his colleagues. sue matching in renal transplantation. Nevertheless in 1951, David Hume in Boston em- It is unfortunate that the lower animals, such as the dog, barked on a series of cadaver kidney transplants in which do not possess a blood grouping like that of man. In the the kidney was placed in the thigh of the recipient. All but ix x Preface to the first edition one of these kidneys were rejected within a matter of days of steroids, the standard immunosuppressive therapy of or weeks, the one exception being a patient in whom the today was introduced to the practice of renal transplanta- kidney functioned for nearly 6 months and enabled the tion in the early sixties. patient to leave the hospital! This event provided hope Not that this meant the solution of the problems of for the future as no immunosuppressive therapy had been renal transplantation for this combination of drugs was used in this patient. At this time, the problems of rejec- dangerous and mortality was high in those early years. tion of kidney allografts in the dog were being clearly But there was a significant number of long-term success- defined by Dr. Morton Simonsen in Copenhagen and ful transplants, and as experience grew, the results of renal Dr. William Dempster in London, but in 1953, a ma- transplantation improved. Another major area of en- jor boost to transplantation research was provided by the deavor in renal transplantation at that time was directed demonstration, by Drs. Rupert Billingham, Lesley Brent at the study of methods of matching donor and recipient and Peter Medawar, that tolerance to an allogeneic skin for histocompatibility antigens with the aim of lessening graft in an adult animal could be produced by injecting the immune response to the graft and so perhaps allow- the fetus with donor strain tissue, thus confirming ex- ing a decrease in the immunosuppressive drug therapy. perimentally the clonal selection hypothesis of Burnet Although this aim has only been achieved to any great ex- and Fenner in the recognition of self and non-self. The tent in siblings who are HLA identical, tissue typing has induction of specific unresponsiveness of a host to a tis- made a significant contribution to renal transplantation, sue allograft has remained the ultimate goal of transplant perhaps best illustrated by the recognition in the late six- immunologists ever since. ties that the performance of a transplant in the presence Then in 1954, the first kidney transplant between of donor-specific presensitization in the recipient leads to identical twins was carried out successfully at the Peter hyperacute or accelerated rejection of the graft in most Bent Brigham Hospital which led to a number of further instances. Nevertheless, the more recent description of successful identical twin transplants in Boston and else- the Ia-like system in man (HLA-DR) may have an impor- where in the world over the next few years. tant impact on tissue typing in renal transplantation. The There still remained the apparently almost insol- present decade also has seen an enormous effort directed uble problem of rejection of any kidney other than an at immunological monitoring in renal transplantation identical-twin kidney. The first attempts to suppress the and at attempts to induce experimental specific immuno- immune response to a kidney allograft employed total suppression. We have solved most of the technical prob- body irradiation of the recipient and were carried out by lems of renal transplantation; we have been left with the Dr. Merril’s group in Boston, two groups in Paris under problem of rejection and the complications arising from the direction of Drs. Kuss and Hamburger, respectively, the drug therapy given to prevent rejection. and by Professor Shackman’s group in London. Rejection Although the contributions in this book cover all as- of a graft could be suppressed by irradiation, but the com- pects of renal transplantation, certain subjects, as for plications of the irradiation were such that this was really example immunological monitoring before transplanta- an unacceptable approach, although an occasional rela- tion, transplantation in children and cancer after renal tively long-term acceptance of a graft provided encour- transplantation, have received considerable emphasis as agement for the future. they do represent developing areas of great interest, and I Then came the discovery by Drs. Schwartz and must take responsibility for this emphasis. For in the sev- Dameshek in 1959 that 6-mercaptopurine could suppress enties we have seen many of the principles and practice the immune response of rabbits to human serum albumin. of renal transplantation become established and the areas Shortly afterwards, they showed that the survival of skin of future investigation become more clearly defined. allografts in rabbits was significantly prolonged by the With an ever-increasing demand for renal transplanta- same drug. This event ushered in the present era of renal tion, more and more people in many different disciplines, transplantation, for very quickly Roy Calne in London doctors (surgeons, physicians, pathologists, virologists, and Charles Zukoski working with David Hume in immunologists), nurses, scientists and ancillary staff are Virginia showed that this same drug markedly prolonged becoming involved in renal transplantation either in the the survival of kidney allografts in dogs. And indeed, clinic or in the laboratory. It is to these people I hope this 6-mercaptopurine was first used in a patient in Boston in book will be of value. 1960. Elion and Hitchings of the Burroughs Wellcome Research Laboratories in New York State then developed Sir Peter J. Morris azathioprine, which quickly replaced 6-m ercaptopurine Oxford, UK in clinical practice as it was less toxic. With the addition November 1978 P S e reface to the eventh dition It is amazing, at least from our point to view, to realise and safe agent, perhaps discarded a little early, but as it that it is 35 years (1978) since the first edition of Kidney was the first immunosuppressive agent available way back Transplantation: Principles and Practice was published. in the 1960’s then if for no other reason than a historical In 1954, the first successful kidney transplant was per- one, it deserves a brief chapter. formed by the late Joseph Murray at the Peter Bent Patient and graft survival continued to improve in Brigham Hospital in Boston. Thus as we look back on the short and medium term and in most units good risk the first edition it certainly made us realise how far we patients can achieve one year graft survival of 90% or have come. Although at times people working in kidney better at one year, but the long term survival of kidney transplantation feel a little despondent that we are not grafts has not improved all that much despite the vari- making sufficient progress, progress, as always, continues ous new immunosuppressive agents. Chronic allograft to be made, which is certainly evident if you review the nephropathy remains a major problem. Again in the past six editions of this book. preservation area hypothermic machine preservation is In this edition we have a number of new authors and being revaluated with promising results now available have added some additional chapters. For example the and this is extensively discussed on the chapter on pres- new immunosuppressive agent that has appeared on the ervation. There is a separate chapter on steroids, but screen is Belatacept (a fusion protein which inhibits co now concentrating on steroid avoidance or sparing. For stimulation) and as there are a considerable number of the first time we have now an electronic edition in keep- well conducted randomised controlled trials of this new ing with changes in media presentation, and added video biological agent all showing considerable promise, we felt clips to more thoroughly illustrate the principles related it was worthy of a chapter by itself, at least in this edi- to our field. tion. We also have added a chapter on paired exchange Renal transplantation is an exciting area and we have programmes for living donors which has become wide- to be grateful to the scientists and clinicians that made the spread now throughout the world. Finally we have added current results possible and to the thousands of patients a chapter on evidence in transplantation where it be- who have participated in this evolution of renal trans- comes increasingly apparent that we do need to have a plantation over the last 50 years. better basis of evidence for what we do. The remaining chapters cover much the same topics as in the previous Sir Peter J. Morris editions but of course in many of those areas there have London, UK been considerable changes and so a lot of updating has been necessary. One might ask why we have a chapter Stuart Knechtle on azathioprine alone? This is really because it is a good Atlanta, GA, USA xi L C ist of ontributors Richard D.M. Allen, MBBS, FRACS Robert B. Colvin, MD Professor of Transplantation Surgery, University of Massachusetts General Hospital and Harvard Medical Sydney; Director of Transplantation Services, Royal School, Boston, MA, USA Prince Alfred Hospital, Sydney, Australia Ch 26 Pathology of Kidney Transplantation Ch 28 Vascular and Lymphatic Complications after Kidney Transplantation Lynn D. Cornell, MD Consultant, Division of Anatomic Pathology; Frederike Ambagtsheer, MSc, LLM Associate Professor of Laboratory Medicine and Scientific Researcher, Erasmus MC University Pathology, Mayo Clinic College of Medicine, Hospital, Department of Internal Medicine, Kidney Mayo Clinic, Rochester, MI, USA Transplantation Section, Rotterdam, The Netherlands Ch 26 Pathology of Kidney Transplantation Ch 41 Ethical and Legal Aspects of Kidney Donation Fiona J. Culley, PhD Amit Basu, MD, FACS, FRCS(Edin) National Heart and Lung Institute, Imperial College Attending Transplant Surgeon, Transplant Center, London, London, UK North Shore Long Island Jewish Health System, Ch 02 clip 02 3-D rotational image of immune synapses Manhasset, New York, USA Ch 17 Calcineurin Inhibitors Margaret J. Dallman, DPhil Professor of Immunology and Principal, Faculty of Simon Ball, MA, PhD, FRCP Natural Sciences, Department of Life Sciences, Consultant Nephrologist, Queen Elizabeth Hospital Imperial College London, London, UK Birmingham, Birmingham, UK Ch 02 Immunology of Graft Rejection Ch 02 Immunology of Graft Rejection Andrew Davenport, MD Adam D. Barlow, MBBS, MRCS, MD Consultant Renal Physician, UCL Centre for Specialist Registrar in Transplantation, Transplant Nephrology, Royal Free Hospital, London, UK Group, Department of Infection, Immunity and Ch 03 Chronic Kidney Failure: Renal Replacement Therapy Inflammation, University of Leicester, Leicester, UK Ch 05 Access for Renal Replacement Therapy; Dan Davis, PhD Ch 05 Clip 01 Laparoscopic: Peritoneal Dialysis - Catheter Department of Life Sciences, Imperial College London, Insertion Techniques London, UK Ch 02 clip 01 Formation of an immune synapse; Rolf N. Barth, MD Ch 02 clip 03 An NK cell killing its target Associate Professor of Surgery, Division of Transplantation, University of Maryland School of Alton B. Farris, III, MD Medicine, Baltimore, MD, USA Department of Pathology, Emory University Hospital, Ch 08 Donor Nephrectomy; Atlanta, GA, USA Ch 08 clip 01 Laparoendoscopic single site (LESS) donor Ch 26 Pathology of Kidney Transplantation nephrectomy: technique and outcomes Jay A. Fishman, MD J. Andrew Bradley, PhD, FRCS, FMedSci Profesor of Medicine; Director, Transplant Infectious Professor of Surgery, University of Cambridge; Disease and Compromised Host Program, Harvard Honorary Consultant Surgeon, Addenbrooke’s Medical School and Massachusetts General Hospital, Hospital, Cambridge, UK Boston, MA, USA Ch 19 mTor Inhibitors: Sirolimus and Everolimus Ch 31 Infection in Kidney Transplant Recipients Jeremy R. Chapman, MD, MB, BChir, FRACP, FRCP Andria L. Ford, MD, MSCI Clinical Professor of Renal Medicine, Centre for Assistant Professor in Neurology, Washington University Transplant and Renal Research, University of Sydney, in St. Louis School of Medicine; Attending Physician, Sydney, Australia; Westmead Hospital, Westmead, Barnes-Jewish Hospital, St. Louis, MO, USA Australia Ch 33 Neurological Complications after Kidney Ch 04 The Recipient of a Kidney Transplant Transplantation xiii xiv List of Contributors Julie Franc-Guimond, MD David Hamilton, PhD, FRCS Associate Professor, University of Montreal, Montreal, Honorary Senior Lecturer, Bute Medical School, St Quebec, Canada Andrews University, St Andrews, Scotland Ch 12 Transplantation and the Abnormal Bladder Ch 01 Kidney Transplantation: A History Patricia M. Franklin, MSc, BSc(Hons), RGN James P. Hunter, BSc(Hons), MBChB, MRCS Kidney Patient Advisor – Psychologist, Oxford Renal Senior Clinical Research Fellow, Transplant Medicine and Transplant Centre, The Churchill Group, Department of Infection, Immunity and Hospital, Oxford, UK Inflammation, University of Leicester, Leicester, UK Ch 40 Psychological Aspects of Kidney Transplantation and Ch 05 Access for Renal Replacement Therapy; Organ Donation Ch 05 Clip 01 Laparoscopic: Peritoneal Dialysis - Catheter Insertion Techniques Peter J. Friend, MA, MB, BCHIR, FRCS, MD Professor of Transplantation, University of Oxford; Alan G. Jardine, BSc, MD, FRCP Consultant Surgeon Oxford University NHS Trust Professor of Renal Medicine, University of Glasgow, Oxford Transplant Centre, Nuffield Department of Glasgow, Scotland Surgical Sciences, Oxford, UK Ch 30 Cardiovascular Disease in Renal Ch 9 Kidney Preservation; Transplantation Ch 11 Surgical Techniques of Kidney Transplantation Sasha Nicole Jenkins, MD, MPH Susan V. Fuggle, BSc(Hons), MSc, DPhil, FRCPath Emory Department of Dermatology Chief Resident, Reader in Transplant Immunology, University of Emory University, Department of Dermatology Oxford; Director of Clinical Transplant Immunology, Atlanta, GA, USA Transplant Immunology and Immunogenetics, Oxford Ch 34 Non-malignant and Malignant Skin Lesions in Transplant Centre, Churchill Hospital, Oxford, UK Kidney Transplant Patients Ch 10 Histocompatibility in Kidney Transplantation Juan Antonio Jiménez, MD, PhD Robert S. Gaston, MD Resident Physician, Glickman Urological and Kidney Robert G. Luke Chair in Transplant Nephrology; Institute, Cleveland Clinic Foundation, Cleveland, Medical Director of Kidney and Pancreas OH, USA Transplantation; Co-Director, Comprehensive Ch 29 Urological Complications after Kidney Transplantation Transplant Institute, University of Alabama at Birmingham, Birmingham, AL, USA Laura S. Johnson, MD Ch 18 Mycophenolates Department of Surgical Critical Care/Trauma/ Acute Care Surgery, Washington Hospital Center, Sommer E. Gentry, PhD Washington, DC, USA Associate Professor of Mathematics, Department Ch 06 Brain Death and Cardiac Death: Donor Criteria of Mathematics, United States Naval Academy, and Care of Deceased Donor; Annapolis, MD; Department of Surgery Johns Ch 06 clip 01 Brain Death Examination Hopkins University School of Medicine, Baltimore, MD, USA Allan D. Kirk, MD, PhD, FACS Ch 25 Kidney Paired Donation Programs for Living Professor of Surgery and Pediatrics, Emory University; Donors Scientific Director, Emory Transplant Center, Emory University Hospital, Atlanta, GA, USA Ricardo González, MD Ch 20 Antilymphocyte Globulin, Monoclonal Antibodies, Auf der Bult Youth and Children’s Hospital, and Fusion Proteins; Hannover Medical School, Hannover, Germany; Ch 21 Belatacept Charité University Medicine Berlin, Berlin, Germany Stuart J. Knechtle, MD, FACS Ch 12 Transplantation and the Abnormal Bladder Clinical Director; Professor of Surgery and Pediatrics; Mason Chair of Transplant Surgery, Emory Angelika C. Gruessner, MS, PhD Transplant Center, Atlanta, GA, USA Professor, Mel and Enid College of Public health, Ch 14 Early Course of the Patient with a Kidney Division of Epidemiology and Biostatistics, Transplantation; University of Arizona, Tucson, AZ, USA Ch 39 Results of Renal Transplantation Ch 36 Pancreas and Kidney Transplantation for Diabetic Nephropathy Simon R. Knight, MChir, MA, MB, FRCS Deputy Director, Centre for Evidence in Transplantation, Rainer W.G. Gruessner, MD Clinical Effectiveness Unit, Royal College of Surgeons Professor of Surgery and Immunobiology; Chair, of England, London, UK; Academic Clinical Lecturer Department of Surgery, University of Arizona College in Transplant Surgery, Nuffield Department of of Medicine, Tucson, AZ, USA Surgical Sciences, University of Oxford, Oxford, UK Ch 36 Pancreas and Kidney Transplantation for Diabetic Ch 16 Steroids; Nephropathy Ch 42 Evidence in Transplantation

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