Table Of ContentKIDNEY TRANSPLANTATION
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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
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broaden our understanding, changes in research methods, professional practices, or medical treatment
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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
