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Cambridge University Press978-0-521-19753-3 - Organ Transplantation: A Clinical GuideEdited by Andrew A. Klein, Clive J. Lewis and Joren C. MadsenFrontmatterMore information

Organ TransplantationA Clinical Guide

http://www.cambridge.org/9780521197533

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Organ TransplantationA Clinical GuideEdited byAndrew A. KleinConsultant, Anaesthesia and Intensive Care, Papworth Hospital, Cambridge, UK

Clive J. LewisConsultant Cardiologist and Transplant Physician, Papworth Hospital, Cambridge, UK

Joren C. MadsenDirector of the MGH Transplant Center, Section Chief for Cardiac Surgery, andW. Gerald and Patricia R. Austen Distinguished Scholar in Cardiac Surgery,Massachusetts General Hospital, Boston, MA, USA






CAMBRIDGE UNIVERSIT Y PRESSCambridge, New York, Melbourne, Madrid, Cape Town,Singapore, Sao Paulo, Delhi, Tokyo, Mexico City

Cambridge University PressThe Edinburg Building, Cambridge CB2 8RU, UK

Published in the United States of America by CambridgeUniversity Press, New York

www.cambridge.orgInformation on this title: www.cambridge.org/9780521197533

c© Cambridge University Press 2011

This publication is in copyright. Subject to statutory exceptionand to the provisions of relevant collective licensingagreements, no reproduction of any part maytake place without the written permission of CambridgeUniversity Press.

First published 2011

Printed in the United Kingdom at the University Press,Cambridge

A catalogue record for this publication is available from theBritish Library.

Library of Congress Cataloguing in Publication dataOrgan transplantation : a clinical guide / edited byAndrew Klein, Clive J. Lewis, Joren C. Madsen.

p. ; cm.Includes bibliographical references and index.ISBN 978-0-521-19753-3 (hardback)1. Transplantation of organs, tissues, etc.2. Transplantation immunology. I. Klein, Andrew.II. Lewis, Clive J., 1968– III. Madsen, Joren C., 1955–[DNLM: 1. Organ Transplantation. 2. TransplantationImmunology. WO 660]RD120.7.O717 2011617.9′5 – dc22 2011002165

ISBN 978-0-521-19753-3 Hardback

Cambridge University Press has no responsibility for thepersistence or accuracy of URLs for external or third-partyinternet websites referred to in this publication, and does notguarantee that any content on such websites is, or will remain,accurate or appropriate.

Every effort has been made in preparing this book to provideaccurate and up-to-date information which is in accord withaccepted standards and practice at the time of publication.Although case histories are drawn from actual cases, everyeffort has been made to disguise the identities of the individualsinvolved. Nevertheless, the authors, editors and publishers canmake no warranties that the information contained herein istotally free from error, not least because clinical standards areconstantly changing through research and regulation. Theauthors, editors and publishers therefore disclaim all liabilityfor direct or consequential damages resulting from the use ofmaterial contained in this book. Readers are strongly advised topay careful attention to information provided by themanufacturer of any drugs or equipment that they plan to use.






Contents

List of contributors viiForeword xiPreface xiiiList of abbreviations xv

Section 1 – General1 Historical perspectives 1

John Dunning and Sir Roy Calne

2 Immunological principles of acuterejection 9Fadi G. Issa, Ryoichi Goto, and Kathryn J. Wood

3 Immunosuppression: Past, present,and future 19Vineeta Kumar and Robert S. Gaston

4A Major complications – cancer 31Bimalangshu R. Dey and Thomas R. Spitzer

4B Major complications – pathology ofchronic rejection 38Yael B. Kushner and Robert B. Colvin

4C Major complications – infection 46Camille Nelson Kotton

5 Organ donor management andprocurement 53Edward Cantu III and David W. Zaas

Section 2 – Heart6 Recipient selection 63

R.V. Venkateswaran and Jayan Parameshwar

7 Donor heart selection 70Kiran K. Khush and Jonathan G. Zaroff

8 Ventricular assist devices 76David G. Healy and Steven S.L. Tsui

9 Surgical procedure 83R.V. Venkateswaran and David P. Jenkins

10 Management during surgery 88Kate Drummond and Andrew A. Klein

11 Postoperative care and earlycomplications 94Mandeep R. Mehra

12 Long-term management andoutcomes 102Hari K. Parthasarathy and Clive J. Lewis

13 Pediatric heart transplantation 112Jacob Simmonds and Michael Burch

Section 3 – Lung14 Recipient selection 122

J.S. Parmar

15 Living donor lobar lungtransplantation 128Hiroshi Date

16 Surgical procedure 133Faruk Ozalp, Tanveer Butt, and StephanV.B. Schueler

17 Management during surgery 138David Ip and Peter Slinger

18 Postoperative care and earlycomplications 145Vlad Vinarsky and Leo C. Ginns

19 Long-term management andoutcomes 155Paul Corris

20 Pediatric lung transplantation 164Stuart C. Sweet and Samuel Goldfarb

v






Contents

Section 4 – Liver21 Recipient selection 173

Alex Gimson

22 Living donor liver transplantation 182Koji Hashimoto, Cristiano Quintini, andCharles Miller

23 Surgical procedure 190Simon J.F. Harper and Neville V. Jamieson

24 Peri-operative care and earlycomplications 199John Klinck and Andrew J. Butler

25 Long-term management andoutcomes 212William Gelson and Graeme J.M. Alexander

26 Pediatric liver transplantation 220Hector Vilca-Melendez and GiorginaMieli-Vergani

Section 5 – Kidney27 Recipient selection 231

Ernest I. Mandel and Nina E. Tolkoff-Rubin

28 Sensitization of kidney transplantrecipients 238Nick Pritchard

29 Live donor kidney donation 248Arthur J. Matas and Hassan N. Ibrahim

30 Surgical procedure 253Paul Gibbs

31 Peri-operative care and earlycomplications 258Lorna Marson and John Forsythe

32 Long-term management andoutcomes 265Sharon Mulroy and John D. Firth

33 Pediatric kidney transplantation 278Khashayar Vakili and Heung Bae Kim

Section 6 – Other abdominal organs34 Pancreatic transplantation 286

Dixon B. Kaufman

35 Pancreatic islet transplantation 295Heidi Yeh and James F. Markmann

36 Intestinal transplantation 303Stephen J. Middleton, Simon M. Gabe,Neville V. Jamieson, and Andrew J. Butler

Section 7 – Other37 Composite tissue allotransplantation:

Face transplantation 313Maria Siemionow and Can Ozturk

38 Hematopoietic stem celltransplantation 320Charles Crawley and Thomas R. Spitzer

39 Corneal transplantation 330Yvonne H. Luo and D. Frank P. Larkin

Section 8 – The transplant service40 UK and European service – legal and

operational framework 335Chris J. Rudge and Axel O. Rahmel

41 US transplant service – legal andoperational framework 347Walter K. Graham, Richard S. Luskin, andFrancis L. Delmonico

42 Conclusions 355Clive J. Lewis

Index 357Color plate section falls between pages 181 and 182.

vi






Contributors

Graeme J.M. Alexander, MA, MD, FRCPConsultant Hepatologist, Addenbrooke’s HospitalCambridge, UK

Heung Bae Kim, MDAssistant Professor of Surgery, Harvard MedicalSchool, and Director, Pediatric Transplant Center,Children’s Hospital Boston, Boston, MA, USA

Michael BurchLead Transplant Consultant, Consultant Cardiologist,Great Ormond Street Hospital for Sick Children,London, UK

Andrew J. Butler, MDConsultant, Department of Transplantation Surgery,Addenbrooke’s Hospital, Cambridge, UK

Tanveer Butt, FRCSDepartment of Cardiopulmonary Transplantation,The Newcastle upon Tyne Hospitals NHS FoundationTrust (NUTH), Freeman Hospital, High Heaton,Newcastle upon Tyne, UK

Roy Calne, MDYeah Ghim Professor of Surgery at the NationalUniversity of Singapore, Singapore

Edward Cantu III, MDAssociate Surgical Director of Lung Transplantation,University of Pennsylvania, Philadelphia, PA, USA

Robert B. Colvin, MDDepartment of Pathology, Massachusetts GeneralHospital, and Harvard Medical School, Boston,MA, USA

Paul Corris, MB, FRCPProfessor, Department of Respiratory Medicine,Freeman Hospital, Newcastle upon Tyne, UK

Charles CrawleyConsultant, Department of Hematology,Addenbrooke’s Hospital, Cambridge, UK

Hiroshi Date, MDProfessor, Department of Thoracic Surgery, KyotoUniversity Graduate School of Medicine,Kyoto, Japan

Francis L. Delmonico, MDMedical Director, New England Organ Bank, andProfessor of Surgery, Harvard Medical School,Massachusetts General Hospital, Boston, MA, USA

Bimalangshu R. Dey, MD, PhDBone Marrow Transplant Program, Department ofMedicine, Massachusetts General Hospital, andHarvard Medical School, Boston, MA, USA

Kate Drummond, MDFellow, Anaesthesia and Intensive Care, PapworthHospital, Cambridge, UK

John Dunning, MDConsultant Cardiothoracic Surgeon, PapworthHospital, Cambridge, UK

John D. Firth, DM, FRCPConsultant Physician and Nephrologist, CambridgeUniversity Hospitals Foundation Trust,Cambridge, UK

John Forsythe, MDConsultant Transplant Surgeon, Royal Infirmary ofEdinburgh, Edinburgh, UK

Simon M. GabeLennard Jones Intestinal Failure Unit, St Mark’sHospital, Northwick Park, Harrow,London, UK

vii






Contributors

Robert S. Gaston, MD, MRCPEndowed Professor, Transplant Nephrology, andMedical Director, Kidney and PancreasTransplantation, Division of Nephrology,University of Alabama at Birmingham,Birmingham, AL, USA

William Gelson, MD, MRCPConsultant Surgeon, Department of TransplantSurgery, Addenbrooke’s Hospital, Cambridge, UK

Paul GibbsConsultant Surgeon, Department of TransplantSurgery, Addenbrooke’s Hospital, Cambridge, UK

Alex GimsonConsultant Physician, Department of Hepatology,Addenbrooke’s Hospital, Cambridge, UK

Leo C. Ginns, MDMedical Director, Lung Transplantation,Massachusetts General Hospital, and AssociateProfessor of Medicine, Harvard Medical School,Boston, MA, USA

Samuel Goldfarb, MDAttending Physician, Division of PulmonaryMedicine, Children’s Hospital of Philadelphia;Medical Director, Lung and Heart/Lung TransplantPrograms, and Assistant Professor of Pediatrics,University of Pennsylvania School of Medicine,Philadelphia, PA, USA

Ryoichi Goto, MDClinical Research Fellow, Nuffield Departmentof Surgery, University of Oxford, Oxford, UK

Walter K. Graham, JDExecutive Director, United Network forOrgan Sharing, Richmond, VA, USA

Simon J.F. HarperClinical Lecturer in Transplantation, Universityof Cambridge and Addenbrooke’s Hospital,Cambridge, UK

Koji Hashimoto, MD, PhDDepartment of Surgery, Cleveland Clinic, Cleveland,OH, USA

David G. Healy, PhD, FRCSI (C-Th)Honorary Fellow, Department of CardiothoracicSurgery, Papworth Hospital, Cambridge, UK

Hassan N. Ibrahim, MDDepartment of Medicine, University of Minnesota,Minneapolis, MN, USA

David Ip, MBBS, FANZCAAnaesthesia Fellow, Toronto General Hospital,Toronto, ON, Canada

Fadi G. Issa, MA, BMBCh, MRCSClinical Research Fellow, Nuffield Department ofSurgery, University of Oxford, Oxford, UK

Neville V. JamiesonConsultant Transplantation and HPB Surgeon,University of Cambridge and Addenbrooke’sHospital, Cambridge, UK

David P. Jenkins, MB BS, FRCS (Eng),MS (Lond), FRCS (CTh)Consultant Cardiothoracic Surgeon,Papworth Hospital, Cambridge, UK

Dixon B. Kaufman, MD, PhDProfessor and Chief, Division of Transplantation,Department of Surgery, University of Wisconsin,Madison, WI, USA

Kiran K. Khush, MD, MASDivision of Cardiovascular Medicine, Department ofMedicine, Stanford University, Stanford, CA, USA

Heung Bae Kim, MDDirector, Pediatric Transplant Center, Department ofSurgery, Children’s Hospital Boston, and AssociateProfessor of Surgery, Harvard Medical School,Boston, MA, USA

Andrew A. Klein, MDConsultant, Cardiothoracic Anaesthesia andIntensive Care, Papworth Hospital, Cambridge, UK

John Klinck, MDConsultant Anesthetist, Addenbrooke’s Hospital,Cambridge, UK

viii






Contributors

Camille Nelson Kotton, MDClinical Director, Transplant and Immuno-compromised Host Infectious Diseases,Infectious Diseases Division, Massachusetts GeneralHospital, Boston, MA, USA

Vineeta Kumar, MDAssistant Professor of Medicine and Director,Transplant Nephrology Fellowship Program, Divisionof Nephrology, University of Alabama atBirmingham, Birmingham, AL, USA

Yael B. Kushner, MDDepartment of Pathology, Massachusetts GeneralHospital, and Harvard Medical School, Boston,MA, USA

D. Frank. P. Larkin, MD, FRCPI, FRCOphth2Consultant Surgeon, Moorfields Eye Hospital,London, UK

Clive J. Lewis, MB, BChir, MRCP, PhDConsultant, Department of Cardiology, TransplantUnit, Papworth Hospital,Cambridge, UK

Yvonne H. Luo, MA, MRCOphthSpecialist Registrar, Moorfields Eye Hospital,London, UK

Richard S. LuskinPresident and CEO, New England Organ Bank,Waltham, MA, USA

Ernest I. Mandel, MDClinical Fellow in Medicine, Brigham and Women’sHospital/Massachusetts General Hospital, Boston,MA, USA

James F. Markmann, MD, PhDChief, Division of Transplantation, Department ofSurgery, and Clinical Director, Transplant Center,Massachusetts General Hospital, and Professor ofSurgery, Harvard Medical School, Boston, MA, USA

Lorna MarsonSenior Lecturer in Transplant Surgery, University ofEdinburgh, Edinburgh, UK

Arthur J. Matas, MDDepartment of Surgery, University of Minnesota,Minneapolis, MN, USA

Mandeep R. Mehra, MBBS, FACP, FACCDivision of Cardiology, Department of Medicine,University of Maryland School of Medicine,Baltimore, MD, USA

Stephen J. Middleton, MA, MD, FRCP, FAHEConsultant Physician, Department ofGastroenterology, Addenbrooke’s Hospital,Cambridge University, Cambridge, UK

Giorgina Mieli-Vergani, MD, PhD, FRCP, FRCPCHAlex Mowat Professor of Paediatric Hepatology,Institute of Liver Studies, King’s College LondonSchool of Medicine, London, UK

Charles MillerDirector of Liver Transplantation, Cleveland Clinic,Cleveland, OH, USA

Sharon Mulroy, MDLocum Consultant Nephrologist, Department ofRenal Medicine, Addenbrooke’s Hospital, Cambridge,UK

Faruk Ozalp, MRCSDepartment of Cardiopulmonary Transplantation,The Newcastle upon Tyne Hospitals NHS FoundationTrust, Freeman Hospital, High Heaton, Newcastleupon Tyne, UK

Can Ozturk, MDDermatology and Plastic Surgery Institute, ClevelandClinic, Cleveland, OH, USA

Jayan Parameshwar, MD, MPhil, FRCPConsultant Cardiologist, Advanced Heart Failure andTransplant Programme, Papworth Hospital,Cambridge, UK

J.S. Parmar, BM, PhD, FRCPConsultant Transplant Physician (Respiratory),Transplant Unit, Papworth Hospital, PapworthEverard, Cambridge, UK

Hari K. Parthasarathy, MD, MRCPTransplant Unit, Papworth Hospital,Cambridge, UK

Nick Pritchard, BSc, MBBS, PhD, FRCPConsultant Physician, Department of RenalMedicine, Addenbrooke’s Hospital, Cambridge, UK

ix






Contributors

Cristiano Quintini, MDDepartment of General Surgery, Cleveland Clinic,Cleveland, OH, USA

Axel O. RahmelMedical Director, Eurotransplant InternationalFoundation, Leiden, The Netherlands

Chris J. Rudge, FRCSNational Clinical Director for Transplantation,Department of Health, London, UK

Stephan V.B. Schueler, MD, PhD, FRCSConsultant Surgeon, Department ofCardiopulmonary Transplantation, The Newcastleupon Tyne Hospitals NHS Foundation Trust,Freeman Hospital, High Heaton, Newcastle uponTyne, UK

Maria Siemionow, MD, PHD, DSCProfessor of Surgery, Dermatology and PlasticSurgery Institute, Cleveland Clinic,Cleveland, OH, USA

Jacob SimmondsSpecialist Registrar, Department of CardiothoracicTransplantation, Great Ormond Street Hospital,London, UK

Peter Slinger, MD, FRCPCProfessor of Anesthesia, Toronto General Hospital,Toronto, ON, Canada

Thomas R. Spitzer, MDDirector, Bone Marrow Transplant Program,Massachusetts General Hospital, andProfessor of Medicine, Harvard Medical School,Boston, MA, USA

Stuart C. Sweet, MD, PhDMedical Director, Pediatric Lung TransplantProgram, and Associate Professor of Pediatrics,Department of Pediatrics, Washington University,St. Louis, MO, USA

Nina E. Tolkoff-Rubin, MDMedical Director for Renal Transplantation,Massachusetts General Hospital, and Professor

of Medicine, Harvard Medical School, Boston,MA, USA

Steven S.L. Tsui, MA (Cantab), MD, FRCS (Eng),FRCS (C-Th)Consultant Surgeon and Director of Transplantation,Papworth Hospital, Cambridge, UK

Khashayar Vakili, MDInstructor in Surgery, Harvard Medical School, andDepartment of Surgery, Children’s Hospital Boston,Boston, MA, USA

R.V. Venkateswaran, MS, MD, FRCS-CThFellow, Department of Cardiothoracic Surgery,Papworth Hospital, Papworth Everard,Cambridge, UK

Hector Vilca-Melendez, MD, PhDConsultant Surgeon, Institute of Liver Studies, King’sCollege Hospital, London, UK

Vladimir Vinarsky, MDClinical Fellow in Medicine, Massachusetts GeneralHospital, Boston, MA, USA

Kathryn J. Wood, DPhilProfessor of Immunology, Nuffield Department ofSurgery, University of Oxford, Oxford, UK

Heidi Yeh, MDAssistant in Surgery, Massachusetts GeneralHospital, and Instructor in Surgery, Harvard MedicalSchool, Boston, MA, USA

David W. ZaasMedical Director, Lung Transplantation, andVice-Chair for Clinical Practice, Departmentof Medicine, Duke University, Durham, NC,USA

Jonathan G. Zaroff, MDDivision of Cardiology, Kaiser Permanente,San Francisco, CA, USA

x






Foreword

The ever expanding nature of transplantation meansthat a book aimed at encompassing all aspects of alltransplant subspecialties would be vast. Instead, thisbook focuses on the clinical aspects of transplanta-tion. It provides a concise yet comprehensive guide tothe art and science of caring for transplant patients.It will undoubtedly provide an excellent resource forphysicians, surgeons, anesthesiologists and, indeed, alltransplant practitioners – medical and non-medical. Itwill also be of interest to patients and their familiesbecause it is written and presented in an easy-to-readformat.

This text provides state-of-the-art knowledge fromexperts in their respective fields. As such, it willbecome an essential companion for anyone involvedin transplantation, especially those at the beginning oftheir careers. It will be available as an e-book, and inthe traditional print form. I am sure that you will enjoy,Organ Transplantation – A Clinical Guide.

Thomas E. Starzl, MD, PhDProfessor of Surgery and Distinguished ServiceProfessor, University of Pittsburgh

xi






Preface

The field of solid organ transplantation has developedenormously in the last three decades and what was pio-neering surgery has now become routine. Outcomesare no longer considered in terms of 1-year survival,but clinicians and patients are looking to 20 yearsand beyond. The current success of transplantation isbased on many different factors: developments in sur-gical technique, better immunosuppression, improvedanesthetic and intensive care, improved microbiology,and close collaboration between – all those involved inthe transplant pathway have contributed.

However, there are still many problems to be over-come and success has brought its own challenges.The adverse impact of immunosuppression – suchas increased risk of some cancers and infections,increased cardiovascular and cerebrovascular disease,diabetes and renal failure – have not yet been avoidedby the development of more effective and specificagents; tolerance remains elusive, although inducingoperational tolerance is perhaps less distant now thanit was a decade ago. In many situations, recurrentdisease is yet to be overcome. Most transplant recip-ients still have a reduced life expectancy comparedwith the normal population and so clinicians are nowfocussing on maintaining the quality and length oflife.

Overcoming many of the technical barriers totransplantation has increased the number of peoplewho could benefit from transplantation and high-lighted the need for more donors. Donation rates varybetween countries and many factors contribute to thisvariation: cultural, logistical, financial, legal, and med-ical. The success of initiatives to reduce prematuredeath from road accidents and cardiovascular andcerebrovascular disease are of course hugely welcomebut have resulted in a reduction in the potential donor

pool, and those who are potential donors are becom-ing older and heavier so that the number and quality ofretrieved organs is falling. The reduction in the tradi-tional donor pool has encouraged clinicians to look atadditional sources of donors, including living donorsand donors after circulatory death. These approacheswill go some way toward mitigating the impact of theshrinking traditional donor pool; however, the widen-ing gap between need and supply does bring into focusthe moral, ethical, and legal implications of the intro-duction of policies for what is, effectively, the rationingof life-saving organs.

Transplantation remains a high-risk procedureand its risks have to be balanced against those ofongoing medical management. Donated organs arenot free of risks of transmission of cancer or infec-tion and should be considered “second hand” ratherthan new. Recipient’s expectations must be managedappropriately. An excessive focus on outcomes andavoidance of risk will encourage risk-averse behav-ior by clinicians and may inhibit some surgeonsfrom remaining in this challenging field. Therefore,unless regulation is maintained at an appropriate level,over-monitoring will ultimately adversely affect therecipient.

The future of transplantation is, for the moment,secure and there is little doubt that the need fortransplantation will continue to exceed the supply oforgans. Although many problems have been over-come, many challenges remain. We are encouragedby the progress in immune tolerance, regenerativemedicine, organ support, and even xenotransplanta-tion. However, there is much yet to be learned andthen applied to patients. The race between perfect-ing the process of organ transplantation-fabricationon one hand and the curing of diseases that lead

xiii






Preface

to organ failure and the need for transplantationon the other, is on. Fortunately, however, no matterwhich side wins, it the patient who is ultimately thevictor.

This book, with contributions from experts in thebroad field of transplantation from all over the world,provides an authoritative account of where transplan-tation has come from, where it is now, and where itmight go in the future. The state-of-the-art knowledgecontained within this volume will help make all whoread it better caregivers to recipients of organ trans-

plants and better prepared to embrace the excitingfuture of our field.

Andrew A. Klein, MDConsultant, Cardiothoracic Anaesthesia andIntensive Care, Papworth Hospital, Cambridge, UK

James Neuberger, DM, FRCPHonorary Professor of Medicine, University ofBirmingham, and Associate Medical Director,Organ Donation and Transplantation, NHS Bloodand Transplant, Bristol, UK

xiv






Abbreviations

6-MP 6-mercaptopurineA2ALL Adult-to-Adult Living Donor Liver

Transplantation Cohort StudyABOi ABO incompatibleABVC doxorubicin, bleomycin, vinblastine,

and dacarbazineACAID Anterior chamber–associated

immune deviationACD acquired cystic diseaseACE angiotensin-converting enzymeACOT Advisory Committee on

TransplantationACR acute cellular rejectionACT activated clotting timeADCC antibody-dependent cell-mediated

cytotoxicityADH anti-diuretic hormoneAHR acute humoral rejectionaHUS atypical HUSaICB atraumatic intracranial bleedAIDS acquired immune deficiency

syndromeAIH autoimmune hepatitisALF acute liver failureALG anti-lymphocyte globulinAMR antibody mediated rejectionAP-1 activator protein 1APC antigen-presenting cellAPOLT auxiliary partial orthotopic liver

transplantationARB angiotensin receptor blockerARDS acute respiratory distress syndromeATC anti-thymocyte globulinATG antithymocyte globulinATN acute tubular necrosisATP adenosine triphosphate productionAV atrioventricularAZA azathioprineBASM biliary atresia splenic malformationBCC basal cell carcinoma

BKV BK virusBLT bilateral lung transplantationBMD bone mineral densityBMI body mass indexBNP B-type natriuretic peptideBODE body mass index, airflow obstruction,

dyspnea, and exercise capacityBOS bronchiolitis obliterans syndromeBTT bridging to transplantC3 complement component 3C4d complement component 4dCAN chronic allograft nephropathyCAV cardiac allograft vasculopathyCAV coronary artery vasculopathyCBD common bile ductCBP cardiopulmonary bypassCD3 cluster of differentiation (CD) 3

moleculeCDC complement-dependent cytotoxicity

cross-matchCDR chronic ductopenic rejectionCF cystic fibrosisCHOP cyclophosphamide, doxorubicin,

vincristine, and prednisoneCHR chronic humoral rejectionCIT cold ischemic timeCKD chronic kidney diseaseCmax maximum concentrationCMV cytomegalovirusCNI calcineurin inhibitorCNS central nervous systemCO carbon monoxideCOPD chronic obstructive pulmonary

diseaseCPB cardiopulmonary bypassCPEX cardiopulmonary exercise testingCR complete remissionCRP C-reactive proteinCRT cardiac resynchronization

therapy

xv






List of abbreviations

c-SMAC central supramolecular activationcluster

CT computed tomographyCTA composite tissue allotransplantationCTL cytotoxic T cellCTLA-4 cytotoxic T-lymphocyte antigen 4CTTR Cincinnati Transplant Tumor

RegistryCVP central venous pressureCY cyclophosphamideCyA cyclosporineD donorD– no diarrheaD+ diarrhea associatedDAG diacylglycerolDBD donation after brain deathDC dendritic cellDCD donation after cardiac deathDEXA dual-energy X-ray absorptiometryDGF delayed graft functionDLCO diffusing capacity of carbon

monoxideDLI donor lymphocyte infusionDM1 type 1 diabetes mellitusDM2 type 2 diabetes mellitusDSA donor specific antibodiesDTC donor transplant coordinatorDTH delayed-type hypersensitivityDVT deep venous thrombosisEBV Epstein-Barr virusECD extended criteria donorECMO extracorporeal membrane

oxygenationEC-MPS enteric-coated mycophenolate

sodiumEF ejection fractioneGFR estimated glomerular filtration rateEHBA extra-hepatic biliary atresiaELITE Efficacy Limiting Toxicity EliminationENT ear, nose, and throatER endoplasmic reticulumESC embryonic stem cellESRD end-stage renal diseaseETT endotracheal tubeEVL everolimusEVLP ex vivo lung perfusionFasL Fas ligandFCXM flow cytometry cross-matchFDA US Food and Drug AdministrationFEF forced expiratory flow

FEF25–75% forced expiratory flow 25–75%FEV1 forced expiratory volume in 1 secondFLR future liver remnantFRC functional residual capacityFSGS focal segmental glomerulosclerosisFVC forced vital capacityGBM glomerular basement membraneG-CSF granulocyte colony-stimulating factorGDA gastroduodenal arteryGERD gastroesophageal reflux diseaseGFR glomerular filtration rateGI gastrointestinalGRWR graft-to-recipient body weight ratioGvHD graft-versus-host diseaseGvL Graft versus leukemiaHAR hyperacute rejectionHARI hepatic artery resistance indexHAT hepatic artery thrombosisHBV hepatitis B virusHCC hepatocellular carcinomaHCV hepatitis C virusHF heart failureHFSS Heart Failure Survival ScoreHHS Department of Health and Human

ServicesHHV human herpes virusHHV-8 human herpes virus type 8HIV human immunodeficiency virusHLA human leukocyte antigenHLAi HLA incompatibleHLT combined heart–lung transplantationHLT heart–lung transplantationHMGB-1 high-mobility group box 1 proteinHPC human progenitor cellHPV human papillomavirusHRQOL health related quality of lifeHRSA Health Resources and Services

AdministrationHSC hematopoietic stem cellsHSCT hematopoietic stem cell

transplantationHSP heat shock proteinHSV herpes simplex virusHT heart transplantHT heart transplantationHTA Human Tissue AuthorityHUS hemolytic uremic syndromeIBMIR immediate blood-mediated

inflammatory reactionICAM-1 intercellular adhesion molecule 1

xvi







ICD implantable cardioverter-defibrillatorICOS inducible T-cell costimulatorICP intra-cranial pressureICU intensive care unitIE islet equationIF/TA interstitial fibrosis and tubular

atrophyIFN interferonIFN� interferon �Ig immunoglobulinIgA immunoglobulin AIgG immunoglobulin GIHD ischemic heart diseaseIL interleukinIL-2 interleukin-2IL-2R interleukin-2 receptorIMP inosine monophosphateIMV inferior mesenteric veiniNO inhaled nitric oxideINR international normalized ratioINTERMACS International Registry for

Mechanically Assisted CirculatorySupport

IP3 inositol triphosphateIPAH idiopathic pulmonary arterial

hypertensionIPEX immune dysregulation,

polyendocrinopathy, enteropathyX-linked

IPF idiopathic pulmonary fibrosisIPTR International Pancreas Transplant

RegistryIRI ischemia/reperfusion injuryISHLT International Society for Heart and

Lung TransplantationiTreg inducible TregITU intensive treatment unitIV intravenousIVC inferior vena cavaIVIg intravenous immunoglobulinIVUS intravascular ultrasoundJak Janus kinaseJCV JC virusKS Kaposi’s sarcomaLAS lung allocation systemLCR late cellular rejectionLDH lactate dehydrogenaseLDLLT living donor lobar lung

transplantationLDLT living donor liver transplantation

LDLT living donor lung transplantationLFA-1 leukocyte function-associated

antigen 1LFA-1 lymphocyte-function associated

antigen-1LT liver transplantationLT lung transplantationLV left ventricleLV left ventricularLVAD left ventricular assist deviceLVEDP left ventricular end-diastolic

pressureLVH left ventricular hypertrophyMAC membrane attack complexMAG3 mercaptoacetyltriglycineMAP mitogen-activated proteinMAPK MAP kinaseMBD mineral bone diseaseMCSD mechanical circulatory support

devicesMELD Model for End-Stage Liver DiseaseMHC major histocompatability complexMHV middle hepatic veinmiH minor histocompatibilityMMF mycophenolate mofetilMMR measles, mumps, and rubellaMPA mycophenolic acidMPGN membranoproliferative

glomerulonephritisMPSC Membership and Professional

Standards CommitteeMRI magnetic resonance imagingMRR medical record reviewMRSA methicillin-resistant Staphylococcus

aureusmTOR mammalian target of rapamycinNAPRTCS North American Pediatric Renal

Trials and Collaborative StudiesNFAT nuclear factor of activated

T cellsNF-�B nuclear factor-�BNHL non-Hodgkin’s lymphomaNHS National Health ServiceNHSBT NHS Blood and TransplantNK natural killerNKT natural killer TNO nitric oxideNOD non-obese diabeticNODAT new-onset diabetes after

transplantation

xvii







NODAT new-onset diabetes aftertransplantation

NOTA National Organ Transplant ActNRM non-relapse mortalitynTreg naturally occurring TregNYHA New York Heart AssociationOB obliterative bronchiolitisOKT3 muromonab-CD3OLV one-lung ventilationOP osteoporosisOPO organ procurement organizationOPTN Organ Procurement and

Transplantation NetworkPA pulmonary arteryPAK pancreas after kidney transplantPAP pulmonary artery pressurePAS Periodic Acid-SchiffPCA patient-controlled analgesiaPCR polymerase chain reactionPCWP pulmonary capillary wedge pressurePDA UK Potential Donor AuditPDGF platelet-derived growth factorPEEP positive end expiratory pressurePGD primary graft dysfunctionPGE2 prostaglandin E2PGI2 prostacyclinPK pharmacokineticPKC protein kinase CPML progressive multifocal

leukoencephalopathyPMN polymorphonuclear neutrophilPN parenteral nutritionppm parts per millionPRA panel-reactive antibodyPRAISE Prospective Randomized Amlodipine

Survival EvaluationPRR pattern recognition receptorPSC primary sclerosing cholangitisp-SMAC peripheral SMACPT prothrombin timePTA pancreas transplant alonePTLD post-transplant lymphoproliferative

diseasePTM post-transplant malignancyPUVA psoralen and UVA therapyPVR pulmonary vascular resistancePVT portal vein thrombosisQoL quality of lifeR recipientRAD everolimus

RAS renal artery stenosisrATG rabbit ATGRBCs red blood cellsRCC renal cell carcinomaRCT randomized controlled trialRER respiratory exchange ratioRIC reduced intensity conditioningROS reactive oxygen speciesRR relative riskRSV respiratory syncytial virusRV right ventricleRV right ventricularRVAD right ventricular assist deviceRVI respiratory viral infectionsSA sinoatrialSARS severe acute respiratory syndromeSCC squamous cell carcinomaSCID severe combined immunodeficiencySFSS small-for-size syndromeSIOPEL International Childhood Liver

Tumour Strategy Group of theInternational Society of PaediatricOncology

SIRS systemic inflammatory responsesyndrome

SLT single lung transplantationSMA smooth muscle antibodySMA superior mesenteric arterySMV superior mesenteric veinSOT solid organ transplantSPK simultaneous pancreas and kidney

transplantSRL sirolimusSRTR Scientific Registry of Transplant

RecipientsSRTR US Scientific Registry of Transplant

RecipientsSVC superior vena cavaSVR systemic vascular resistanceT3 triiodothyronineT4 tetraiodothyronineTA transplant arteriopathyTAC tacrolimusTAH total artificial heartTBBx transbronchial biopsyTBI total body irradiationTCD T-cell depletedTCMR T-cell mediated rejectionTCR T-cell receptorTEA thoracic epidural anesthesia

xviii







TEE transesophageal echocardiographyTEG thromboelastographyTG transplant glomerulopathyTGF� transforming growth factor �Th helper T cellTIVA total intravenous anesthesiaTLC total lung capacityTLCO transfer coefficient for carbon

monoxideTLI total lymphoid irradiationTLR Toll-like receptorTMA thrombotic microangiopathyTn troponinTNF tumor necrosis factorTNF-� tumor necrosis factor alphaTNFR TNF receptorTPEX therapeutic plasma exchangeTPG transpulmonary gradientTPG transpulmonary pressure gradient

TR tricuspid regurgitationTreg regulatory T cellTSH thyroid-stimulating hormoneUCLA University of California, Los AngelesUKELD United Kingdom Model for

End-Stage Liver DiseaseUNOS United Network for Organ SharingUTI urinary tract infectionVA arteriovenousVAD ventricular assist deviceVBDS vanishing bile duct syndromeVOD veno-occlusive diseaseVRE vancomycin-resistant Enterococcus

faecalisVTE venous thromboembolismVV venovenousVZV varicella zoster virusWHO World Health OrganizationWU Wood units

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