Abdominal Organ Transplantation

Abdominal OrganTransplantationState of the Art

EDITED BY

Nizam MamodeConsultant Transplant SurgeonReader in Transplant SurgeryGuy’s and St Thomas’ HospitalGreat Ormond Street HospitalLondon, UK

Raja KandaswamyProfessor and Vice-ChiefDivision of TransplantationDepartment of SurgeryUniversity of MinnesotaMinneapolis, MN, USA

A John Wiley & Sons, Ltd., Publication

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Abdominal organ transplantation : state of the art / edited by Nizam Mamode,Raja Kandaswamy.

p. ; cm.Includes bibliographical references and index.ISBN 978-1-4443-3432-6 (cloth)I. Mamode, Nizam. II. Kandaswamy, Raja.[DNLM: 1. Abdomen–surgery. 2. Organ Transplantation–methods. WI 900]

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1 2013

Contents

List of Contributors, vii

Foreword, xi

Chapter 1 Living Donation: The Gold Standard, 1Leonardo V. Riella and Anil Chandraker

Chapter 2 New Surgical Techniques in Transplantation, 17Adam D. Barlow and Michael L. Nicholson

Chapter 3 Living-donor Liver Transplantation, 33Abhideep Chaudhary and Abhinav Humar

Chapter 4 Antibody-incompatible Transplantation, 56Nizam Mamode

Chapter 5 Pancreas Transplantation, 80Rajinder Singh, David E.R. Sutherland, and Raja Kandaswamy

Chapter 6 Allotransplantation of Pancreatic Islets, 107Maciej T. Juszczak and Paul R.V. Johnson

Chapter 7 Novel Cell Therapies in Transplantation, 138Paul G. Shiels, Karen S. Stevenson, Marc Gingell Littlejohn, and Marc Clancy

Chapter 8 Intestinal Transplantation, 150Khalid M. Khan, Tun Jie, Chirag S. Desai, and Rainer W.G. Gruessner

Chapter 9 Pediatric Renal Transplantation, 163Stephen D. Marks

Chapter 10 Immunosuppressive Pharmacotherapy, 177Steven Gabardi and Anil Chandraker

Chapter 11 Conclusion, 209Nizam Mamode and Raja Kandaswamy

Index, 213

v

List of Contributors

Adam D. BarlowSpecialist Registrar in General & Transplant SurgeryDepartment of Transplant SurgeryUniversity Hospitals of LeicesterLeicesterUK

Anil Chandraker, MD, FASN, FRCPAssociate Professor of MedicineMedical Director of TransplantationRenal DivisionBrigham and Women’s HospitalHarvard Medical SchoolBoston, MAUSA

Abhideep Chaudhary, MD, MBBS, MSClinical Fellow in Transplantation SurgeryUniversity of Pittsburgh, Medical Center (UPMC)Pittsburgh, PAUSA

Marc ClancyHonorary Clinical Senior LecturerSchool of MedicineUniversity of GlasgowGlasgowUK

Chirag S. Desai, MDDepartment of SurgeryUniversity of Arizona College of MedicineTucson, AZUSA

vii

viii List of Contributors

Steven Gabardi, PharmD, BCPSRenal Division/Departments of Transplant Surgery and Pharmacy ServicesBrigham and Women’s Hospital and Department of MedicineHarvard Medical SchoolBoston, MAUSA

Marc Gingell LittlejohnInstitute of Cancer SciencesCollege of Medical, Veterinary and Life SciencesUniversity of GlasgowGlasgowUK

Rainer W.G. Gruessner, MD, FACSProfessor of Surgery and Immunology ChairmanDepartment of SurgeryUniversity of Arizona College of MedicineTucson, AZUSA

Abhinav Humar, MDProfessor of SurgeryUniversity of Pittsburgh, Medical Center (UPMC)Pittsburgh, PAUSA

Tun Jie, MD, MS, FACSAssistant Professor of SurgeryGeneral Surgery/Abdominal Transplant/Hepatopancreatic and biliary

SurgeryDepartment of SurgeryUniversity of Arizona College of MedicineTucson, AZUSA

Paul R.V. Johnson, MBChB, MA, MD, FRCS(Eng +Edin),FRCS(Paed.Surg), FAAP

Professor of Paediatric Surgery University of OxfordDirector of DRWF Human Islet Isolation Facility and Oxford Islet

Transplant ProgrammeConsultant Paediatric SurgeonJohn Radcliffe HospitalFellow at St Edmund HallUniversity of OxfordOxfordUK

List of Contributors ix

Maciej T. JuszczakIslet Transplant Programme, Oxford Centre for Diabetes, Endocrinology

and Metabolism, and Islet Transplant Research GroupNuffield Department of Surgical SciencesUniversity of OxfordOxfordUK

Raja Kandaswamy, MD, FACSProfessor and Vice-Chief, Division of TransplantationDepartment of SurgeryUniversity of MinnesotaMinneapolis, MNUSA

Khalid M. Khan, MBChB, MRCPAssociate Professor DirectorPediatric Liver & Intestine Transplant ProgramUniversity of ArizonaTucson, AZUSA

Nizam Mamode, BSc, MB ChB, MD, FRCS, FRCS(Gen)Consultant Transplant SurgeonReader in Transplant SurgeryGuy’s and St Thomas’ HospitalGreat Ormond Street HospitalLondonUK

Stephen D. Marks, MD, MSc, MRCP, DCH, FRCPCHConsultant Paediatric NephrologistDepartment of Paediatric NephrologyGreat Ormond Street Hospital for Children NHS TrustLondonUK

Michael L. Nicholson, MD, DSc, FRCSProfessor of Transplant SurgeryDepartment of Transplant SurgeryUniversity Hospitals of LeicesterLeicesterUK

x List of Contributors

Leonardo V. Riella, MD, PhDInstructor in MedicineTransplant Research CenterRenal DivisionBrigham and Women’s HospitalHarvard Medical SchoolBoston, MAUSA

Paul G. ShielsDepartment of SurgeryUniversity of GlasgowWestern Infirmary GlasgowGlasgowUK

Rajinder SinghConsultant Transplant SurgeonGuy’s and St Thomas’ HospitalGreat Ormond Street HospitalLondonUK

Karen S. StevensonInstitute of Cancer SciencesCollege of Medical, Veterinary and Life SciencesUniversity of GlasgowGlasgowUK

David E.R. Sutherland, MD, PhDProfessorDepartment of SurgeryUniversity of MinnesotaMinneapolis, MNUSA

Foreword

This miscellaneous collection of articles on new developments in organtransplantation will be of very considerable interest to organ transplantclinicians. The chapters range from living donation of the kidney andliver to intestinal and pancreas the kidney, with a very good chapteron new surgical techniques in transplantation. In addition there is acomprehensive chapter on ABO incompatible renal transplantation andtransplantation in the patient that is highly sensitized to HLA. There is ashort review of the current status of pancreatic islet transplantation as wellas an extensive review of new developments in pancreas transplantation.Furthermore paediatric renal transplantation is well covered and thereare interesting contributions on novel cell therapies in transplantation aswell as on immunosuppressive therapies, concentrating on more recentdevelopments in this area. The final chapter by the two editors reviewsthe status of renal, liver, pancreas and intestinal transplantation, but inparticular outlines the problems that still have to be resolved. The editorsrecognise that the current one year graft survival rates are at a level that wasnot considered remotely possible even as little as 20 years ago but accept thatthe longer term outcomes are still disappointing despite the introductionof many new immunosuppressive strategies. But in general they are veryoptimistic about the future.

Overall this book will be considered a very good read by the transplantclinician.

Sir Peter J Morris AC, FRSDirector, Centre for Evidence in Transplantation,Royal College of Surgeons of England and London School of Hygiene andTropical Medicine.Emeritus Nuffield Professor of Surgery, University of Oxford.Past President, Royal college of Surgeons.Honorary Professor, University of London.

xi

1 Living Donation: The GoldStandardLeonardo V. Riella and Anil ChandrakerRenal Division, Brigham and Women’s Hospital, Harvard Medical School, USA

Introduction

The first successful transplant occurred in Boston in 1954, when a surgicalteam under the direction of Joseph Murray removed a kidney from ahealthy donor and transplanted it into his identical twin, who had chronicglomerulonephritis [1]. The organ functioned immediately and the recipientsurvived for 9 years, after which time his allograft failed from what wasthought to be recurrent glomerulonephritis. More than 50 years have passedsince that breakthrough achievement, and transplantation has progressedfrom an experimental modality to standard of care. The introductionof immunosuppressive drugs such as azathioprine, prednisone, and latercalcineurin inhibitors has led to better outcomes and, along with technicalbreakthroughs, expanded the pool of organs available to deceased andhuman leukocyte antigen (HLA)-mismatched donors.

Kidney transplantation has become the preferred therapeutic option forpatients with end-stage kidney disease (ESKD), leading to better patientsurvival and quality of life. It is also more cost-effective than dialysis[2–4]. Unfortunately, the incidence of ESKD has risen steadily in the pastseveral decades, creating a shortage of available organs for patients on thekidney-transplant waiting list (Table 1.1).

This growth in ESKD is related to the increased incidence of diabetes,obesity, and hypertension, combined with the improvement in treatmentfor concurrent health problems such as ischemic heart disease and stroke.The supply of organs from deceased donors has not followed the sameupward trend, resulting in an ever-widening gap between eligible potentialtransplant recipients and available organs (Table 1.2).

In 2009, only 18% of patients on the waiting list for kidney transplantationreceived an organ [5]. The average waiting time for kidneys from deceaseddonors in the USA is more than 3 years, and in some geographic areas itis more than 5 years (Table 1.3)—waiting times that are sometimes longerthan the average life expectancy of middle-aged and older persons withESKD [6]. In line with these numbers, a recent study indicates that even

Abdominal Organ Transplantation: State of the Art, First Edition.Edited by Nizam Mamode and Raja Kandaswamy.© 2013 Blackwell Publishing Ltd. Published 2013 by Blackwell Publishing Ltd.

1

2 Abdominal Organ Transplantation

Table 1.1 Waiting list for different organs inthe USA. OPTN, Organ Procurement andTransplantation Network. Data from [5].

Waiting list candidatesOPTN 2010

Number

All 107,075Kidney 84,495Pancreas 1,458Kidney/Pancreas 2,182Liver 15,948Intestine 248Heart 3,173Lung 1,844Heart/Lung 75

Table 1.2 Growth of the kidney-transplant waiting listcompared to donor type in the USA. Data from [5].

2009 1999 1989

Waiting List 84,495 40,825 17,786All type donors 14,631 10,862 5,929Deceased Donors 8,021 5,824 4,011Living Donors 6,610 5,038 1,918% Living donors 45% 46% 32%

Table 1.3 Time to transplant by organ type in the USA.Data from [5].

Organ type Time to transplant in 2004(median in days)

Kidney 1,219Pancreas Transplant Alone 376Pancreas after Kidney 562Kidney-Pancreas 149Liver 400Intestine 212Heart 166Lung 792

Living Donation: The Gold Standard 3

major alterations in the organ procurement process cannot reasonably beexpected to meet the demand for transplantable kidneys from decreaseddonors [7]. The imbalance between patient demand and the supply of organsfrom deceased donors has refocused attention on living kidney donors.

Epidemiology

Living-donor kidney transplantation is rapidly increasing in popularityworldwide and has surpassed the number of deceased donors in manytransplant centers [5]. In 2009, approximately 40% of all kidney donationswere from living donors, and most major transplant centers in the USA havebeen increasing the proportion of living donors, reaching more than 60% oftotal transplants in some. However, wide variations exist worldwide in theuse of living and deceased kidney donors. These differences reflect varyingmedical, ethical, social, and cultural values, as well as the availability ofdeceased-donor organs. For example, Spain has possibly the most efficientsystem of deceased-organ collection, with less than 5% of transplants beingfrom living donors. At the other end of the spectrum, strong cultural barriersin Japan have led to a preponderance of living-organ transplantation.Similarly, Turkey and Greece rely mainly on living donation as a source oforgan transplantation [8].

Several factors have influenced the expansion of living donation. Theadvent of laparoscopic nephrectomy has reduced the associated morbidityof kidney removal, making more donors receptive to an interruption of thehealthy course of their lives. Just as importantly, epidemiological data haveshown that irrespective of the HLA match or the donor–recipient relation-ship, recipients of living-donor kidneys (LDKs) fare better than those whoreceive deceased-donor kidneys (DDKs) (Figure 1.1). Finally, the devel-opment of stronger immunosuppression and desensitization techniqueshas overcome many of the biological barriers to successful transplantation,

100

80

60

40

20

Five-year survival Ten-year survival

Outcome:Graft failure or deathReturn to dialysis/retransplantDeath with function

Per

cent

sur

viva

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e of

end

poin

t

91 93 95 97 91 93 95

Year of transplant

9799 01

100

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Five-year survival Ten-year survival

Outcome:Graft failure or deathReturn to dialysis/retransplantDeath with function

Per

cent

sur

viva

l fre

e of

end

poin

t

91 93 95 97 91 93 95

Year of transplant

9799 01

Deceased donor transplants Living donor transplants

Figure 1.1 Outcomes of kidney transplants according to donor type. Graft-survival estimates are adjusted forage, gender, race, and primary diagnosis, using Cox proportional-hazards models. Conditional half-life estimatesdepend on first-year graft survival. (Reproduced from [6] The data reported here have been supplied by the UnitedStates Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of theauthor(s) and in no way should be seen as an official policy or interpretation of the U.S. government)

4 Abdominal Organ Transplantation

such as ABO incompatibility or the presence of low to medium titers ofantidonor HLA antibodies (Abs). Today, any person who is well and willingto donate may potentially be a live-kidney donor.

Advantages of living-kidney donation

It is well recognized that renal dysfunction is associated with acceler-ated heart disease. It has been estimated that mortality associated withcardiovascular disease is increased approximately 10-fold among patientswith ESKD, even after accounting for age, sex, race, and the presence ofdiabetes [9]. Successful kidney transplantation progressively reduces theincidence of cardiac mortality and is therefore associated with an over-all survival benefit in subjects undergoing kidney transplantation [10].Even in older transplant recipients and patients with ESKD secondary todiabetes or obesity—subgroups with higher perioperative cardiovascularcomplications—survival benefits persist [4,11].

One-year survival for a functioning transplant is 90% for recipients ofdeceased-donor transplants and 96% for recipients of transplants fromliving donors. After surviving the first year with a functioning transplant,50% of recipients of deceased- and living-donor transplants are projectedto be alive with a functioning transplant at 13 and 23 years, respectively.

The waiting time on dialysis has emerged as one of the strongestindependent modifiable risk factors for poor renal-transplant outcome [12],as can be seen in Figure 1.2. The presumed negative effect of prolongeddialysis is likely related to the impact of ESKD on cardiovascular morbidityand is observed in both living- and deceased-kidney recipients. However,even after a prolonged wait, patients who eventually receive a kidneytransplant still have a lower mortality than those who continued on dialysis[13]. The possibility of undergoing preemptive transplantation withoutthe need for dialysis gives the ESKD patients the best possible outcome[13–15]. With these observations in mind, until an optimal and timelysource of organs is developed to decrease the prolonged waiting times,living-kidney-donor transplantation provides the best alternative for mostpatients [13–15].

Living-kidney donation is an act of profound human generosity andcan be a source of much gratification for all parties involved. Many donorsdescribe it as the most meaningful experience of their lives and the quality oflife of donors after transplantation is reported to be better than or equivalentto that of controls [16]. Nonetheless, given the highly asymmetric natureof the physical benefits arising from kidney donation, a careful psychiatricevaluation of the donor is essential, to assess the coercion-free, informed,and autonomous decision to proceed with the process.

The number of sensitized recipients has increased dramatically in thepast couple of years and these recipients usually face the greatest waitingtimes, due to the presence of preformed antibodies, and consequently havethe greatest mortality. Desensitization protocols have enabled them to planand receive an LDK at a determined time, but these protocols are expensive

Living Donation: The Gold Standard 5

100

37

71

76

84

94

71

62

58

48

29

80

60

40

20

0

Cadaveric

Living

Pre-emptive

<6 months

12 months

Dialys

is tim

e

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>24 months

Gra

ft lo

ss p

er 1

000

patie

nts

0

20

40

60

80

100

Figure 1.2 Comparison of rates of graft loss associated with living- and deceased (cadaveric)-donor transplan-tation according to time on dialysis prior to transplantation [12]. (Reproduced from [12], Copyright © 2002, (C)2002 Lippincott Williams)

and labor-intensive, and in the USA have been implemented only forsmall numbers of patients. While successful in the short-term, the long-term outcomes remain unknown; these techniques are discussed further inChapter 5. Another potential option for such patients is a paired-kidneyexchange (PKE), which is discussed in more detail later in this chapter. Formany years, immunological barriers were thought to be the largest hurdlein transplantation; today, many cite the acute shortage of organs as themajor limitation.

Finally, the administration of donor-derived cells into the recipientin order to induce immunological hyporesponsiveness to the solid-organtransplant and minimize the need for immunosuppression has recentlybeen explored. This hyporesponsiveness was thought to occur due to thegeneration of mixed chimerism, immune deviation, and/or generation of aregulatory immunological phenotype. Kawai et al. have recently publisheda report on a small number of successful cases of combined bone-marrowand kidney transplant in HLA single-haplotype mismatched, living, relateddonors, with the use of a nonmyeloablative preparative regimen. Fourout of five recipients were able to discontinue all immunosuppressivetherapy 14 months after transplantation, opening new possibilities forthe induction of transplant tolerance with living-kidney donation, withconsequent improvement in long-term outcomes [17].

In summary, living donation provides one answer to the shortage of donororgans, allows preemptive transplantation, and leads to better long-term

6 Abdominal Organ Transplantation

graft survival. It also permits the introduction of new, tolerogenic strategies,and for many donors will be a very positive and meaningful experience.

Types of donor

Related versus unrelated donorsWhereas rates of kidney transplantation from living related donors increasedduring the 1990s, transplantation from living unrelated (including spousal)donors has increased rapidly over the past decade, now accounting fornearly one-quarter of all transplantations from living donors in the USA(Figure 1.3). In 1995, a landmark report by Terasaki and colleagues doc-umented that HLA-mismatched spousal transplants resulted in a graftsurvival superior to that of anything but identically matched kidneys fromdeceased donors [14]. This observation has influenced decisions regardingthe suitability of live donors who are spouses, friends of the recipient, oranonymous; there is little concern today about the degree of HLA matchingfor the crossmatch-negative recipient of a kidney from a living donor. Withdirected donation to loved ones or friends, concerns have arisen aboutthe intense pressure that can be put on people to donate, leading thosewho are reluctant to do so to feel coerced. Donor evaluation by a team ofphysicians other than that treating the recipient and a focus on the donor’sinterests when evaluating for donation minimize these risks. Furthermore,the general approach of simply reporting an unwilling donor as ‘unsuitable’is a safe method of protecting the donor’s decision without harming theirrelationship with the recipient.

Related4

3

Num

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of tr

ansp

lant

s (in

1,0

00s)

2

1

091 95 99 03 07

Distantly related

Spouse/partner

Unrelated directed

Paired donation

Other

Figure 1.3 Number of transplants from living donors, by donor relation. (Reproduced from[6] The data reported here have been supplied by the United States Renal Data System(USRDS). The interpretation and reporting of these data are the responsibility of the author(s)and in no way should be seen as an official policy or interpretation of the U.S. government)

Living Donation: The Gold Standard 7

Two Pair Exchange Three Pair Exchange

D1

D2

R1

R2

D1 D2

R1 R2 R3

D3

Figure 1.4 Examples of paired-kidney exchange (PKE). The traditional two-pair exchangeis shown on the left, while a more complex three-pair exchange is shown on the right. Thelatter occurs when one of the donors is incompatible with the reciprocal matched recipient.The three pairs can be arranged so that donor kidneys are simultaneously exchanged frompairs 1 to 2, 2 to 3, and 3 to 1. D, donor; R, recipient

Paired-kidney exchangeWhen available donors are incompatible with their intended recipients dueto ABO or HLA antibodies, many transplant centers participate in kidneylive-donor paired-exchange programs [18–20]. In a conventional PKEdonation (two-way exchange), two donor–recipient pairs surmount eachother’s incompatibility problem by simply exchanging donors (Figure 1.4).To ensure that both recipients receive their grafts, the two transplantationsare arranged simultaneously. The probability of finding a suitable donor–recipient pair for an exchange is greatly influenced by the pool size. Even ina successful large national PKE program, only around 50% of incompatiblepairs usually find a match and undergo a transplant—primarily due tothe blood-group imbalance in the pool of incompatible pairs [21]. Thereis a predominance of group A donors and group O recipients. Nationalmatching programs would make the likelihood of finding pairs greater andwould likely expand this type of organ transplantation.

PKEs have been performed in the USA for nearly a decade, as either single-center or, increasingly, multiregional programs. A recent report showed thatonly 334 paired donations had been carried out in the USA since 2000 [22].Legal and logistical barriers have been regarded as some of the major reasonsfor this poor success. Mutiregional data-sharing has substantially impactedPKE transplants [23]. There are now a number of regional PKE programswithin the United Network for Organ Sharing (UNOS), such as the NewEngland Program for Kidney Exchange (NEPKE), with 14 transplant centersin region 2, and the Alliance for Paired Donation, a 22-state coalition of 65transplant programs. We believe a centralized national PKE program wouldgive the greatest potential for matching incompatible donors. Such nationalschemes are currently operating in the Netherlands and the UK. The Dutchhave reported numerous challenges and barriers in their exchange program,and a flexible organization was key to creating alternative solutions [20].The rate of kidney transplantation can be increased by an average of 7–15%with a PKE program [24]. A recent study by the Dutch program suggestedthat the optimal chain length for living-kidney donation is three [25].In the UK experience, the use of altruistic, nondirected donors to start a

8 Abdominal Organ Transplantation

chain of transplants may offer the greatest potential to increase the numberof successful paired-kidney-donation transplants [26].

Altruistic donorsThe success of living unrelated kidney transplantation has influencedtransplant physicians to sanction the requests of individuals who wish tobe anonymous donors; that is, ‘‘nondirected or altruistic donors’’ [27].The motives of the nondirected donor should be established with care inorder to avoid a prospective donor’s intention of remedying a psychologicaldisorder via donation. In general, these kidneys are allocated according tothe waiting list for deceased-kidney donors [27]. Some centers advocatethe allocation of such organs into a PKE program, since this can resultin a domino effect and facilitate multiple transplants [23,28]. Directeddonation to a stranger—whereby donors choose to give to a specificperson with whom they have no prior emotional connection—is generallynot supported, primarily because of fears of commercial incentive orpsychological coercion [29].

Organ commercialism, which targets vulnerable populations (such asilliterate and impoverished persons, undocumented immigrants, prisoners,and political or economic refugees) in resource-poor countries, has beencondemned by international bodies such as the World Health Organization(WHO) for decades. In recent years, as a consequence of the increasing easeof Internet communication and the willingness of patients in rich countriesto travel to purchase organs, organ trafficking and transplant tourismhave grown into global problems. For example, as of 2006, foreignersreceived two-thirds of the 2000 kidney transplants performed annually inPakistan [30].

An international transplantation summit was held in Istanbul in 2008,which resulted in the ‘‘Declaration of Istanbul on Organ Trafficking andTransplant Tourism’’ [30–33]. This proclaims that the poor who selltheir organs are being exploited, whether by richer people within theirown country or by transplant tourists from abroad. Moreover, transplanttourists risk physical harm by unregulated and illegal transplantation. Par-ticipants in the Istanbul summit concluded that transplant commercialism,transplant tourism, and organ trafficking should be prohibited. They alsourged their fellow transplant professionals, individually and through theirorganizations, to put an end to these unethical activities and foster safe,accountable practices that meet the needs of transplant recipients whileprotecting donors.

Evaluation process for the live donor

Living donation appears contrary to the most fundamental concept of themedical profession: ‘‘primum non nocere’’ (‘‘first, do no harm’’). It exposesa healthy individual to the combined risks of major surgery and life with asingle kidney entirely for the benefit of another person. With that in mind,

Living Donation: The Gold Standard 9

LDK transplantation should only be undertaken if five essential conditionsare met:

● The risk to the donor is low.● The donor is fully informed of the risks and benefits as a donor● The donor is medically and psychosocially suitable.● The decision to donate is voluntary and entirely without coercion.● The transplant has a good chance of providing a successful outcome for

the recipient.

The Amsterdam consensus statement emphasizes that the purpose of theevaluation process is to ensure the overall health and well-being of the donor,minimizing unnecessary medical risk to both donor and recipient [34].It should quantify any potential technical difficulties that might compromisethe success of the nephrectomy and subsequent transplantation.

By general consensus, the optimal donor is an adult member of theimmediate family of a patient with ESKD [29]. However, the use ofemotionally related but genetically unrelated living donors has becomeincreasingly common worldwide, and this practice is supported by differentguidelines.

It is generally accepted that children (under the age of 18) should notdonate. As can be seen in Table 1.4, the majority of donors in the USAare between 35 and 49 years old; nonetheless, the upper age limit has beenadvancing in recent years. There are no set guidelines for an upper age limitfor donation, but most centers accept donors up to 70 years of age, after athorough investigation for underlying kidney disease, latent cardiovasculardisease, or malignancy.

A written informed consent is mandatory in most countries, with theunderstanding that consent can be withdrawn at any time. Moreover, thedonor evaluation should ideally be undertaken by a physician who is notdirectly involved with the proposed transplantation or the recipient’s care,in order to avoid any bias in the process. If the potential donor decidesnot to donate, the recipient is usually told that the donor is ‘unsuitable’;detailed information should not be given, nor should untrue statements be

Table 1.4 Number of kidney donors by age in the USA. Data from [5].

2009 2008 2007 2006 2005

All Ages 6,388 5,968 6,043 6,435 6,5716–10 Years 0 0 0 0 011–17 Years 3 0 0 1 018–34 Years 1,937 1,849 1,872 2,034 2,07835–49 Years 2,746 2,593 2,675 2,938 3,10350–64 Years 1,595 1,437 1,415 1,390 1,33265 + 107 89 81 71 58

10 Abdominal Organ Transplantation

made. Some controversial positions might arise when recipients are HIVpositive and the potential live-related donor is not aware of the recipient’sHIV status. The UK guidelines specify that the donor has the right to knowthe HIV status of the recipient in order to have a fully informed consent[35]. Others might argue that it is essential to inform the donor about thehigh-risk status of the recipient, but it is not necessary to give additionalmedical details about the recipient’s condition.

The financial aspects of donation should be discussed, due to theimportant implications early after transplant. The future donor must beaware of any expenses involved with the surgery and postsurgical care,as well as the loss of income in the first few weeks after transplant,where activity is limited. The latter is minimized significantly by the useof a laparoscopic approach to harvesting the donor kidney. Moreover,congressional legislation in the USA has provided an important model toremove financial disincentives to being a live donor: federal employees arenow afforded paid leave and coverage for travel expenses.

During the initial evaluation, the potential donor is assessed for anyobvious medical or psychosocial contraindication to donation in order toavoid unnecessary further investigation. Some laboratory information isalso collected during this first visit, including serum creatinine, blood count,urine dipstick, and ABO/HLA typing. The major contraindications for kid-ney donation are known diabetes, significant hypertension or proteinuria,a glomerular filtration rate (GFR) below the stated acceptable value for age,active infection, active malignancy, and recurrent kidney stones [36]. Serol-ogy for infectious diseases, chest x-ray (CXR), electrocardiogram (ECG),purified protein derivative (PPD) skin test for tuberculosis, and cancerscreening exams appropriate for age are also performed. As a final step, renalimaging is done, typically with a computed tomography (CT) angiogram,in order to assess kidney size, the renal vessels, and the urinary tract. Moredetails of the donor evaluation process can be found in [34] and [36].

Obesity in not considered a contraindication in either US or Europeanguidelines, but it has been documented that a body mass index (BMI) over30 significantly increases the perioperative complication rate, and someconcerns exist about the long-term consequences of nephrectomy.

The evaluation for hypertension should include blood pressure (BP)measurements by an experienced provider on three separate occasions;verification of elevated levels should be undertaken with ambulatory BPmonitoring as approximately 10–20% may be found to have normalBP [37,38]. If elevated BP is detected and the prospective donor is stillunder consideration, a CXR, ECG, echocardiogram, and ophthalmologicevaluation should be performed to look for secondary consequences ofhypertension. In addition, a 24-hour urine collection for albumin excretionor a spot urine for albumin–creatinine ratio should be performed, alongwith a urinalysis and a formal GFR measurement. If donors with hyperten-sion donate, they should be followed longitudinally by the transplant centerto ensure optimal treatment and monitoring of complications. Overall,hypertensive donors are increasingly being used in transplant centers dueto the limited availability of organs; however, more detailed information