Ethical issues in living donor kidney transplantation

The ethical issues of living donor kidney transplantation, which is the treatment of choice for patients with end-stage renal failure, are the focus of intense debate. Some of those issues are related to the safety of the operation for the donor, and others are related to the motivation of the donor, the approach to and evaluation of the donor, donation by strangers, the commercialization of donation, surrogate consent for donation, and the acceptance of minors as donors. The lack of clear consensus regarding these issues results in differences in practice, not only among countries but also among transplant centers. We believe that after an open debate, agreement on certain generally accepted principles can be achieved. Such an agreement would protect potential donors and recipients and would ensure the future of living donor kidney transplantation.     

Comparison of paired exchange kidney transplantations with living related kidney transplantations

Objective

Paired-exchange kidney transplantation (PETx) gains an importance because it is difficult to find suitable organs. The aim of this study was to compare biochemical and clinical parameters of PETx with those of living-related kidney transplantation (LRTx).

Method

The 57 PETx included 18 female and 39 male recipients among 1081 LRTx in 360 females and 721 males (N = 1138) whose operations were performed between November 21, 2008, and March 1, 2011. These two groups were compared for graft and patient survival, rejections, serum creatinine levels, glomerular filtration rates (GFRs), and other biochemical parameters.

Results

The PETx patients were older than the LRTx patients (45.4 ± 13.2 years versus 40.9 ± 13.5 years; P = .014). HLA mismatch was higher in the PETx group (4.7 ± 0.7 versus 3.56 ± 1.6; P = .000). First- and second-year serum creatinine and GFR values were similar between the two groups. Acute rejection episodes (PETx: 13/57; LRTx: 226/1081, P = .925), patient loss (0/57 versus 34/1081; P = .174) and graft loss (1/57 versus 55/1081; P = .257) were similar between the two groups.

Conclusion

Our study showed similar biochemical and clinical findings of PETx versus LRTx over 2 years posttransplantation.     

Improving HLA matching in living donor kidney transplantation using kidney paired exchange program

BackgroundThe inclusion of compatible pairs within kidney paired exchange programs has been described as a way to enhance these programs. Improved immunological matching for the recipient in compatible pair has been described to be a possible benefit.MethodsThe main purpose of our study was to determine if the introduction of compatible pairs in the Portuguese kidney paired exchange program would result in a better match for these patients, but also to assess if this strategy would increase the number of incompatible pairs with a possible match.We included 17 compatible pairs in kidney paired exchange pool of 35 pairs and performed an in-silico simulation determining HLA eplet mismatch load between the co-registered and matched pairs using HLA MatchMaker, version 3.0.ResultsOur study showed that the inclusion of fully HLA-A, -B, −DR mismatched compatible pairs within the national Portuguese KEP increased matched rate within ICP (0.71%) and improved HLA eplet matching within compatible pairs. 16 of 17 (94.12%) of the CP obtained one or more transplants possibilities and 13 (81.25%) would have been transplanted with significantly lower HLA class I and class II total and antibody-verified eplet mismatch load (83.9 ± 16.9 vs. 59.8 ± 12.2, P = .002 and 30.1 ± 5.5 vs. 21.2 ± 3.0, P = .003, respectively).ConclusionsThis strategy is a viable alternative for compatible pairs seeking a better matched kidney and Portuguese KEP program should allow them this possibility.     

Influence of educational programs on perceived barriers toward living donor kidney exchange programs

Living donor kidney exchange programs (LDKEPs) provide significant advantages toward addressing ABO and crossmatch incompatibility in living donor kidney transplantation, however, they have not yet realized their potential. The aim of this study was to examine the effect of an educational conference on perceived barriers toward living donor kidney transplantation and LDKEPs. METHODS: Between 2002 and 2004, a state-wide living donor/living donor kidney exchange program was established by the Ohio Solid Organ Transplant Consortium (OSOTC). Prior to initiating the OSOTC LDKEP, an educational conference was held and its effect on transplant professional attitudes toward LDKEP barriers were assessed prior to and following the conference using a questionnaire. Questions were answered using a Likert scale (LS) (1 = strongly agree, 5 = strongly disagree). RESULTS: Forty-eight participants completed questionnaires prior to and following the conference. The conference was judged to increase understanding of KEPs. The complementary web-based computer matching program was also felt to be an important component for the LDKEP. The conference did not affect the state of decision making regarding KEPs, however. Perceived barriers to LDKEPs not influenced by the educational conference included (1) concerns about donor travel costs, (2) concern about potential medical legal problems, (3) lack of perceived superiority of LDKEPs over desensitization protocols, and (4) concern about donation to strangers. Although numeric trends existed for each of these barriers, none were statistically significantly influenced by the education conference. CONCLUSIONS: These results suggest that interventions other than large scale educational conferences will be needed to address the barriers to LDKEP.     

Ethical issues in living renal donation

The widespread success of living renal transplantation has given the medical community both the opportunity and the responsibility of establishing social and ethical guidelines for the protection of donors and the treatment of recipients. While the prospects of treating more patients with organ transplant is exciting, the demand still far outpaces the supply. It is the responsibility of the transplant community and individual transplant centers to maintain a high level of integrity and ethical practice so that living renal transplantation can continue to be a viable and effective treatment for renal failure.     

Ethical issues surrounding high-risk kidney recipients: implications for the living donor

Evaulating patients for living kidney donor transplantation involving a recipient with significant medical issues can create an ethical debate about whether to proceed with surgery. Donors must be informed of the surgical risk to proceed with donating a kidney and their decision must be a voluntary one. A detailed informed consent should be obtained from high-risk living kidney donor transplant recipients as well as donors and family members after the high perioperative risk potential has been explained to them. In addition, family members need to be informed of and acknowledge that a living kidney donor transplant recipient with pretransplant extrarenal morbidity has a higher risk of a serious adverse outcome event such as graft failure or recipient death. We review 2 cases involving living kidney donor transplant recipients with significant comorbidity and discuss ethical considerations, donor risk, and the need for an extended informed consent.     

Ethical issues in using data from quality management programs

Since the advent of formal, data-driven quality improvement programs in health care in the late 1980s and early 1990s, there are have been questions raised about requirements for ethical committee review of quality improvement activities. A form of consensus emerged through a series of articles published between 1996 and 2007, but there is still significant variation among ethics review committees and individual project leaders in applying broad policies on requirements for committee review and/or written informed consent by participants. Recent developments in quality management, particularly the creation and use of multi-site disease registries, have raised new questions about requirements for review and consent, since the activities often have simultaneous research and quality improvement goals. This article discusses ways in which policies designed for local quality improvement projects and data bases may be adapted to apply to multi-site registries and research projects related to them.     

Allocation and matching in kidney exchange programs

Living donor kidney transplantation is the preferred treatment for patients suffering from end‐stage renal disease. To alleviate the shortage of kidney donors, many advances have been made to improve the utilization of living donors deemed incompatible with their intended recipient. The most prominent of these advances is kidney paired donation (KPD), which matches incompatible patient–donor pairs to facilitate a kidney exchange. This review discusses the various approaches to matching and allocation in KPD. In particular, it focuses on the underlying principles of matching and allocation approaches, the combination of KPD with other strategies such as ABO incompatible transplantation, the organization of KPD, and important future challenges. As the transplant community strives to balance quantity and equity of transplants to achieve the best possible outcomes, determining the right long‐term allocation strategy becomes increasingly important. In this light, challenges include making full use of the various modalities that are now available through integrated and optimized matching software, encouragement of transplant centers to fully participate, improving transplant rates by focusing on the expected long‐run number of transplants, and selecting uniform allocation criteria to facilitate international pools.     

Kidney exchange programs: attitudes of transplant team members toward living donation and kidney exchanges

INTRODUCTION: Several living donor kidney exchange programs (LDKEPs) have been established throughout the world; however, none have yet achieved the perceived substantial potential for increasing the number of living donor kidney transplants. Over the past 2 years, the Ohio Solid Organ Transplant Consortium (OSOTC) has developed and implemented an LDKEP with a complementary, robust web-based computerized matching program for living donor/recipient pairs. Prior to implementation of the OSOTC LDKEP, attitudes of transplant professionals from each of eight participating kidney transplant programs were surveyed to determined attitudes toward living donation and LDKEP and to identify potential barriers to LDKEP. The state of decision making toward LDKEP was also examined. METHODS: Transplant professionals were surveyed using an instrument designed to assess attitudes toward living donation and LDKEPs. Most questions were answered on a Likert scale (1 = strongly agree, 5 = strongly disagree). RESULTS: Respondents agreed that living donor transplantation should be encouraged (mean 1.17 +/- 0.6) and that the laparoscopic donor procedure was preferred (1.36 +/- 0.82). Respondents had largely read about KEPs (2.02 +/- 1.02) but had "thought about participating in KEPs" (2.57 +/- 1.26), or actively sought information (2.87 +/- 1.3) to lesser degrees. Despite this, significant indecisiveness existed regarding participation in LDKEPs (2.73 +/- 1.39). CONCLUSIONS: Transplant professionals are highly aware of LDKEPs. However, they remain indecisive about LDKEP participation. These results indicate that barriers exist in the transplant community toward LDKEP, and these must be defined to increase LDKEP acceptance and participation.     

Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors

With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible. Desensitization is the removal of circulating donor specific antibodies to prevent graft rejection. Regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ≥95% remain difficult to transplant with match rates as low as 15% in KPD pools. Desensitization has proved to be difficult in those with high antibody titers. A novel approach is the combination of both KPD and desensitization to facilitate compatible and successful transplantation. A highly sensitized patient can be paired with a better immunological match in the KPD pool and subsequently desensitized to a lesser degree. This article reviews the current progress in KPD and desensitization and their use as a combined therapy.     

Ethical considerations on kidney transplantation from living donors

Kidney transplantation from living donors is widely performed all over the world. Living nephrectomy for transplantation has no direct advantage for the donor other than increased self-esteem, but at least remains an extremely safe procedure, with a worldwide overall mortality rate of 0.03%. This theoretical risk to the donor seems to be justified by the socioeconomic advantages and increased quality of life of the recipient, especially in selected cases, such as pediatric patients, when living donor kidney transplantation can be performed in a preuremic phase, avoiding the psychological and physical stress of dialysis, which in children is not well tolerated and cannot prevent retarded growth. According to the Ethical Council of the Transplantation Society, commercialism must be prevented, not only for ethical but also medical reasons. The risks are too high not only for the donors, but also for the recipients, as a consequence of poor donor screening and evaluation with consequent transmission of human immunodeficiency virus or other infectious agents, as well as inappropriate medical and surgical management of donors and also of recipients, who are often discharged too early. Most public or private insurance companies are considering kidney donation a safe procedure without long-term impairment and, therefore, do not increase the premium, whereas recipient insurance of course should cover hospital fees for the donors. "Rewarded gifting" or other financial incentives to compensate for the inconvenience and loss of income related to the donation are not advisable, at least in our opinion. Our center does not perform anonymous living organ donation or "cross-over" transplantation.     

Five years of single-center experience with paired kidney exchange transplantation

INTRODUCTION: Due to the organ shortage, living donor transplantation has become a method to bridge the gap. Paired kidney exchange program (PKEP) is a viable method especially when there are incompatible related living donors. Even if there are still some unanswered questions, this program is current in some centers, and there appears to be a tendency to extend it in Europe. The aim of our study was to assess our results with PKEP after 5 years. METHODS: Between January 2001 and December 2005, we performed 56 living donor kidney transplantations using this method. We performed 26 kidney exchange procedures: 23 with two pairs, two with three pairs, and one with four pairs. Extensive preoperative work was necessarily to obtain equivalent pairs from the anatomic, functional, and immunological points of view. The same team performed all transplants. The mean recipient age was 35.59 years (range 29 to 44). Mean waiting time for a renal transplant was 33.27 months (range 11 to 87). RESULTS: At a median follow-up of 41 months (range 7 to 59), the rates of acute rejection and graft survival-19.64% and 98.21%-were similar to direct living donation-14.66% and 97.92%, respectively (P = .35 and .88, respectively). CONCLUSION: The paired kidney exchange program is a viable procedure medically and economically, which can be promoted in centers with a low deceased donor transplantation rate and a high number of incompatible related donors.     

Ethical and medical dilemmas in paid living kidney donor transplantation

Due to the shortage of deceased and genetically- or emotionally-related living donors, living unrelated paid donor (LURpD) kidney transplantation has been considered; however, this practice may result in medical, ethical and social dilemmas, induce organ trading (commodification), and even criminal activities. Commodification also risks undermining public trust in the transplant system and impeding the development of proper altruistic or deceased donor programs by ignoring altruism, volunteerism, and dignity. However, despite many objections by authoritative organizations, black market practices are involved in up to 10% of all transplants worldwide.The authors strongly discourage any payment or rewards for organ donation, and instead urge the governments of all countries to provide adequate and accessible kidney health care. However, it is an undeniable fact that paid-living donor transplantation is increasing despite all objections, disapprovals and regulations. We feel it as our responsibility not to ignore this uncertain and undesirable practice, but rather to underline the necessity for strict rules and prohibitions to minimize unacceptable medical, social and ethical risks as long as it exists. Furthermore, economic profit, be it direct or indirect, must not be the goal of those involved, and the employment of intermediaries must be avoided entirely. Additionally, the donor should be in a position where not donating has no detrimental effect on his/her future in any way (free agency).In our view, every country has the obligation and responsibility to provide adequate kidney health care and to make kidney transplantation accessible to those in need. This provision is key to stop transplant tourism and commercialization of kidney transplantation. The nephrology community has a duty to establish structures that optimize organ availability within strict ethical limits. The legal position of LURpD varies considerably worldwide. Strictly respecting each country's legislation and local values is mandatory to minimize medical and ethical risks and controversies.     

The benefit to waitlist patients in a national paired kidney exchange program: Exploring characteristics of chain end living donor transplants

Nondirected kidney donors can initiate living donor chains that end to patients on the waitlist. We compared 749 National Kidney Registry (NKR) waitlist chain end transplants to other transplants from the NKR and the Scientific Registry of Transplant Recipients between February 2008 and September 2020. Compared to other NKR recipients, chain end recipients were more often older (53 vs. 52 years), black (32% vs. 15%), publicly insured (71% vs. 46%), and spent longer on dialysis (3.0 vs. 1.0 years). Similar differences were noted between chain end recipients and non-NKR living donor recipients. Black patients received chain end kidneys at a rate approaching that of deceased donor kidneys (32% vs. 34%). Chain end donors were older (52 vs. 44 years) with slightly lower glomerular filtration rates (93 vs. 98 ml/min/1.73 m²) than other NKR donors. Chain end recipients had elevated risk of graft failure and mortality compared to control living donor recipients (both p < .01) but lower graft failure (p = .03) and mortality (p < .001) compared to deceased donor recipients. Sharing nondirected donors among a multicenter network may improve the diversity of waitlist patients who benefit from living donation.     

Motivations and outcomes of compatible living donor–recipient pairs in paired exchange

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan–Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50 years, p < .001), less often female (52% vs. 68%, p < .01), higher BMI (27 vs. 25 kg/m², p = .03), less frequently blood type O (36% vs. 80%, p < .001), and had higher eGFR (99 vs. 94 ml/min/1.73 m², p = .02), with a better LKDPI (median 7 vs. 22, p < .001). We observed no differences in graft failure or mortality. Compatible pairs made 280 additional transplants possible, many in highly sensitized recipients with long wait times. Compatible pair recipients derived several benefits from paired exchange, including better donor quality. Living donor pairs should receive counseling regarding all options available, including kidney paired donation. As more compatible pairs choose to enter exchange programs, consideration should be given to optimizing compatible pair and hard-to-transplant recipient outcomes.