The Dutch Living Donor Kidney Exchange Program

Kidney transplantation is the optimal option for patients with an end-stage renal disease. The first successful transplantation with a living genetically related donor has been performed since 26 October 1954, when an identical twin transplant was performed in Boston. In the years that followed, efforts to enable non-twin transplants unfortunately failed because effective immunosuppression was not yet available. It took until the early sixties after the discovery of azathiopirine that also deceased donor kidney transplantations became possible. In the eighties of the last century the wait time for a kidney transplant was approximately one year. Since that time the success rate of organ transplantation has significantly improved which attracted large numbers of transplant candidates. As the number of deceased organ donors did not increase, the wait time on the list steadily grew and at the moment patients in most Western countries face wait times up to 5 years before a deceased donor kidney is offered. Unfortunately an increasing proportion of them will never be transplanted because their clinical situation deteriorates to such an extent that they are delisted or die on the wait list. For the Netherlands we estimate that this proportion is approximately 30%. A strategy to expand the kidney donor pool includes the use of non-heart beating (NHB) donors. Educational programs in the Netherlands have resulted in an increase in the number of kidney transplants derived from NHB donors from almost 20% in the year 2000 to 43% in 2004, while in the years that followed the numbers of NHB donors stabilized. So the NHB donors have not led to expansion of the deceased kidney donor pool. Possibly substitution from heart beating to non heart beating donation procedures took place, resulting from pressure on the facilities of intensive care units. In the Netherlands, it has been suggested that the main reason for our failure to increase the number of deceased organ donors is the lack of donor detection. This is certainly not the case; both in 2005 and in 2006 almost all potential donors in the Netherlands (96%) were recognized as such and for the vast majority (86%) our national donor registry was consulted. The problem is not donor detection but the high refusal rate by the next of kin, which is inherent to our legal system. Our organ donation act dictates an opt-in system, and therefore all adult citizens are asked to register their consent for the use of their organ for transplantation purpose after death. In the Netherlands approximately 25% of the adults are now registered as potential donors, 15% have explicitly refused and thus for 60% it remains unknown. Especially in case of potential donors of the latter category high refusal rates up to 70% haven been found. Apparently next of kin argue that while the possibility was given to everybody to register as donor, their relative did not do so, therefore they are unaware of consent and thus reluctant to give permission for donation. We feel that an opt-out organ donation system would be very much helpful to expand the deceased kidney donor pool. However, we are aware that even if all potential deceased donors became actual donors, there still would be a shortage of donor kidneys. Therefore the use of kidneys from living donors is an obvious way to go. These transplants result in a superior unadjusted graft survival compared to deceased donor kidneys. It has been calculated that the difference in 10 years survival between living and deceased donor kidney transplantation is 34 %

Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation

Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteristics? Between 2000 and 2014, 1232 living donor transplantations have been performed. In conventional and ABO-incompatible transplantation the willing donor becomes an actual donor for the intended recipient. In kidney-exchange and domino-donation the donor donates indirectly to the intended recipient. The relationship between the donor and intended recipient was studied. There were 935 conventional and 297 alternative program transplantations. There were 66 ABO-incompatible, 68 domino-paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting list recipients (n=101) were excluded as they did not bring a living donor. 1131 couples remained of whom 196 participated in alternative programs. Genetically unrelated donors (486) were primarily partners. Genetically related donors (645) were siblings, parents, children, and others. Compared to genetically related couples, almost three times as many genetically unrelated couples were incompatible and participated in alternative programs (P<0.001). 62% of couples were genetically related in the conventional donation program versus 32% in alternative programs (P<0.001). Patient and graft survival were not significantly different between recipient programs. Alternative donation programs increase the number of transplantations by enabling genetically unrelated donors to donate

Starting a Crossover Kidney Transplantation Program in The Netherlands: Ethical and Psychological Considerations

On April 15th, 2003, the first crossover kidney transplantation took place in The Netherlands. In September of the same year, a national database was established to facilitate kidney exchange between two donor-recipient couples. During 2004, kidneys from living donors will be exchanged between the seven university medical centers in The Netherlands. One of the conditions for successfully implementing this program was the need to address the ethical and psychologic implications involved. In this article we will discuss the ethical and psychologic considerations that are accompanying the practical preparations for the first Dutch crossover transplantation program. We identified five topics of interest: the influence of &quot;donation by strangers&quot; on the motivation and willingness of donor-patient couples, the issue of anonymity, the loss of the possibility of &quot;medical excuses&quot; for unwilling donors, the view that crossover is a first step to commercial organ trade, and the interference with existing organ donation programs. We concluded that whether viewed separately or in combination, these issues do not impede the efficient organization of a crossover program or raise worrying ethical issues. Key Words: Ethics, psychology, crossover transplantation, kidney exchange program. 2004;78: 194 -197) T he Netherlands has a population of 16 million. Approximately 375 to 425 kidneys per year are transplanted from cadaver donors. In addition to cadaver transplants, approximately 200 kidneys from living donors were transplanted during 2003. Although the growing number of available living donors helps prevent the waiting lists from growing further, there are not enough kidneys available to help the 1,300 patients already on the waiting list. After starting dialysis, kidney patients have an average waiting time of 4 years before a kidney becomes available. In the meantime, their health status declines. Currently, the mortality rate of patients on dialysis is approximately 20% per year (1). (Transplantation Living organ donation by family or friends offers an opportunity to reduce the long waiting lists. However, in a third of these cases, the transplantation cannot take place because of ABO incompatibility or donor-specific sensitization (2). A crossover transplantation program offers new hope. The program provides a lifesaving opportunity when a donor cannot give his or her kidney to his or her recipient. If another donor-recipient couple experiences the same problem, the kidneys can be exchanged. In South Korea, such a crossover kidney exchange program has been operating successfully for more than 10 years (3). The United States also has experience with &quot;kidney swapping&quot; (4). In Europe, however, crossover transplantations have been attempted only once in Switzerland, in Romania, and in Rotterdam. This conservative European attitude is in part explained by concerns surrounding the ethical and psychologic implications of crossover transplantation. When a crossover program was initiated in The Netherlands, it was agreed that these concerns should be addressed. A multidisciplinary research effort was conducted to determine the most prominent psychologic and ethical issues that surround crossover kidney exchange and to propose practical solutions. We identified five topics of interest: (1) the influence of &quot;donation by strangers&quot; on the motivation and willingness of donor-patient couples; (2) the issue of anonymity; (3) the loss of the possibility of &quot;medical excuses&quot; for unwilling donors; (4) the view that crossover might be the first step to commercial organ trade; and (5) the interference with existing organ donation programs. Next we describe these five topics in detail and suggest practical solutions. Living Organ Donation by Strangers When discussing the ethical and psychologic issues of a crossover transplantation program, a prominent issue is the possibility of a difference in motivation and willingness of kidney donors and recipients compared with the attitudes of those involved in a direct living donation program. At first glance, crossover donation between two couples is not significantly different from direct living kidney donation. The motivation of the donor is the same: helping a friend or a family member by giving a kidney. The result for the patient is equivalent as well: He or she receives the much needed organ. Furthermore, the medical impact for the four people involved is the same as for the two direct living kidney donors. Psychologically, however, it might matter for those involved whethe

On chain lengths, domino-paired and unbalanced altruistic kidney donations.

Kidney transplantations with living related and unrelated donors are the optimal option for patients with end-stage renal disease. For patients with a willing--but blood-type or HLA incompatible donor--a living-donor kidney exchange program could be an opportunity. In Asia, the United States and Europe, kidney exchange programs were developed under different conditions, with different exchange algorithms, and with different match results. The easiest way to organize a living-donor kidney exchange program is to enlist national or regional cooperation, initiated by an independent organization that is already responsible for the allocation of deceased donor organs. For logistic reasons, the optimal maximum chain length should be three pairs. To optimize cross-match procedures a central laboratory is recommended. Anonymity between the matched pairs depends on the culture and logistics of the various countries. For incompatible donor-recipient pairs who have been unsuccessful in finding suitable matches in an exchange program, domino-paired kidney transplantations triggered by Good Samaritan donors is the next alternative. To expand transplantations with living donors, we advise integrating such a program into a national exchange program under supervision of an independent allocation authority. If no Good Samaritan donors are available, an unbalanced kidney paired-exchange program with compatible and incompatible pairs is another strategy that merits future development.</p

Alternatives for unsuccessful living donor kidney exchange pairs.

Living donor kidney exchange has become an efficient solution for recipients with incompatible donors. Here we describe the fate of all patients that were enrolled in our program during 2004-2010. Data on registration, computerized matching, cross matching, and transplantations within or outside the program were collected. Between January 2004 and December 2010, 422 pairs were registered. To create new combinations a match procedure was run 28 times with a median input of 14 (7-22) new pairs and a median of 55 (16-92) participating pairs. Matches were found for 127/185 (69%) cross match-incompatible pairs and 91/237 (38%) ABO-incompatible pairs. 141 of the 218 matched pairs successfully donated and received kidneys in exchange. There were 77 transplants cancelled for medical or psychological reasons, and an alternative solution was found for 26 of these. So in total 167 (141 + 26) patients received a transplant. Of the remaining 51 cancelled transplants, 26 pairs dropped out, 22 patients found an alternative transplantation outside the program and 3 are still waiting. For the 204 unmatched couples, 46 are still in the program while 34 others dropped out, and 124 found an alternative living kidney donor. After 7 years, 39% of participants received a kidney within the exchange program, 35% were transplanted outside the program, 14% of the pairs were delisted and 12% are still waiting. Among the 146 patients who received a kidney outside the program, 47 were transplanted with a deceased donor kidney, 21 found another donor, 37 received an ABO-incompatible transplant and 41 were transplanted in a domino-paired procedure triggered by an non-directed donor. In the 7 years of our Living Donor Kidney Exchange Program 313/422 (74%) of the participating patients were transplanted. Approximately half of them (167/313, 53%) received a kidney through the exchange program, while 47 (15%) received a deceased donor kidney and 99 (32%) were transplanted through other living donation programs. The exchange program proved to be highly successful not only in its direct results but also indirectly by triggering alternative solutions.</p

On chain lengths, domino-paired and unbalanced altruistic kidney donations.

Kidney transplantations with living related and unrelated donors are the optimal option for patients with end-stage renal disease. For patients with a willing--but blood-type or HLA incompatible donor--a living-donor kidney exchange program could be an opportunity. In Asia, the United States and Europe, kidney exchange programs were developed under different conditions, with different exchange algorithms, and with different match results. The easiest way to organize a living-donor kidney exchange program is to enlist national or regional cooperation, initiated by an independent organization that is already responsible for the allocation of deceased donor organs. For logistic reasons, the optimal maximum chain length should be three pairs. To optimize cross-match procedures a central laboratory is recommended. Anonymity between the matched pairs depends on the culture and logistics of the various countries. For incompatible donor-recipient pairs who have been unsuccessful in finding suitable matches in an exchange program, domino-paired kidney transplantations triggered by Good Samaritan donors is the next alternative. To expand transplantations with living donors, we advise integrating such a program into a national exchange program under supervision of an independent allocation authority. If no Good Samaritan donors are available, an unbalanced kidney paired-exchange program with compatible and incompatible pairs is another strategy that merits future development.</p

Alternatives for unsuccessful living donor kidney exchange pairs.

Living donor kidney exchange has become an efficient solution for recipients with incompatible donors. Here we describe the fate of all patients that were enrolled in our program during 2004-2010. Data on registration, computerized matching, cross matching, and transplantations within or outside the program were collected. Between January 2004 and December 2010, 422 pairs were registered. To create new combinations a match procedure was run 28 times with a median input of 14 (7-22) new pairs and a median of 55 (16-92) participating pairs. Matches were found for 127/185 (69%) cross match-incompatible pairs and 91/237 (38%) ABO-incompatible pairs. 141 of the 218 matched pairs successfully donated and received kidneys in exchange. There were 77 transplants cancelled for medical or psychological reasons, and an alternative solution was found for 26 of these. So in total 167 (141 + 26) patients received a transplant. Of the remaining 51 cancelled transplants, 26 pairs dropped out, 22 patients found an alternative transplantation outside the program and 3 are still waiting. For the 204 unmatched couples, 46 are still in the program while 34 others dropped out, and 124 found an alternative living kidney donor. After 7 years, 39% of participants received a kidney within the exchange program, 35% were transplanted outside the program, 14% of the pairs were delisted and 12% are still waiting. Among the 146 patients who received a kidney outside the program, 47 were transplanted with a deceased donor kidney, 21 found another donor, 37 received an ABO-incompatible transplant and 41 were transplanted in a domino-paired procedure triggered by an non-directed donor. In the 7 years of our Living Donor Kidney Exchange Program 313/422 (74%) of the participating patients were transplanted. Approximately half of them (167/313, 53%) received a kidney through the exchange program, while 47 (15%) received a deceased donor kidney and 99 (32%) were transplanted through other living donation programs. The exchange program proved to be highly successful not only in its direct results but also indirectly by triggering alternative solutions.</p

Increasing Kidney-Exchange Options Within the Existing Living Donor Pool With CIAT: A Pilot Implementation Study

Computerized integration of alternative transplantation programs (CIAT) is a kidney-exchange program that allows AB0- and/or HLA-incompatible allocation to difficult-to-match patients, thereby increasing their chances. Altruistic donors make this available for waiting list patients as well. Strict criteria were defined for selected highly-immunized (sHI) and long waiting (LW) candidates. For LW patients AB0i allocation was allowed. sHI patients were given priority and AB0i and/or CDC cross-match negative HLAi allocations were allowed. A local pilot was established between 2017 and 2022. CIAT results were assessed against all other transplant programs available. In the period studied there were 131 incompatible couples; CIAT transplanted the highest number of couples (35%), compared to the other programs. There were 55 sHI patients; CIAT transplanted as many sHI patients as the Acceptable Mismatch program (18%); Other programs contributed less. There were 69 LW patients; 53% received deceased donor transplantations, 20% were transplanted via CIAT. In total, 72 CIAT transplants were performed: 66 compatible, 5 AB0i and 1 both AB0i and HLAi. CIAT increased opportunities for difficult-to-match patients, not by increasing pool size, but through prioritization and allowing AB0i and “low risk” HLAi allocation. CIAT is a powerful addition to the limited number of programs available for difficult-to-match patients

Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation

Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteristics? Between 2000 and 2014, 1232 living donor transplantations have been performed. In conventional and ABO-incompatible transplantation the willing donor becomes an actual donor for the intended recipient. In kidney-exchange and domino-donation the donor donates indirectly to the intended recipient. The relationship between the donor and intended recipient was studied. There were 935 conventional and 297 alternative program transplantations. There were 66 ABO-incompatible, 68 domino-paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting list recipients (n = 101) were excluded as they did not bring a living donor. 1131 couples remained of whom 196 participated in alternative programs. Genetically unrelated donors (486) were primarily partners. Genetically related donors (645) were siblings, parents, children, and others. Compared to genetically related couples, almost three times as many genetically unrelated couples were incompatible and participated in alternative programs (P < 0.001). 62% of couples were genetically related in the conventional donation program versus 32% in alternative programs (P < 0.001). Patient and graft survival were not significantly different between recipient programs. Alternative donation programs increase the number of transplantations by enabling genetically unrelated donors to donate