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.

Creating Options for Difficult-to-match Kidney Transplant Candidates.

BACKGROUND: Most transplantation centers recognize a small patient population that unsuccessfully participates in all available, both living and deceased donor, transplantation programs for many years: the difficult-to-match patients. This population consists of highly immunized and/or ABO blood group O or B patients. METHODS: To improve their chances, Computerized Integration of Alternative Transplantation programs (CIAT) were developed to integrate kidney paired donation, altruistic/unspecified donation, and ABO and HLA desensitization. To compare CIAT with reality, a simulation was performed, including all patients, donors, and pairs who participated in our programs in 2015-2016. Criteria for inclusion as difficult-to-match, selected-highly immunized (sHI) patient were as follows: virtual panel reactive antibody >85% and participating for 2 years in Eurotransplant Acceptable Mismatch program. sHI patients were given priority, and ABO blood group incompatible (ABOi) and/or HLA incompatible (HLAi) matching with donor-specific antigen-mean fluorescence intensity (MFI) <8000 were allowed. For long-waiting blood group O or B patients, ABOi matches were allowed. RESULTS: In reality, 90 alternative program transplantations were carried out: 73 compatible, 16 ABOi, and 1 both ABOi and HLAi combination. Simulation with CIAT resulted in 95 hypothetical transplantations: 83 compatible (including 1 sHI) and 5 ABOi combinations. Eight sHI patients were matched: 1 compatible, 6 HLAi with donor-specific antigen-MFI <8000 (1 also ABOi), and 1 ABOi match. Six/eight combinations for sHI patients were complement-dependent cytotoxicity cross-match negative. CONCLUSIONS: CIAT led to 8 times more matches for difficult-to-match sHI patients. This offers them better chances because of a more favorable MFI profile against the new donor. Besides, more ABO compatible matches were found for ABOi couples, while total number of transplantations was not hampered. Prioritizing difficult-to-match patients improves their chances without affecting the chances of regular patients.

The optimal chain length for kidney paired exchanges: an analysis of the Dutch program.

Living donor kidney exchange programs offer incompatible donor-recipient pairs the opportunity to be transplanted. To increase the number of these transplants, we examined in our actual donor-recipient couples how to reach the maximum number of matches by using different chain lengths. We performed 20 match procedures in which we constructed four different chain lengths: two, up to three, up to four and unlimited. The actual inflow and outflow of donor-recipient couples for each run were taken into consideration in this analysis. The total number of matched pairs increased from 148 pairs for only two-way exchanges to 168 for three-way exchanges. When a chain length of 4 was allowed five extra couples could be matched over a period of 5 years. Unlimited chain length did not significantly affect the results. The optimal chain length for living donor kidney exchange programs is 3. Longer chains with their inherent logistic burden do not lead to significantly more transplants.

Paired kidney donations to expand the living donor pool.

INTRODUCTION: The shortage of available deceased donors and the longer kidney transplant waiting lists in many countries around the world have placed greater emphasis on living donation (LD) as a means of meeting demand for transplantation in patients with end-stage kidney disease (ESKD). METHODS AND RESULTS: Increased LD rates are also driven by less invasive approaches to donor nephrectomy and by the excellent long-term results. LD kidney transplant outcomes are equivalent, if not superior, to those from deceased donors, even when donor and recipient are not genetically related, as is the case with spousal donations, the most frequent cohort of LD. Approximately 30% of willing and otherwise appropriate kidney donor/recipient pairs are biologically incompatible and do not proceed to live donor transplantation. In recent years, a number of strategies have been introduced to expand living donation programs beyond the classical direct donation, to overcome immunological barriers of blood group or HLA sensitization of recipients. New strategies in LD include paired kidney exchange (PKE), altruistic donation, altruistic donor chains and list exchange programs. Other alternative programs are desensitization and transplantation across the blood-type barrier. Regular PKE programs operate nationally in The Netherlands and the United Kingdom, or regionally in South Korea, Romania, the United States and Australia. CONCLUSIONS: If PKE were performed routinely using 2-way or 3-way PKE and altruistic donor chains, the rate of kidney transplants could increase by between 7% and 10%.

Strategies to expand the living donor pool for kidney transplantation.

Structural shortage of deceased donor kidneys for transplantation has resulted in the expansion of living donation programs. A number of possibilities are now being explored, since it became clear that donors do not need to be genetically related to their recipients. Apart from classical direct donation we now conduct paired exchange, list exchange, altruistic donation and domino paired exchange programs. Other alternative programs are desensitization and transplantation across the blood type barrier. The purpose of this article is to give a general view of all optimizing living donation programs by reviewing the literature. First we describe logistic solutions, thereafter the more intensive medical treatments. We observed a wide variation in clinical experiences with living donation dependent on local jurisdiction, culture and customs. Professionals disagree on various ethical issues inherent to alternative programs. In our opinion logistic solutions like paired exchange, list exchange and altruistic donation programs are to be preferred over the more medical demanding programs e.g. desensitization and transplantation across the blood type barrier.

A highly efficient living donor kidney exchange program for both blood type and crossmatch incompatible donor-recipient combinations.

BACKGROUND: Lack of deceased donors for kidney transplant patients in the Netherlands encouraged alternative options to expand the living donor pool for recipients who have a willing donor but cannot donate directly because of a positive crossmatch or ABO blood type incompatibility. A national donor kidney exchange was considered as a possible solution. METHODS: From January 2004 until June 2006, 146 couples from seven kidney transplantation centers were enrolled and participated in 10 match procedures. The Dutch Transplant Foundation was responsible for the allocation and the National Reference Laboratory for Histocompatibility in Leiden performed all the serological crossmatches. RESULTS: For 72 out of the 146 (49%) donor-recipient combinations, a match was found. The success rate in the positive crossmatch group was significantly (P = 0.0015) higher than in the ABO-incompatible group (44/69 vs. 28/77); median panel reactive antibodies of the matched recipients in the positive crossmatch group was 38% (0-100) and in the ABO-incompatible group 0% (0-27; P < 0.001). We were least successful for ABO blood type incompatible pairs with blood type O recipients, but for 9/53 (17%) there were possibilities. These nine blood type incompatible pairs were coupled to nine positive crossmatch pairs, which reflects the efficiency of combining the two categories of donor-recipient combinations into one program. CONCLUSION: The donor kidney exchange program in the Netherlands, in which all seven kidney transplantation centers participated, proved to be a successful program to expand the number of living donor kidney transplantations.

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 "donation by strangers" on the motivation and willingness of donor-patient couples, the issue of anonymity, the loss of the possibility of "medical excuses" 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.

Coordinating unspecified living kidney donation and transplantation across the blood-type barrier in kidney exchange.

BACKGROUND: This article studies multicenter coordination of unspecified living kidney donation and transplantation across the blood-type barrier in kidney exchange. Important questions are whether such coordination should use domino paired donation or non simultaneous extended altruistic donor chains, what the length of the segments in such chains should be, when they should be terminated, and how much time should be allowed between matching rounds. Furthermore, it is controversial whether the different modalities should be coordinated centrally or locally and independently. METHODS: Kidney exchange policies are simulated using actual data from the Dutch national kidney exchange program. Sensitivity analysis is performed on the composition of the population, the time unspecified and bridge donors wait before donating to the wait list, the time between matching rounds, and donor renege rates. RESULTS: Central coordination of unspecified donation and transplantation across the blood-type barrier can increase transplants by 10% (PG0.001). Especially highly sensitized and blood type O patients benefit. Sufficient time between matching rounds is essential: three-monthly exchanges result in 31% more transplants than weekly exchanges. Benefits of non simultaneous extended altruistic donor chains are limited in case of low numbers of highly sensitized patients and sufficient unspecified donors. Chains are best terminated when no further segment is part of an optimal exchange within 3 months. CONCLUSIONS: There is clear synergy in the central coordination of both unspecified donation and transplantation across the blood-type barrier in kidney exchange. The best configuration of a national program depends on the composition of the patient Y donor population.

Eight years of outcomes of the Dutch Living Donor Kidney Exchange Program.

In January 2004, the Dutch transplant centers agreed on a protocol for a national Living Donor Kidney Exchange Program for ABO blood type incompatible and positive cross match donor-recipient pairs. Here, we report the results of that program. All transplants performed within the Living Donor Kidney Exchange Program between January 2004 and December 2011 were analysed. We collected demographic data of recipients and donors. Univariate and multivariate Cox proportional hazard analyses were performed, including recipient age, donor age, and reason for participation in the exchange program. We studied overall uncensored survival and graft survival censored for death in both ABO blood type incompatible and positive cross match groups. We enrolled 472 donor-recipient combinations, consisting of 269 ABO blood type incompatible pairs and 203 positive cross match pairs. In the end, we performed 187 kidney transplants (40% of those enrolled) with 83 ABO blood type incompatible and 104 positive cross match pairs. Most of the transplanted recipients (119/187, 64%) had an age difference of less than 5 years with their original incompatible donors. The age differences with their actual donors varied widely, but the number of recipients with a donor > 5 years older was comparable to the number of recipients with a donor > 5 years younger. In the multivariate Cox analysis, age as a continuous variable was found to have a significant influence on graft failure. Nevertheless, the 5-year uncensored survival (85%) and the graft survival censored for death (89%) were excellent and comparable to the results of direct living donation. No differences were found between the ABO incompatible and the positive cross match groups. The Dutch Living Donor Kidney Exchange Program has a high transplant rate of 40%, with excellent 5 year graft survival.

Alternatives for unsuccessful living donor kidney exchange pairs.

UNLABELLED: 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. METHODS: Data on registration, computerized matching, cross matching, and transplantations within or outside the program were collected. RESULTS: 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. CONCLUSION: 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.

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.

Hurdles, barriers, and successes of a national living donor kidney exchange program.

BACKGROUND: Living donor kidney exchange is now performed in several countries. However, no information is available on the practical problems inherent to these programs. Here, we describe our experiences with 276 couples enrolled in the Dutch program. METHODS: Our protocol consists of five steps: registration, computerized matching, crossmatching, donor acceptation, and transplantation. We prospectively collected data of each step of the procedure. RESULTS: Of the 276 registered pairs we created 183 computer-matched combinations. However, 62 of 183 recipients proved to have a positive crossmatch with their new donor, which was not predicted by the screening results of the recipient centers. Alternative solutions were found for 39 couples, resulting in a total of 160 new combinations with negative crossmatches. Thereafter, because of 22 individual clinical problems, the exchange procedure had to be discontinued for 51 couples while only for 19 of them alternative solutions were found. At the end of day, 128 patients had received exchange kidneys, 55 were transplanted outside the program, 59 are still on the crossover waitlist, and 34 had left the program for medical or psychological reasons. CONCLUSION: A living donor kidney exchange program is a dynamic process. Many clinical hurdles and barriers are encountered that for a large part were not foreseen but should be taken into account when programs are initiated based on computer simulations. Success is dependent on a flexible organization able to create alternative solutions when problems arise. Centralized allocation and crossmatch procedures are instrumental in this respect.

A flexible national living donor kidney exchange program taking advantage of a central histocompatibility laboratory: the Dutch model.

The shortage of deceased donor kidneys for transplantation has resulted in the expansion of living donation programs. A number of possibilities have been explored, since it became clear that donors do not need to be genetically related to their recipients. Apart from classical direct donation, other options such as paired exchange, list exchange, altruistic donation and domino paired exchange programs have been implemented. In the Netherlands, patients who cannot be transplanted with their potential living donor because of ABO blood group incompatibility or a positive crossmatch, have the option to participate in a national paired kidney exchange program. The practical issues related to this program are described. The 5-years experience with the Dutch kidney exchange program is very positive as, so far, 42% of the recipients included have been transplanted. Recommendations are given for a successful implementation of a common kidney exchange program of different transplantation centers focusing on the advantage of a central histocompatibility laboratory.

The implementation of a kidney exchange program does not induce a need for additional psychosocial support.

The Dutch kidney exchange donation program started in January 2004. A literature review has shown that several factors of the exchange program could influence the psychological well being of participants, such as the loss of the possibility of a 'medical excuse' for unwilling donors and the issue of anonymity. However, these factors have not been the subject of empirical study yet. We therefore studied these factors to determine whether additional psychosocial support is necessary for donors and recipients in the Dutch kidney exchange program. We used structured interviews for all 48 donors and recipients that had undergone exchange donation/transplantation in 2004. A psychologist interviewed the participants before and 3 months after transplantation. We included a comparison group of 48 donors and recipients participating in the regular living kidney donation program. Donors did not experience additional pressure to donate due to the exchange donation. Most participants (69%) preferred anonymity between the couples. Ten percentage needed additional emotional support. In this respect the exchange group did not differ from the comparison group. We conclude that the psychosocial support offered to exchange couples can be comparable with the support normally offered to participants in the regular living kidney donation program.

One donor, two transplants: willingness to participate in altruistically unbalanced exchange donation.

Kidney exchange donation programs offer a good solution to help patients with a willing, but incompatible living kidney donor. Literature shows that blood type O patients are less likely to be selected for transplantation within a living exchange donation program. 'Altruistically unbalanced donation' could help these blood type O patients: one donor-recipient pair is incompatible (e.g. A-donor > O-recipient) and the other pair is compatible, but not identical (e.g. O-donor > A-recipient). Exchanging these kidneys would result in two compatible living donor kidney transplants. We studied whether compatible pairs would be willing to participate in such procedure. We included 96 living kidney donors and recipients in our study. These donors and recipients could be divided into two groups: (i) donors and their direct recipients (n = 48), and (ii) paired exchange donors and their intended recipients (n = 48). All were asked whether they would be willing to participate in altruistically unbalanced exchange donation, as long as direct donation was also an option. We found no group differences. We found that one third of the donors and recipients are willing to participate in altruistically unbalanced kidney exchanges. Therefore this form of donation may be a feasible addition to already existing living kidney exchange programs.

The Dutch national living donor kidney exchange program.

The wait time for deceased-donor kidney transplantation has increased to 4-5 years in the Netherlands. Strategies to expand the donor pool include a living donor kidney exchange program. This makes it possible that patients who cannot directly receive a kidney from their intended living donor, due to ABO blood type incompatibility or a positive cross match, exchange donors in order to receive a compatible kidney. All Dutch kidney transplantation centers agreed on a common protocol. An independent organization is responsible for the allocation, cross matches are centrally performed and exchange takes place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are scheduled simultaneously. Sixty pairs participated within 1 year. For 9 of 29 ABO blood type incompatible and 17 of 31 cross match positive combinations, a compatible pair was found. Five times a cross match positive couple was matched to a blood type incompatible one, where the recipients were of blood type O. The living donor kidney exchange program is a successful approach that does not harm any of the candidates on the deceased donor kidney waitlist. For optimal results, both ABO blood type incompatible and cross match positive pairs should participate.