Marry de Klerk

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.

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 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.

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.

Ingredients for a successful living donor kidney exchange program

A simple solution for all kidney patients with a willing but incompatible living donor, because of a positive cross match or an ABO blood type incompatibility, is living donor kidney exchange (1). Over the last two decades, several centers in various countries embarked on these programs (2). In South Korean the first procedure was performed in 1991, in Switzerland a single exchange took place in 1999, while individual centers in the United States, The Netherlands, and Canada followed in 2000, 2003, and 2005, respectively. However, not all these initiatives have resulted in regular programs. Most single centers are not able to accrue enough candidates for efficient exchange of both easy and difficult-to-match pairs on a permanent basis. For that purpose collaboration with other centers is essential. Indeed, Segev et al. in this issue (3) calculated that by expansion of a paired kidney exchange (PKE) program to a national level more difficult to match couples could be helped. Along the same line, Basu et al. proposed PKE to improve HLA-matching and thus transplantation outcomes in India (4). In the Netherlands with a population of 16.4 10 inhabitants we started a national exchange program in 2004. All seven transplant centers work according to a common protocol for the evaluation of the donor, while we agreed on only four simple rules. Registration of donor/acceptor combinations can take place four times a year only if donor and acceptor are medical suitable for donation and transplantation. Allocation is the responsibility of an independent organization, the Dutch Transplant Foundation. Because computerized matching will result in huge numbers of possible combinations of donor-recipient pairs, allocation criteria are necessary. Thus, our computer program selects the best possible combinations on six preset conditions: (1) a maximum number of matched couples, (2) blood type identical before blood type compatible matches, (3) most difficult to match patients (highly sensitized recipients) first, based on HLA match probability, (4) short chains preferred (e.g. rather two doublets than one quartet), (5) couples distributed over multiple centers, (6) wait time calculated from the first day of dialysis. PKE is for many patients the best if not the only option and to be preferred over dialysis. Therefore, we kept our algorithm as simple as possible without too many complicating parameters, for example, donor age, gender, CMV sera status, renal function, or number of HLA mismatches. The third rule is that the national HLA reference laboratory performs all the cross matches between the new donor and the recipient. And finally surgical procedures will take place on the same moment and not the kidney will be transported but the donor travels to the recipient center to ensure minimal logistic problems and to keep ischemia times as short as possible. With these four important rules we now run a national program for four and half years. From January 2004 to June 2008, we registered 143 pairs with blood type incompatibility and 133 pairs with a positive crossmatch. We have now performed 18 match runs with a median input of 14 new pairs (range, 7–22 pairs) per match run and a median number of couples participating per match run of 47 (range, 16 – 66 pairs) which is still increasing (Fig. 1). In the ABO blood type incompatible group almost 70% (99 of 143) had blood type O recipients. Median PRA in the positive cross match group was 46% (2–100). We found new match combinations for 159 of 276 (58%) registered couples. Easy-tomatch couples with blood type A recipients and blood type B donors or vice versa had a 85% success rate. However, also the positive cross match couples with a median PRA of 46% could successfully be matched in 74% of the cases. Combining blood type incompatible and positive cross match donorrecipient pairs in one program increased our success rate and Department of Internal Medicine-Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Dutch Transplant Foundation, Leiden, The Netherlands. Address correspondence to: Marry de Klerk, S.W., Erasmus Medical Center Rotterdam, Department of Internal Medicine – Transplantation, Office D 408, P.O. Box 2040, 3000 CA Rotterdam The Netherlands. E-mail: marry.deklerk@erasmusmc.nl Received 31 January 2008. Revision requested 3 March 2008. Accepted 20 May 2008. Copyright

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.

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 nonsimultaneous 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 waitlist, 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% (P<0.001). 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 nonsimultaneous 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–donor population.