Paired Exchanges Should Be Part of the Solution to Abo Incompatibility in Living Donor Kidney Transplantation

An anticipated result of our recent publication (1) has been an increased awareness and interest in living donor kidney exchange programs. The considerations raised in the letter by Terasaki et al.(2) serve to focus attention on a few of the issues regarding living donor kidney exchange programs. Several misconceptions, however, exist in the letter that warrant clarification. It is essential that the intention of our proposed pilot study be understood so that the protocol design not be misinterpreted. The proposed study was intended as a pilot study, with primary goals to show feasibility and to examine the ethical and psychological issues raised by living donor kidney exchanges. The proposed pilot study was not restricted to spousal transplants. We believe that kidney exchange programs should be open to all potential living donor pairs, both spousal and nonspousal transplants. Terasaki et al. claim that exchanges based on ABO incompatibilities "would have to be based on a computerized nationwide pool" (2). This claim may be based on the small number of potential spousal exchange pairs. If living donor exchanges are performed for both spousal and nonspausal donor-recipient pairs, we believe that regional bases for exchanges will be adequate. Our proposal for a pilot study was deliberately restrictive in its inclusion criteria (i.e., restricting enrollment to donors and recipients of A and B blood groups), thereby excluding O blood group donors and their recipients. To participate in a living donor kidney exchange program, O blood group recipients require an O donor from another donor-recipient pair. Because O donors can donate universally, the participation of O donors (and their potential recipients) requires a level of altruism greater than that required of A or B blood group donors (Table 1). Thus, O blood group donors (and their recipients) experience an "unbalanced altruism" as they must relinquish their ability to give to (and receive from) their genetically or emotionally related recipient. Similarly, AB recipients and their donors (because AB recipients can receive any ABO kidney), like O donors (who can donate to any ABO blood group recipient), also would experience unbalanced altruism.Table 1: Altruism balance in living donor kidney exchanges for ABO incompatibilityFor the purposes of our pilot study, we excluded O blood group recipients(i.e., the largest group of potential recipients). Although elimination of O blood group recipients significantly reduces the number of potential subjects for entry, their exclusion was necessary to avoid adding another layer of complexity to the ethical considerations. We believe that altruistically unbalanced living donor kidney exchange transplants should be considered only after significant experience has been gained with altruistically balanced transplants and only if broad consensus emerges that such requests are not excessively coercive (3). Although Terasaki et al. (2) did not specify how the ABO donor-recipient pair frequencies were computed, we assume that they were computed using ABO blood group frequencies in the U.S. population. A closer look at the data (Table 1) indicate that 8% (3% for A to B plus 5% for B to A) of all potential ABO blood group donor-recipient pairs are eligible for kidney donor exchanges. The number of exchanges that can be performed is limited by the smaller frequency (3% A to B). Therefore, since two transplants are performed with each exchange, a total of 6% (3% A to B plus 3% B to A) of living donor transplants can benefit from such a kidney exchange program. Although the chances of ABO compatibility among individual donor-recipient pairs can be easily computed, computation of the chances of benefiting by an altruistically balanced living donor kidney exchange requires more complex calculation, as several factors modify the result. The presence of multiple donors for each recipient and the fact that a donor can be excluded for many reasons are just two examples of complicating factors. A maximal estimate of the potential impact of living donor exchanges can be obtained (using the frequencies in Table 1) by assuming that each recipient has only one potential donor. In 1995, 3212 living donor kidney transplants were performed in the United States and were therefore ABO-compatible(4). Assuming that 64% of all potential ABO-compatible donor-recipient pairs were ABO-compatible, 36% would be ABO-incompatible (sum of the total frequencies in Table 1). It follows that 1807 ABO-incompatible donor-recipient pairs would not have received transplants in 1995 (given the assumption that each recipient has only one potential donor). Therefore, as a maximal estimate, 22% of 1807, i.e., 397, ABO-incompatible donor-recipient pairs could have been eligible for participation in an altruistically balanced exchange program. In our program, between 10% and 20% of living donor transplants cannot be performed because of ABO incompatibility. We believe, therefore, that approximately 200 additional living donor kidney transplants could be performed yearly in the United States if only altruistically balanced living donor kidney exchanges are performed. These mathematical computations, although imprecise, serve to give a general estimate of the potential impact of living donor exchange programs. This impact will certainly be enhanced if they are performed for other reasons, such as positive cross-matches, and also if they are eventually performed for altruistically unbalanced exchanges. Physical removal of anti-A and anti-B antibodies with concomitant potent immunosuppression provides an alternative approach for circumventing ABO incompatibilities; however, experience with these approaches consists only of small single-center studies (5-7). We believe that widespread application of these techniques should be advocated only after substantial multicenter trials have documented the success of these approaches. The successful experience of living unrelated donation is so compelling that it demands that the transplant community maximize opportunities for a patient to receive a living donor kidney. Although we realize that living donor kidney exchange programs do not fully address the organ donor shortage, we believe that they should be viewed as an important, worthwhile part of helping those patients who are otherwise unable to receive a living donor kidney. E.