Allocation and matching in kidney exchange programs

Optimal integration of desensitization protocols into kidney paired donation (KPD) programs

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. While living donors provide anywhere from a small to a large fraction of kidneys for transplantation in different countries, at least one-third of these donors are incompatible with their potential recipients. To overcome these challenges, kidney paired donation (KPD) programs have been established that organize donor exchanges to find matches among the pool of incompatible pairs. Each program has developed its own features to accommodate local needs. Reasons for participating in KPD include blood group incompatibility, sensitization of the recipient against the donor, and the potential for improvement in transplant quality (e.g., age difference or graft size), and tissue compatibility. KPD programs use sophisticated algorithms to find matches among the pool of donor-recipient pairs to create simultaneous 2-way, 3-way, or 4-way exchanges or more complex non-simultaneous chains of transplants. These KPD allocation systems should be medically sound and ethically acceptable according to the principles of equity, utility, and justice. The variety of possible exchanges provided by these algorithms allows for maximizing the number of transplants, increasing the quality of transplants, and accommodating patients who are difficult to match. In this review, we describe several examples of successful KPD programs with diverse organizational approaches. By highlighting the strategies used by these programs to meet the needs of their patient populations, we aim to inspire improvements in existing programs and to provide a framework for expanding KPD to better serve international transplant communities.

Introduction:Kidney transplantation (KT) is the best treatment for chronic kidney disease. In Brazil, there are currently more than 26 thousand patients on the waitlist. Kidney Paired Donation (KPD) offers an incompatible donor-recipient pair the possibility to exchange with another pair in the same situation, it is a strategy to raise the number of KT.Discussion:KPD ceased being merely an idea over 20 years ago. It currently accounts for 16.2% of living donors KT (LDKT) in the USA and 8% in Europe. The results are similar to other LDKT. It is a promising alternative especially for highly sensitized recipients, who tend to accumulate on the waitlist. KPD is not limited to developed countries, as excellent results were already published in India in 2014. In Guatemala, the first LDKT through KPD was performed in 2011. However, the practice remains limited to isolated cases in Latin America.Conclusion:KPD programs with different dimensions, acceptance rules and allocation criteria are being developed and expanded worldwide to meet the demands of patients. The rise in transplantability brought about by KPD mostly meets the needs of highly sensitized patients. The Brazilian transplant program is mature enough to accept the challenge of starting its KPD program, intended primarily to benefit patients who have a low probability of receiving a transplant from a deceased donor.

The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned. In the sense of acritical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants. Aretrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed. Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and areduced longevity of the grafts. Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs.

First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States. To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors. Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk. Kidney paired donation and live donor renal transplantation. Patient survival, graft survival, serum creatinine levels, rejection episodes. A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%). This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.

Kidney exchange programs (KEPs) allow the exchange of kidneys between incompatible donor-recipient pairs. Optimization approaches can help KEPs in defining which transplants should be made among all incompatible pairs according to some objective. The most common objective is to maximize the number of transplants. In this paper, we propose an integer programming model which addresses the objective of maximizing the expected number of transplants, given that there are equal probabilities of failure associated with vertices and arcs. The model is compact, i.e. has a polynomial number of decision variables and constraints, and therefore can be solved directly by a general purpose integer programming solver (e.g. Cplex).

ObjectivesLiving donor kidney transplantation (LTx) is the preferred treatment for patients with end-stage renal disease. Kidney exchange programs (KEPs) promote LTx by facilitating exchange of donors among patients who are not compatible with their donors. We analyze and maximize the efficacy and effectiveness of KEPS from a health value perspective and the health value of altruistic donation in KEPs. MethodsWe developed a Markov model for the health outcomes of patients, which was embedded in a discrete event simulation model to assess the effectiveness of allocation policies in KEPs. A new allocation policy to maximize health value was developed on the basis of integer programing techniques. The evidence-based transition probabilities in the Markov model were based on data from the Dutch KEP using a variety of econometric models. Scenarios analysis was presented to improve robustness. ResultsThe efficacy of the Dutch KEP without altruistic donation is reflected by the increase in expected discounted quality-adjusted life-years (QALYs) by 3.23 from 6.42 to 9.65. The present Dutch policy and the policy to maximize the number of transplants achieve 63% of the potential efficacy gain (2.11 discounted QALYs). The new policy achieves 69% of this gain (2.33 discounted QALYs). When systematically enrolling altruistic donors in the KEP, the new policy increased expected discounted QALYs by 4.05 to 10.27 and reduced inequities for patients with blood type O. ConclusionsThe Dutch KEP can increase health value for patients by more than half. An allocation policy that maximizes health outcomes and maximally allows altruistic donation can yield significant further improvements.

Case report of swap kidney transplantation in Chhattisgarh – Challenges and solution

Kidney paired donation (KPD) is increasing the number of living donor transplants. Two major obstacles prevent moving KPD forward in the United States: (1) achieving a critical mass of pairs to efficiently find matches and (2) efficiently coordinating KPD transplants between multiple transplant centers. Two large regional programs, The New England Program for Kidney Exchange (NEPKE) and the Mid-Atlantic Paired Exchange Program (MAPEP) have developed a system of protocols to effectively increase the number of KPD transplants. Incompatible pairs and nondirected donors (NDD) are referred to the system through transplant centers. Donor and recipient ABO, human leukocyte antigen, and recipient human leukocyte antigen antibody screening are used to determine potential matches. Utilization of a computer optimization algorithm matches pairs in two- and three-way exchanges, NDD chains, and list exchange chains. Team conference calls regarding transfer of information, crossmatches, surgery date, coordination of simultaneous donor nephrectomies, and other issues are coordinated as needed. Ten matches moved forward to donation and transplantation, and one is pending. Eight of these matches involved NDD chains, two 2-way exchanges, and 1 a list exchange chain. These matches resulted in 27 transplants. Eighteen transplants occurred in NEPKE-only transplant centers, four in MAPEP-only centers, and an additional five were crossregional. The collaboration of NEPKE and MAPEP has demonstrated that crossregional coordination is feasible and expands the number of transplants performed beyond the capability of either program alone, especially when combined with computer optimization and multiple-type matches of three-way, NDD chains, and list exchange chains.

Chapter 25 - Renal Transplantation Across HLA and ABO Barriers

Increasing living-donor kidney transplant procedures via kidney paired donations could help combat organ shortages. We examined whether a higher volume of kidney paired donation transplants would lead to increased center performance. Kidney paired donation, living-donor, and deceased-donor transplant data from 165 centers between 2012 and 2016 were obtained from the UNOS OPTN database. The fixed-effects model was used for panel analysis based on Durbin-Wu-Hausman tests (P < .001). Regression analyses tested associations between total transplant number and kidney paired donation-to-living donor kidney transplant ratio, incorporating up to 2-year lag terms. Regression analyses also tested associations between number of new wait list registrations and kidney paired donation transplant ratio. Mean and median number of kidney paired donor transplants equaled 3.59 and 1.2, respectively. Only 5 centers performed > 20 paired donation transplants annually. Mean and median ratios of paired donation transplants were 0.54 and 0.11. Total transplant number was not associated with paired donation transplant ratio of the same year (b= -.425, P = .662) or with that of 2 prior years (P = .830 and P = .629, respectively). Similarly, new wait list registrations were not correlated with paired donation transplant ratio of the same year (P= .501, P = .851) or that of 2 prior years (P = .792 and P = .816, respectively). When transplant centers were divided into those performing ≥ 10 paired donation trans-plants annually (18 transplant center, n = 90) versus those performing < 10 annually (147 transplant center, n = 735), no significant effects were shown (P > .10). Kidney paired donation transplant does not appear to affect transplant center performance. This may be due to the small volume of these transplants currently performed by centers, thereby limiting overall growth in the number of transplants and new registrations.

Background and Aims Living donor kidney transplantation (LDKT) is the best option for renal replacement therapy, as it offers better outcomes and quality of life for patients. Traditionally, transplants have been performed between donors and recipients with compatible blood type. However, in recent years, ABO-incompatible transplants have emerged as an effective alternative for patients on the waiting list without a compatible donor. Method A single-center retrospective study was conducted, including ABO-incompatible LDKT patients in our hospital between 2013 and 2023, with a minimum follow-up of 1 year. Desensitization protocol with anti-CD20 monoclonal antibodies, specific immunoadsorption (IA), and polyclonal immunoglobulins was implemented. Induction immunosuppression consisted of thymoglobulin, prednisone, tacrolimus, and mycophenolic acid. Results Twenty-four patients were included. The average age of donors and recipients was 55 ± 8 and 54 ± 9 years, respectively, with a majority of female donors (80%) and male recipients (60%). Marriages represented the most common relationship (68%). The mean follow-up time was 42 months. 80% of patients required pre-transplant IA (average of 4 sessions), while 41% required post-transplant IA (average 3.5 sessions). All patients had pre-transplant isoagglutinin (ISO) titers &amp;lt;1/8, and post-transplant ISO titers remained low in most cases. 16% of patients experienced acute rejection (cellular and/or humoral). One patient developed graft thrombosis 15 days post-transplant due to humoral rejection mediated by ISO. Graft survival was 96% in the first year and remained stable throughout the follow-up, with mean serum creatinine levels of 129 ± 46 µmol/L and no proteinuria. Patient survival was 94%. No higher rates of infections or neoplasms were observed. Conclusion Despite the immunological challenges inherent in ABO-incompatible LDKT, current desensitization protocols allow for acceptable rates of acute rejection and provide satisfactory long-term graft and patient survival.

Renal patients who have a willing but incompatible donor can decide to participate in a kidney exchange program (KEP). The goal of a KEP is to identify sets of incompatible pairs that can exchange donors, leading to compatible transplants for each recipient. Significant uncertainty is involved in this process, as planned transplants may be canceled for many reasons. It is therefore crucial to take into account failures while planning exchanges. In this paper, we consider a robust variant of this problem with recourse studied in the literature that takes into account failures of donors or recipients. This problem belongs to the class of defender–attacker–defender (DAD) models. We propose a cutting plane method for solving the attacker–defender subproblem based on two commonly used mixed-integer programming formulations for kidney exchange problems. Our results imply a running time improvement of one order of magnitude compared to the state-of-the-art. Moreover, our cutting plane methods can solve many previously unsolved instances. Furthermore, we propose a new practical policy for recourse in KEPs and show that the robust optimization problem concerning this policy is tractable for small to mid-size KEPs in practice.

Specific issues in living donor kidney transplantation: ABO – incompatibility

In 2001 a protocol for ABO-incompatible (ABOi) kidney transplantation based on antigen-specific immunoadsorption and rituximab was introduced at our center, short-term results being comparable with those of ABO-compatible (ABOc) living donor kidney transplantation. Of greater importance, however, is long-term graft function, thus far not evaluated. The aim of this study was therefore to assess long-term results of this protocol. Twenty ABOi kidney recipients with more than 12-month follow-up were included in the study: all adult crossmatch negative ABOi kidney recipients (n=15) were compared with an adult ABOc living donor recipient control group (n=30), and all pediatric ABOi kidney recipients (<16 years of age) (n=5) were compared with a group of pediatric ABOc kidney recipients (n=18). Mean follow-up was three years. There was no significant difference in patient survival, nor in graft survival or in the incidence of acute rejection in any of the groups. In the adult kidney recipients mean glomerular filtration rate was equivalent at all time points (79-83 mL/min), as was Deltas-creatinine. In the pediatric groups, Deltas-creatinine was similar but glomerular filtration rate lower among the ABOi kidney recipients. There was a significant reduction (P<0.0001) without rebound in A/B antibody titers after transplantation (median IgG 1:2 and median IgM 1:1>1 year posttransplant) compared with pretransplant levels (median IgG 1:32 and IgM 1:16). We conclude that ABOi kidney transplantation using antigen-specific immunoadsorption and rituximab is equivalent to ABOc living donor kidney transplantation. ABOi transplantation after this protocol does not have a negative impact on long-term graft function.