Kidney Paired Donation Program Research Articles

A Branch-and-Price Algorithm Enhanced by Decision Diagrams for the Kidney Exchange Problem

Problem definition: Kidney paired donation programs allow patients registered with an incompatible donor to receive a suitable kidney from another donor, as long as the latter’s co-registered patient, if any, also receives a kidney from a different donor. The kidney exchange problem (KEP) aims to find an optimal collection of kidney exchanges taking the form of cycles and chains. Methodology/results: We develop the first decomposition method that is able to consider long cycles and long chains for projected large realistic instances. Particularly, we propose a branch-and-price framework in which the pricing problems are solved (for the first time in packing problems in a digraph) through multivalued decision diagrams. We present a new upper bound on the optimal value of the KEP, obtained via our master problem. Computational experiments show superior performance of our method over the state of the art by optimally solving almost all instances in the PrefLib library for multiple cycle and chain lengths. Managerial implications: Our algorithm also allows the prioritization of the solution composition, for example, chains over cycles or vice versa, and we conclude, similar to previous findings, that chains benefit the overall matching efficiency and highly sensitized patients. Funding: This work was supported by NSERC Discovery Grant (RGPIN-2021-02609). Supplemental Material: The e-companion is available at https://doi.org/10.1287/msom.2022.0192 .

Kidney paired donation in developing countries: A global perspective.

We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

The Questionable Burden of AB0 Incompatible Kidney Transplantation

Abstract Background AB0 incompatible kidney transplantation has become a genuine treatment for end-stage renal disease. Non-inferiority in long term graft function compared to AB0 compatible transplantation has been shown. However, the assumed burden due to complications owing to increased immunosuppression inherent to AB0 incompatible transplantation has not yet been quantified. Aims The aim of the study was to determine if AB0 incompatible recipients have additional morbidity and whether this burden is justified or whether kidney paired donation programs should be advocated. Methods From January 2000 to March 2020 46 AB0 incompatible living kidney transplantations were performed. Patients were matched with AB0 compatible recipients according to sex, age, underlying disease, year of transplantation, and duration of dialysis. Number and duration of readmissions, surgical complication rates according to Clavien-Dindo and its comprehensive complication index (CCI), kidney function, occurrence of new onset diabetes, as well as tumor incidence were analyzed. Results Readmission rate was not higher in AB0 incompatible recipients. The median difference in length of hospital stay for readmissions, CCI during primary hospital stay, and CCI for readmissions at 3, 6, 12 and >12 months after transplantation were comparable. Incidence of tumor and new onset diabetes after transplantation was not increased in incompatible recipients. Conclusions AB0 incompatible recipients do not suffer from a higher burden compared to AB0 compatible recipients. We currently recommend not delaying transplantation in AB0 incompatible pairs.

Many a Slip Twixt the Intake Form and the Living Donation.

Many a Slip Twixt the Intake Form and the Living Donation.

Long-Term Outcomes of Kidney Paired Donation Transplantation: A Single Center Retrospective Cohort Study

This study aimed to compare the kidney paired donation (KPD) program recipients with the traditional living donor kidney transplantation (LDKT) recipients regarding patient and graft survival. We retrospectively analyzed 141 recipients of the KPD program and 141 classic LDKT recipients that we matched for age and sex as controls between July 2005 and June 2019. We compared the 2 transplant groups for patient and kidney survival using the Kaplan-Maier test. We also performed Cox Regression analysis to examine factors affecting patient survival, including transplant type. The average follow-up period was 96.17 ± 44.22 months. Of the 282 patients, 88 died in the follow-up period. There was no statistically significant difference in graft and patient survival between the KPD and LDKT groups. In the Cox regression model, including the transplant type, only the serum creatinine level measured in the first month after discharge was a significant factor in predicting patient survival. The findings of this study indicate that the KPD program is an effective and reliable method to increase LDKT. Country-wide multicentric studies should confirm the results of this study. In countries where cadaver transplantation is insufficient, efforts should be made to expand the KPD program.

Donación renal pareada: beneficio de este programa en la tasa de trasplantes y sobrevida del injerto.

To demonstrate the experience since the transplant program under paired kidney donation implementation; program that increases the donation rate by 25-30% in hospitals with no inferior graft survival compared to directed living donor kidney transplantation. Observational, analytical, longitudinal and prospective study from December 2018 to July 2021. All G5 KDIGO chronic kidney patients who were HLA or ABO incompatible with their original donors in the pretransplant protocol and who were transplanted under the paired kidney donation program, were included. 22 kidney transplants were performed under this program. Survival of the graft and the patient 1 year after transplantation was 100%. The post-transplant glomerular filtration rate was 72.5 ± 17 ml/min/1.73 m2 body surface. 36.3% of hypersensitized patients were successfully transplanted. The in-hospital donation rate increased by 33.33%. Transplantation under the kidney paired donation program constitutes a real modality of successful transplantation when there is incompatibility with the original donor. The greater use and socialization of this program can increase the country kidney transplantation rate, reducing the waiting list. Our hospital represents the largest experience published in Mexico with this transplant program.

The living kidney donor profile index fails to discriminate allograft survival: implications for its use in kidney paired donation programs.

The inclusion of blood group- and human leukocyte antigen-compatible donor and recipient pairs (CPs) in kidney paired donation (KPD) programs is a novel strategy to increase living donor (LD) transplantation. Transplantation from a donor with a better Living Donor Kidney Profile Index (LKDPI) may encourage CP participation in KPD programs. We undertook parallel analyses using data from the Scientific Registry of Transplant Recipients and the Australia and New Zealand Dialysis and Transplant Registry to determine whether the LKDPI discriminates death-censored graft survival (DCGS) between LDs. Discrimination was assessed by the following: (1) the change in the Harrell C statistic with the sequential addition of variables in the LKDPI equation to reference models that included only recipient factors and (2) whether the LKDPI discriminated DCGS among pairs of prognosis-matched LD recipients. The addition of the LKDPI to reference models based on recipient variables increased the C statistic by only 0.02. Among prognosis-matched pairs, the C statistic in Cox models to determine the association of the LKDPI with DCGS was no better than chance alone (0.51 in the Scientific Registry of Transplant Recipient and 0.54 in the Australia and New Zealand Dialysis and Transplant Registry cohorts). We conclude that the LKDPI does not discriminate DCGS and should not be used to promote CP participation in KPD programs.

423.4: Raising the Potential of Transplantation With a KPD Collaborative Program

Purpose: Up to 30% of potential living donor/recipient pairs cannot proceed to live donor kidney transplantation (LDKT) for immunological reasons (ABO incompatibility or positive crossmatch). Kidney Paired Donation (KPD) programs have been conducted in various countries for over 20 years as an alternative for these patients. Our goal was to estimate the potential of paired transplantation when increasing the pool of pairs by collaboration between 2 centers in Brazil. Methods: We conducted simulated match-runs involving 2 centers: Santa Casa de Misericórdia de Juiz de Fora (SC) and Hospital das Clínicas da Universidade de São Paulo (HC). At SC, all the contraindicated donor-recipient pairs because of a positive crossmatch between January 2013 - February 2022 and whose recipients are still on the waitlist were included (N= 28 recipients and 39 donors). At HC, the pool is composed of pairs enrolled in a KPD study protocol that already performed its first paired transplant in March 2020 (N= 25 recipients and 28 donors). We used the StanfordKPD platform to optimize transplant numbers favoring high PRA recipients matches. Four acceptable ranges of DSAs MFI were established (<500, <1500, <3000 and <5000), three types of programs (accepting only 2-way exchanges; 2-and-3-way exchanges and N-way exchanges) and we also evaluated the possibility of collaboration between centers. Results: The demographic data of both pools are shown in Table 1. The results of various KPD match-runs are shown in Table 2. As was expected, the number of transplants increases when allowing longer chains, higher MFI thresholds and collaboration between the centers. Despite the high median PRA in the pool, the StanfordKPD platform was able to find a match for up to 64% of the recipients when allowing MFI <5000. This is especially possible when we combine KPD with desensitization.Conclusions: A KPD program can enable kidney transplant for hard-to-match patients, that tend to accumulate on the waitlist. The probability of finding a match rises with the increase of the pool of pairs and the flexibilization of the acceptance criteria.

316.10: Kidney Paired Donation in Latin America, From Theory To Practice

Introduction: Between 25-30% of couples will be ABO or HLA incompatible once they finish the transplant protocol. The Kidney Paired Donation (KPD) program is a modality that resolves this incompatibility by allowing donors to be exchanged. Acord to Newsletter transplant 2020, kidney transplant activity in Latin America under the KPD program is null, however there is a Guatemala case report in 2018 where they started this program and another report from 1998 in Mexico with a series of 12 transplant cases renal with exchange of donors. There has been an evolution over time of the KPD at an international level and to date computer algorithms are used based on the blood group of the donor-recipient, sensitization status and the size of the pool of incompatible couples, determining the best probability of matching success within of the program by optimizing the successful matching of donors and recipients according to the principles of fairness, utility and justice. Method: Observational, analytical, longitudinal and prospective study from December 2018 to July 2021. Were included all G5 KDIGO chronic kidney patients who were HLA or ABO incompatible with their original donors in the pretransplant protocol and who were transplanted under the program of paired kidney donation in the Central Military Hospital, Mexico, City. Results: 22 kidney transplants were performed under this program. The most common CKD etiology was not determined (ND) with 31.8%. Survival of the graft and the patient 1 year after transplantation was 100%. The post-transplant glomerular filtration rate receptor (GFR) was 72.5 (± 17) ml/min/1.73 m2SC; the GFR post-donación was 75.04 (± 15.98) ml/min/1.73/m2SC. 36.3% of hypersensitized patients were successfully transplanted whitout plasmapheresis. The mean age of the recipients was 35.67 (± 12.45) years. The waiting time from admission to the paired program to the transplant was 4.9 months.Inter-hospital donor exchanges have already been carried out; the in-hospital donation rate increased by 33.33%. Discussion: The Case reports or case series published in latinoamerica´s countries show an adequate evolution of the patients and grafts without major complications as our Hospital. Conclusion: Transplantation under the paired kidney donation program constitutes a real modality of successful transplantation when there is incompatibility with the original donor. Increased utilization and socialization of this program can increase the country kidney transplantation rate, reducing the waiting list. Our hospital represents the largest published experience in Mexico and latinamerica with this transplant program.

A theoretical and computational equilibria analysis of a multi-player kidney exchange program

A main aim of kidney exchange programs (KEPs) is to maximize the number of transplants within a pool of incompatible patient-donor pairs by exchanging donors. A KEP involving pairs from pools of several hospitals, regions, or countries has the potential to increase the number of transplants. These entities may behave strategically and strive to maximize the transplant benefit for their patients. Recently, a decentralized non-cooperative game was formulated to model this situation, and the game solutions (equilibria) for the 2-player case were characterized when each player’s utility is the number of her patients receiving a kidney and exchanges are restricted to pairwise. In this paper, we generalize the result on the existence of social welfare equilibra for N-players and discuss the impact in the game solutions when transplant information quality is introduced, changing the players’ utilities. Furthermore, the game theory model is analyzed through computational experiments on instances generated by leveraging data of the Canadian Kidney Paired Donation Program. These experiments highlight the importance of using the concept of Nash equilibrium, as well as, the need of further research to assist policy makers once measures on transplant quality are available.

Living donor kidney paired exchange: An observational study

BackgroundKidney transplantation is the treatment of choice for patients with end-stage renal disease (ESKD). Kidney paired donation (KPD) provides the chance to match an incompatible donor/recipient pair with another donor and recipient in a similar condition. We aimed to compare the outcomes of pair exchange kidney transplantation with traditional live donor kidney transplantation in our context. MethodA review of medical records of 62 patients (31 pairs) who underwent two-way conventional living kidney pair exchange from July 2016 to June 2021 was done. The control group was considered those 62 patients who had undergone classic live donor kidney transplantation (LDKT) during the study period. The patient's demographics, intraoperative and postoperative variables including delayed graft function, length of hospital stay, graft survival, patient survival, and rejections rates were compared between the groups (KPD and LDKT). ResultsThe majority of recipients were male (77.4 and 80.6%) while donors were female (77.4 and 69.4%) in KPD and the LDKT groups. Mean ages were 37 years (range: 19–59) and 37 years (range: 17–65) for the recipient's in KPD and the LDKT. KPD transplantation was performed in 62 recipients to avoid blood group incompatibility. There were no significant differences in outcomes comprising delayed graft function (1.6 and 3.2%), graft survival (100% in both groups), patient survival (95.2 and 96.8%), and rejections rates (1.6 and 1.6%) between KPD and LDKT group (P > 0.005). The length of stay was similar (5.9 and 5.7 days) in KPD and LDKT groups (P > 0.005). ConclusionsThe outcomes of KPD were comparable with classic LDKT in terms of delayed graft function, length of hospital stay, graft survival, patient survival, and rejections rates in our study. Therefore, the kidney paired donation program should be encouraged and promoted in centers where the ABO-incompatible transplant is expensive with added risk and the rate of deceased donor transplantation is very low.

Increasing transplantability in Brazil: time to discuss Kidney Paired Donation.

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 Psychosocial Adjustment of Kidney Recipients in Canada's Kidney Paired Donation Program.

Introduction: Kidney paired donation programs have been implemented globally. The involvement of at least 2 donors in these programs might exacerbate recipients’ debt of gratitude and guilt, worries about the donor's health, and worries about graft failure documented by previous studies. However, there is an absence of research on the psychosocial implications of kidney paired donation. This study aimed to provide an in-depth examination of recipients’ experience of kidney paired donation, with a focus on psychosocial adjustment. Methods/Approach: Individual interviews were conducted with 8 recipients who received a transplant through Canada's Kidney Paired Donation program. Data was analyzed using Interpretative Phenomenological Analysis. Findings: Four themes emerged: (a) an emotionally charged relationship with the known donor, (b) optimal distance regulation in the relationship with the anonymous donor, (c) kidney paired donation as a series of ups and downs, and (d) multilayered gratitude. Discussion: Findings are considered in relation to extant literature. Issues relevant to the transplant community's clinical and research efforts to provide kidney recipients responsive care are discussed.

Kidney paired donation in Brazil - it is time to talk about it.

We appreciate the opportunity to have this scientific discussion regarding how Kidney Paired Donation (KPD) could increase transplantability in Brazil. As organ donation rates remain unable to meet the needs of individuals waiting for transplants, especially for highly sensitized recipients1 , it is necessary to develop solutions to address it. We understand that KPD programs have been implemented worldwide to reduce organ demand and supply gap, especially vulnerable recipients.

Current Approaches to Desensitization in Solid Organ Transplantation.

Major advancements in the development of HLA antibody detection techniques and our understanding of the outcomes of solid organ transplant in the context of HLA antibody have occurred since the relevance of sensitization was first recognized nearly 50 years ago. Additionally, kidney paired donation programs (KPD) have become widespread, deceased donor allocation policies have changed, and several new therapeutic options have become available with promise to reduce HLA antibody. In this overview we aim to provide thoughtful guidance about when desensitization in kidney transplantation should be considered taking into account the outcomes of HLA incompatible transplantation. Novel therapeutics, desensitization endpoints, and strategies for future study will also be discussed. While most of our understanding about desensitization comes from studying kidney transplant candidates and recipients, many of the concepts discussed can be easily applied to desensitization in all of solid organ transplantation.

Compatible Donor and Recipient Pairs' Perspectives on Participation in Kidney Paired Donation Programs: A Mixed-Methods Study.

Background:Compatible pair participation in kidney paired donation (KPD) may increase the likelihood of finding suitable matches for all registered pairs. Retrospective studies have shown variable enthusiasm for participating in KPD in compatible pairs.Objective:The study objective was to gather potential living donor (PLD) and transplant candidate (TC) perspectives on compatible pair participation in KPD.Design:Surveys and qualitative interviews.Setting:Three transplant programs in Canada: Centre hospitalier de l’Université de Montréal in Montreal (Québec), Vancouver General Hospital, and St. Paul’s Hospital in Vancouver (British Columbia).Patients:Both PLDs and TCs undergoing evaluation for donation/transplantation between 2016 and 2018 at 3 transplant programs in Canada.Methods:Descriptive statistical analysis was performed for the results of the survey and thematic and content analysis method was used for the content of the qualitative interviews.Results:A total of 116 PLDs and 111 TCs completed surveys and an additional 18 PLDs and 17 TCs underwent semi-directed interviews. Of those surveyed, 61.2% of PLDs and 76.6% of TCs reported a willingness to participate in KPD as a compatible pair. The possibility of a more optimally matched kidney for the TC and policies ensuring prioritization of the TC for repeat transplantation in the event of early graft failure increased willingness to participate in KPD. Major concerns expressed during the interviews included the desire to retain the emotional bond of directed donation, the fear of chain breaks or donor reneging, delays in transplantation, and additional travel associated with participation in KPD.Limitation:The limitations of this study are that it was conducted in only 3 Canadian transplant programs and that the interviews and surveys were in French and in English. As a consequence, the results may not be reflective of the views of individuals not living in these 2 provinces and from ethnic minority populations.Conclusion:Most of the compatible PLDs and TCs surveyed were willing to participate in KPD. Ensuring timely transplantation and a more optimal match for TCs and offering a policy of reciprocity to ensure timely repeat transplantation for compatible recipients if their allograft fails post KPD transplant may further increase compatible pair participation in KPD.

The impact of COVID-19 on the Canadian Kidney Paired Donation program: an opportunity for universal implementation of kidney shipping

"Never let a good crisis go to waste." - Sir Winston Churchill.

Is it the time to apply the model of Czech-Austrian kidney paired donation program?

Living donor (LD) kidney transplantation is currently the best treatment of choice for patients with end stage renal disease. However, in a significant amount of cases there are immunological barriers between the potential donor and recipient. While kidney paired donation (KPD) or kidney exchange program (KEP) would certainly help to overcome these barriers and find immunological appropriate donor for each recipient, a single institutional or even a small country national list can be unsuccessful as numbers really do matter in this situation.

Crossing borders to facilitate live donor kidney transplantation: the Czech-Austrian kidney paired donation program - a retrospective study.

Kidney paired donation (KPD) is a valuable tool to overcome immunological barriers in living donor transplantation. While small national registries encounter difficulties in finding compatible matches, multi-national KPD may be a useful strategy to facilitate transplantation. The Czech (Prague) and Austrian (Vienna) KPD programs, both initiated in 2011, were merged in 2015. A bi-national algorithm allowed for ABO- and low-level HLA antibody-incompatible exchanges, including the option of altruistic donor-initiated domino chains. Between 2011 and 2019, 222 recipients and their incompatible donors were registered. Of those, 95.7% (Prague) and 67.9% (Vienna) entered into KPD registries, and 81 patients received a transplant (95% 3-year graft survival). Inclusion of ABO-incompatible pairs in the Czech program contributed to higher KPD transplant rates (42.6% vs. 23.6% in Austria). After 2015 (11 bi-national match runs), the median pool size increased to 18 pairs, yielding 33 transplants (8 via cross-border exchanges). While matching rates doubled in Austria (from 9.1% to 18.8%), rates decreased in the Czech program, partly due to implementation of more stringent HLA antibody thresholds. Our results demonstrate the feasibility of merging small national KPD programs to increase pool sizes and may encourage the implementation of multi-national registries to expand the full potential of KPD.

Ten Years of Kidney Paired Donation at Mayo Clinic: The Benefits of Incorporating ABO/HLA Compatible Pairs.

We examined the 10-year experience of Mayo Clinic's kidney paired donation (KPD).We aimed to determine the benefits for the recipients of enrolled ABO/HLA compatible pairs and determine the factors associated with prolonged KPD waiting time. We performed a retrospective study of 332 kidney transplants facilitated by the Mayo 3-site KPD program from September 2007 to June 2018. The median (interquartile range) time from KPD entry to transplantation was 89 days (42-187 days). The factors independently associated with receiving a transplant >3 months after KPD entry included recipient blood type O and calculated panel reactive antibodies ≥98%. Fifty-four ABO/HLA compatible pairs participated in KPD for the following reasons: cytomegalovirus mismatch (18.5% [10/54]), Epstein-Barr virus (EBV) mismatch (EBV) (9.3% [5/54]), age/size mismatch (51.9% [28/54]), or altruistic reasons (20.3% [11/54]). Cytomegalovirus and EBV mismatch were avoided in 90% (9/10) and 100% (5/5) of cases. Recipients who entered KPD for age/size mismatch and altruistic reasons received kidneys from donors with lower Living Kidney Donor Profile Index scores than their actual donor (median [interquartile range] 31.5 [12.3-47]; P < 0.001 and 26 (-1 to 46); P = 0.01 points lower, respectively). Median time to transplant from KPD entry for compatible pair recipients was 70 days (41-163 days), and 44.4% (24/54) of these transplants were preemptive. All chains/swaps incorporating compatible pairs included ABO/HLA incompatible pairs. KPD should be considered for all living donor/recipient pairs because the recipients of these pairs can derive personal benefit from KPD while increasing the donor pool for difficult to match pairs.