Comparison of Kidney Paired Donation Transplantations with Living Related Donor Kidney Transplantation: Implications for National Kidney Paired Donation Program

Background: Kidney Paired Donation (KPD) is a rapidly growing modality for facilitating living related donor kidney transplantation (LRDKTx) for patients who are incompatible with their healthy, willing, and living donors. Data scarcity on the outcome of KPD versus LRDKTx prompted us to review our experience. Materials and methods: This was a single-center study of 224 patients on regular follow-up, who underwent LRDRTx from January 2010 to June 2012 at our institute. The aim of this study was to compare short-term graft survival, patient survival and rejection rates of KPD (group 1, n = 34) with those of LRDKTx (group 2, n = 190). All the recipients received triple immunosuppression and thymoglobulin induction in KPD group. Kaplan–Meier curves were used for survival analysis. In group 1, mean recipient age was 35.5 ± 13.2 years, 29 were men and mean donor age was 44.4 ± 8.17 years, 10 were men. In group 2, mean recipient age was 29.1 ± 10 years, 155 were men and mean donor age was 47.5 ± 9.69 years, 74 were men. Mean human leukocyte antigen (HLA) matching in group 1 and 2 was 1 versus 3.2 (p < 0.05). Results: One- and two-year patient survival showed no significant difference between the two groups (97.1%, 97.1% vs. 96.2%, 94.8%, respectively, p = 0.81). Death-censored graft survival also showed no significant difference between the two groups (97.1%, 97.1%, vs. 97.6%, 97.6%, p = 0.73). Acute rejection incidence was also similar (8.7% vs. 9.9%, p > 0.62). Conclusions: Our study showed similar graft survival, patient survival and rejection rates of KPD versus LRDKTx over 2 years post-transplantation, encouraging the use of this approach for national KPD program.     

Twenty-Two Nondirected Kidney Donors: An Update on a Single Center''s Experience

At the University of Minnesota, we have defined 'nondirected donation' as organ donation by a volunteer who offered to donate an organ to anyone on the cadaver waiting list. From October 1, 1997, through October 31, 2003, we have had 360 inquiries about nondirected donation, have completed 42 detailed nondirected donor (NDD) evaluations for kidney donation, and have performed 22 NDD transplants. We herein review our program policies and how they have evolved, describe our evaluation and the motivation of our potential donors, summarize the outcome of NDD transplants, and raise issues requiring further attention and study. Our experience continues to support nondirected donation for kidney transplants.     

Successful Three‐Way Kidney Paired Donation with Cross‐Country Live Donor Allograft Transport

Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000—2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard‐to‐match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well‐matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.     

The Roles of Dominos and Nonsimultaneous Chains in Kidney Paired Donation

Efforts to expand kidney paired donation have included matching nondirected donors (NDDs) to incompatible pairs. In domino paired donation (DPD), an NDD gives to the recipient of an incompatible pair, beginning a string of simultaneous transplants that ends with a living donor giving to a recipient on the deceased donor waitlist. Recently, nonsimultaneous extended altruistic donor (NEAD) chains were introduced. In a NEAD chain, the last donor of the string of transplants initiated by an NDD is reserved to donate at a later time. Our aim was to project the impact of each of these strategies over 2 years of operation for paired donation programs that also allocate a given number of NDDs. Each NDD facilitated an average of 1.99 transplants using DPD versus 1.90 transplants using NEAD chains (p = 0.3), or 1.0 transplants donating directly to the waitlist (p < 0.001). NEAD chains did not yield more transplants compared with simultaneous DPD. Both DPD and NEAD chains relax reciprocality requirements and rebalance the blood-type distribution of donors. Because traditional paired donation will leave many incompatible pairs unmatched, novel approaches like DPD and NEAD chains must be explored if paired donation programs are to help a greater number of people.     

Dynamic Challenges Inhibiting Optimal Adoption of Kidney Paired Donation: Findings of a Consensus Conference

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29–30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.     

The Incorporation of an Advanced Donation Program Into Kidney Paired Exchange: Initial Experience of the National Kidney Registry

The continued growth of kidney paired donation (KPD) to facilitate transplantation for otherwise incompatible or suboptimal living kidney donors and recipients has depended on a balance between the logistics required for patients and the collaborating transplant centers. The formation of chains for KPD and the shipping of kidneys have permitted networks such as the National Kidney Registry (NKR) to offer KPD to patients over a transcontinental area. However, over the last 3 years, we have encountered patient requests for a more flexible experience in KPD to meet their individual needs often due to rigid time constraints. To accommodate these requests, we have developed an Advanced Donation Program (ADP) in which the donor desires to donate by a specific date, but their paired recipient has not yet been matched to a specific donor or scheduled for surgery. After obtaining careful informed consent from both the donor and paired recipient, 10 KPD chains were constructed using an ADP donor. These 10 ADP donors have facilitated 47 transplants, and thus far eight of their paired recipients have received a kidney within a mean of 178 (range 10–562) days. The ADP is a viable method to support time limited donors in a KPD network.     

Utilizing List Exchange and Nondirected Donation through ''Chain'' Paired Kidney Donations

In a list exchange (LE), the intended recipient in an incompatible pair receives priority on the deceased donor waitlist (DD-waitlist) after the paired incompatible donor donates a kidney to a DD-waitlist candidate. A nondirected donor's (ND-D) kidney is usually transplanted directly to a DD-waitlist candidate. These two established practices would help even more transplant candidates if they were integrated with kidney paired donation (KPD). We consider a scenario in which the donor of an LE intended recipient (LE-IR) donates to a compatible KPD intended recipient (KPD-IR), and the KPD donor (KPD-D) donates to the waitlist (an LE-chain). We consider a similar scenario in which an ND-D donates to a KPD-IR and the KPD-D donates to the DD-waitlist (an ND-chain). Using data derived from the New England Program for Kidney Exchange (NEPKE) and from OPTN/SRTR recipient-donor distributions, simulations are presented to evaluate the potential impact of chain exchanges coordinated with KPD. LE donors (LE-D) and ND-D who are ABO-O result in the highest number of additional transplants, while results for ABO-A and B donors are similar to each other. We recommend that both LE and ND donations be utilized through chain exchanges.     

Planning for Uncertainty and Fallbacks Can Increase the Number of Transplants in a Kidney‐Paired Donation Program

A kidney‐paired donation (KPD) pool consists of transplant candidates and their incompatible donors, along with nondirected donors (NDDs). In a match run, exchanges are arranged among pairs in the pool via cycles, as well as chains created from NDDs. A problem of importance is how to arrange cycles and chains to optimize the number of transplants. We outline and examine, through example and by simulation, four schemes for selecting potential matches in a realistic model of a KPD system; proposed schemes take account of probabilities that chosen transplants may not be completed as well as allowing for contingency plans when the optimal solution fails. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Donation, the simulations extend over 8 match runs, with 30 pairs and 1 NDD added between each run. Schemes that incorporate uncertainties and fallbacks into the selection process yield substantially more transplants on average, increasing the number of transplants by as much as 40% compared to a standard selection scheme. The gain depends on the degree of uncertainty in the system. The proposed approaches can be easily implemented and provide substantial advantages over current KPD matching algorithms.     

Single‐Center Kidney Paired Donation: The Methodist San Antonio Experience

Many potential kidney transplant recipients are unable to receive a live donor transplant due to crossmatch or blood type incompatibility. Kidney paired donation increases access to live donor transplantation but has been significantly underutilized. We established a kidney paired donation program including consented incompatible donor/recipient pairs as well as compatible pairs with older non‐human leukocyte antigen identical donors. Over a 3‐year period, a total of 134 paired donor transplants were performed, including 117 incompatible pairs and 17 compatible pairs. All transplants were done with negative flow cytometry crossmatches and five were done with desensitization combined with paired donation. Kidney paired donation transplants included two‐way and three‐way exchanges as well as three chains initiated by nondirected donors. Of the sensitized recipients transplanted by paired donation, 44% had calculated panel reactive antibody levels greater than 80%. Transplantation of females and prior transplant recipients was significantly higher with paired donation. Only three episodes of rejection occurred and no transplants were lost due to rejection. These data highlight the potential of kidney paired donation and suggest that all transplant centers should be actively engaged in paired donation to increase access to live donor transplantation.     

Successful Expansion of the Living Donor Pool by Alternative Living Donation Programs

Between January 2000 and December 2007, 786 potential recipients and 1059 potential donors attended our pretransplant unit with the request for a living-donor renal transplant procedure. The recipients brought one potential donor in 77.2% and two or more donors in 22.8% of cases. In the regular living donor program, a compatible donor was found for 467 recipients. Without considering alternative donation, 579 donors would have been refused. Alternative living donation programs led to 114 compatible combinations: kidney-exchange program (35), ABO-incompatible donation (25), anonymous donation (37) and domino-paired anonymous donation (17). Together, the 114 alternative program donations and the 467 regular living donations led to 581 living donor transplantations (24.4% increase). Eventually for 54.9% (581/1059) of our donors, a compatible combination was found. Donor–recipient incompatibility comprised 19.4% (89/458) in the final refused population, which is 8.8% of the potential donor–recipient couples. Without considering alternative donation, 30.1% (174/579) of the refused donors would have been refused on incompatibility and 6.4% (37/579) because they were anonymous. This is 20% of the potential donor population (211/1059). The implementation of alternative living donation programs led to a significant increase in the number of transplantations, while transplantations via the direct donation program steadily increased.     

Optimizing Outcomes in Pediatric Renal Transplantation Through the Australian Paired Kidney Exchange Program

Kidney paired donation (KPD) programs offer the opportunity to enable living kidney donation when immunological and other barriers prevent safe directed donation. Children are likely to require multiple transplants during their lifetime; therefore, high‐level histocompatibility and organ quality matching are key priorities. Details are given for a cohort of seven pediatric renal transplantations performed through the Australian Kidney Exchange (AKX), including barriers to alternative transplantation and outcomes after KPD. Reasons for entering the KPD program were preformed donor‐specific antibodies to their registered donor in five cases, ABO mismatch, and avoidance of the risk of exposure to hepatitis B virus. Four recipients were highly sensitized. All patients received transplants with organs of lower immunological risk compared with their registered donors. HLA eplet mismatch scores were calculated for donor–recipient pairs; three patients had improved eplet mismatch load with AKX donor compared with their registered donor. All grafts are functioning, with a mean estimated glomerular filtration rate of 77 mL/min/1.73 m² (range 46–94 mL) and a follow‐up range of 8–54 months, and no patient experienced clinical or histological rejection. KPD is a viable strategy to overcome many barriers to living donation for pediatric patients who have an otherwise suitable donor and provides an opportunity to minimize immunological risks.     

Ethical Considerations for Participation of Nondirected Living Donors in Kidney Exchange Programs

Kidneys from nondirected donors (NDDs) have historically been allocated directly to the deceased donor wait list (DDWL). Recently, however, NDDs have participated in kidney exchange (KE) procedures, including KE ‘chains’, which have received considerable media attention. This increasing application of KE chains with NDD participation has occurred with limited ethical analysis and without ethical guidelines. This article aims to provide a rigorous ethical evaluation of NDDs and chain KEs. NDDs and bridge donors (BDs) (i.e. living donors who link KE procedures within KE chains) raise several ethical concerns including coercion, privacy, confidentiality, exploitation and commercialization. In addition, although NDD participation in KE procedures may increase transplant numbers, it may also reduce NDD kidney allocation to the DDWL, and disadvantage vulnerable populations, particularly O blood group candidates. Open KE chains (also termed ‘never‐ending’ chains) result in a permanent diversion of NDD kidneys from the DDWL. The concept of limited KE chains is discussed as an ethically preferable means for protecting NDDs and BDs from coercion and minimizing ‘backing out’, whereas ‘honor systems’ are rejected because they are coercive and override autonomy. Recent occurrences of BDs backing out argue for adoption of ethically based protective measures for NDD participation in KE.     

Long‐Term Non–End‐Stage Renal Disease Risks After Living Kidney Donation

Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non–end‐stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non‐ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less‐than‐ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.     

APOL1‐Associated End‐Stage Renal Disease in a Living Kidney Transplant Donor

Homozygosity for apolipoprotein‐L1 (APOL1) risk variants has emerged as an important predictor of renal disease in individuals of African descent over the past several years. Additionally, these risk variants may be important predictors of renal allograft failure when present in a living or deceased donor. Currently, there is no universal recommendation for screening of potential donors. We present a case of end‐stage renal disease with focal segmental glomerulosclerosis in a living donor 7 years following donor nephrectomy. Genetic assessment revealed homozygosity for the G1 high‐risk APOL1 variant.     

The 6‐year clinical outcomes for patients registered in a multiregional United States Kidney Paired Donation program ‐ a retrospective study

We examined what happened during a 6‐year period to 1121 end‐stage renal disease patients who registered with their willing/incompatible living donors for kidney exchanges with the Alliance for Paired Donation (APD). Of all patients, 65% were transplanted: 37% in kidney paired donation (APD‐KPD, APD‐other‐KPD); 10% with compatible live donors (APD‐LD); and 18% with deceased donors (APD‐DD). The remaining patients were withdrawn (sick/died/others; 15%), or were still waiting (20%). For those patients with a cPRA 0–94%, 72% received a transplant. In contrast, only 49% of very highly sensitized (VHS; cPRA 95–100%) were transplanted. Of the VHS patients, 50% were transplanted by KPD/APD‐LD while 50% benefited through prioritization of deceased donors in the modified kidney allocation system (KAS introduced in 2014). All APD transplanted groups had similar death‐censored 4‐year graft survivals as their relevant Organ Procurement and Transplantation Network (OPTN) groups. It is noteworthy that VHS graft and patient survival results were comparable to less sensitized and nonsensitized patients. All patients should be encouraged to search for compatible donors through different options. Expanding the donor pool through KPD and the new KAS of the OPTN increases the likelihood of transplantation for VHS patients.