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.     

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.     

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.     

Expanding Kidney Paired Donation Through Participation by Compatible Pairs

In kidney paired donation (KPD), incompatible pairs exchange kidneys so that each recipient receives a compatible organ. This modality is underutilized partly because of the difficulty of finding a suitable match among incompatible pairs. Alternatively, recipients with compatible donors might enter KPD arrangements in order to be matched with a donor predicted to give greater allograft durability or for other altruistic reasons. Using simulated donors and recipients, we investigated the impact of allowing recipients and their compatible donors to participate in KPD. For KPD programs of any size, the participation of compatible donor/recipient pairs nearly doubled the match rate for incompatible pairs (28.2% to 64.5% for single-center program, 37.4% to 75.4% for national program). Legal, logistical, and governmental controversies have hampered the expansion of KPD in the United States by delaying the creation of a national program. The inclusion of compatible pairs into small single-center pools could achieve match rates that would surpass that which could be realized by a national list made up of only incompatible pairs. This new paradigm of KPD can immediately be instituted at the single-center level, while the greatest gains will be achieved by incorporating compatible pairs into a national program.     

Altruistic Donor Triggered Domino‐Paired Kidney Donation for Unsuccessful Couples from the Kidney‐Exchange Program

Between January 2000 and July 2009, 132 individuals inquired about altruistic kidney donation to strangers. These donors were willing to donate to genetically and emotionally unrelated patients. Some altruistic donors wished to donate to a specific person, but most wished to donate anonymously. In domino‐paired donation, the altruistic donor donates to the recipient of an incompatible couple; the donor of that couple (domino‐donor) donates to another couple or to the waiting list. In contrast to kidney‐exchange donation where bilateral matching of couples is required, recipient and donor matching are unlinked in domino‐paired donation. This facilitates matching for unsuccessful couples from the kidney‐exchange program where blood type O prevails in recipients and is under‐represented in donors. Fifty‐one altruistic donors (39%) donated their kidney and 35 domino‐donors were involved. There were 29 domino procedures, 24 with 1 altruistic donor and 1 domino‐donor, 5 with more domino‐donors. Eighty‐six transplantations were performed. Donor and recipient blood type distribution in the couples limited allocation to blood type non‐O waiting list patients. The success rate of domino‐paired donation is dependent on the composition of the pool of incompatible pairs, but it offers opportunities for difficult to match pairs that were unsuccessful in the kidney‐exchange program.     

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.     

Broken Chains and Reneging: A Review of 1748 Kidney Paired Donation Transplants

Concerns regarding the potential for broken chains and “reneges” within kidney paired donation (KPD) and its effect on chain length have been raised previously. Although these concerns have been tested in simulation studies, real‐world data have yet to be evaluated. The purpose of this study was to evaluate the actual rate and causes of broken chains within a large KPD program. All patients undergoing renal transplantation through the National Kidney Registry from 2008 through May 2016 were included for analysis. Broken chains and loops were identified. A total of 344 chains and 78 loops were completed during the study period, yielding a total of 1748 transplants. Twenty broken chains and one broken loop were identified. The mean chain length (number of transplants) within broken chains was 4.8 compared with 4.6 of completed chains (p = 0.78). The most common causes of a broken chain were donor medical issues incurred while acting as a bridge donor (n = 8), donors electing not to proceed (n = 6), and kidneys being declined by the recipient surgeon (n = 4). All recipients involved in a broken chain subsequently received a transplant. Based on the results, broken chains are infrequent, are rarely due to lack of donor motivation, and have no significant impact on chain length.     

Characterization of Waiting Times in a Simulation of Kidney Paired Donation

A national kidney paired donation (KPD) program will substantially increase transplant opportunities for recipients with blood type incompatible or cross-match positive donors. It seems likely that donor-recipient pairs with certain blood types, races or restrictions will wait longer than others for a match, although no data exist to confirm this assumption. We simulated patients and characterized the predicted waiting times for different blood type sub-groups, as well as the effects of patient-imposed restrictions on waiting time. We also compared waiting times of different racial sub-groups. Almost all patients with panel-reactive antibody (PRA) less than 80% match within a few months in a national KPD program, with the longest waiting time seen by O recipients with AB donors. Highly sensitized patients wait considerably longer, especially those unwilling to travel or accept older donors, and those with AB or B donors may not match in a timely manner. Although patients are better served by matching in a combined pool than within their own race, racial inequalities exist and bonus points can offset some of these differences. These data provide the first waiting time predictions that can aid patients with incompatible donors in choosing between KPD and desensitization, and can also facilitate planning for a national KPD program.     

A Comparison of Populations Served by Kidney Paired Donation and List Paired Donation

Options for utilizing live donor kidneys from those who are blood type incompatible or crossmatch positive with their intended recipients include kidney paired donation (KPD), list paired donation (LPD) and desensitization. KPD provides live donor kidneys for both recipients but requires a match to another incompatible pair, while LPD utilizes the deceased donor pool but is restricted by ethical and logistic concerns. We simulated patients and their potential donors to determine which recipients could receive a kidney through KPD and LPD. With smaller populations (100 pairs or fewer), more kidneys were matched through LPD, although the greatest benefit was derived from a combination of LPD and KPD. With increasing population sizes, more patients were matched through KPD, including almost all patients who would have been eligible for LPD. At population sizes predicted to be achieved by a national paired donation system, the role of LPD became minimal, with only 3.9% of pairs unmatched through KPD eligible for LPD. Considerable overlap was seen between the pairs unmatchable by KPD and those ineligible for LPD, namely less-demanded donors and hard-to-match recipients. For this population, the best option may be desensitization.     

Clinical Outcomes of Multicenter Domino Kidney Paired Donation

Domino kidney paired donation (KPD) is a method by which an altruistic living nondirected donor (LND) is allocated to a pool of incompatible donor–recipient pairs (DRP) and a series of KPDs is initiated. To evaluate the feasibility and clinical outcomes of multicenter domino KPD, we retrospectively analyzed a cohort of DRPs who underwent domino KPD between February 2001 and July 2007 at one of 16 transplant centers. One hundred seventy-nine kidney transplants were performed, with 70 domino chains initiated by altruistic LND. There were 45 two-pair chains, 15 three-pair chains, 7 four-pair chains, 2 five-pair chains and 1 six-pair chain. A majority of donors were spouses (47.5%) or altruistic LNDs (39.1%). DRPs with a blood type O recipient or an AB donor comprised 45.9% of transplanted DRPs. HLA mismatch improved in transplanted donors compared to intended donors in pairs enrolled to improve HLA mismatch (3.4 ± 0.7 vs. 4.8 ± 1.0, p < 0.001). One-year and 5-year graft survival rates were 98.3% and 87.7%, respectively, with a median follow-up of 46 months. One-year and 5-year patient survival rates were 97.2% and 90.8%, respectively. In conclusion, multicenter domino KPD could multiply the benefits of donation from LNDs, with patients and graft survival rates comparable to those seen with conventional KPD.     

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.     

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.     

Reciprocity to Increase Participation of Compatible Living Donor and Recipient Pairs in Kidney Paired Donation

Inclusion of compatible living donor and recipient pairs (CPs) in kidney paired donation (KPD) programs could increase living donor transplantation. We introduce the concept of a reciprocity‐based strategy in which the recipient of a CP who participates in KPD receives priority for a repeat deceased donor transplant in the event their primary living donor KPD transplant fails, and then we review the practical and ethical considerations of this strategy. The strategy limits prioritization to CPs already committed to living donation, minimizing the risk of unduly influencing donor behavior. The provision of a tangible benefit independent of the CP's actual KPD match avoids many of the practical and ethical challenges with strategies that rely on finding the CP recipient a better‐matched kidney that might provide the CP recipient a future benefit to increase KPD participation. Specifically, the strategy avoids the potential to misrepresent the degree of future benefit of a better‐matched kidney to the CP recipient and minimizes delays in transplantation related to finding a better‐matched kidney. Preliminary estimates suggest the strategy has significant potential to increase the number of living donor transplants. Further evaluation of the acceptance of this strategy by CPs and by waitlisted patients is warranted.     

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.     

Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation

We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.