Sommer E. Gentry

Domino paired kidney donation: a strategy to make best use of live non-directed donation

Current models for allocation of kidneys from living non-directed donors Living non-directed (LND) donors, also known as altruistic, good Samaritan, anonymous, or benevolent community donors, are a new and rapidly growing source of solid organs for transplantation. The willingness of individuals to donate organs without a designated recipient has been unexpected, but has probably developed as a societal response to the growing crisis in organ availability. In the context of this shortage, health professionals have attempted to make the best use of kidneys from LND donors. We present a novel application of paired donation that has the potential to multiply the number of recipients who can benefi t from each LND donation. At present, there is no universally accepted system for allocation of organs from LND donors. Selection of recipients has been at the discretion of the transplant centres where LND donors have presented and has generally been guided by one of three models: donorcentric, recipient-centric, or sociocentric allocation. Each of these models is supported by valid ethical arguments. The main goal of donor-centric allocation is to ensure a successful outcome for the recipient. A good outcome provides justifi cation for medical professionals to assist a person who is not ill to put themselves in harm’s way to aid another. A positive result also gives an LND donor a sense that their eff ort was fruitful and worthwhile. However, this model dictates allocation to the healthiest patient on the transplant waiting list. These recipients are the most likely to have good outcomes on dialysis or with organs from deceased donors, and therefore are arguably the least in need. Recipient-centric allocation is based on the belief that society has a responsibility to protect its most vulnerable and disadvantaged members. Under this model, organs from LND donors are given to those patients in the greatest need, those for whom a kidney transplant might be truly life saving, or those disadvantaged under the existing system for allocation of kidneys from deceased donors. This model mainly benefi ts children, patients who have no vascular access, highly sensitised patients, and those with life-threatening medical illnesses related to dialysis. However, because the recipient-centric model accords priority to such patients, it tends to yield unacceptably poor transplant outcomes, and could lead to a negative public perception of LND donation. Under the third model, of sociocentric allocation, the LND donated organ is treated as a public resource that should be allocated in the fairest and most equitable way, irrespective of outcome or need. This rationale dictates that the recipient should be the patient at the top of the transplant waiting list administered by the United Network of Organ Sharing (UNOS). UNOS oversees the allocation of deceased donor organs in the USA, using a so-called match run algorithm that ranks potential recipients according to agreed criteria. The limitations of this model are that a patient at the top of the list will probably receive a kidney from a deceased donor in the near future, and that they will have already incurred the costs, and exposure to comorbidity, that result from a long period on dialysis. The waiting list for deceased donor kidneys can be circumvented by patients who fi nd a willing live donor. But direct donation might be complicated by diff erences in blood type and by HLA sensitivity. Some incompatible donor-recipient pairs enter into programmes that facilitate paired donation, also known as kidney paired donation. A donor and recipient who have incompatible blood groups or HLA sensitivity can be matched with another incompatible pair, to result in two compatible transplants (fi gure). Although there are many ways to match up a pool of incompatible pairs, the mathematical technique of optimisation helps to fi nd out which matches will yield the best results. Nevertheless, even in paired-donation programmes in which mathematical optimisation is applied, more than 50% of the incompatible pairs in the pool remain unmatched. In many cases, pools of incompatible donor-recipient pairs have a high proportion of patients with blood types that are hard to match and those with HLA sensitisation.

MELD Exceptions and Rates of Waiting List Outcomes

Model for End‐stage Liver Disease (MELD)‐based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0–21.4% at the OPO‐level and 11.9–18.8% at the region level; proportion receiving an exception for other conditions was 0.0%–13.1% (OPO‐level) and 3.7–9.5 (region‐level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio [OR] = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.

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.

The Interplay of Socioeconomic Status, Distance to Center, and Interdonor Service Area Travel on Kidney Transplant Access and Outcomes

BACKGROUND AND OBJECTIVES Variation in kidney transplant access across the United States may motivate relocation of patients with ability to travel to better-supplied areas. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined national transplant registry and U.S. Census data for kidney transplant candidates listed in 1999 to 2009 with a reported residential zip code (n = 203,267). Coxs regression was used to assess associations of socioeconomic status (SES), distance from residence to transplant center, and relocation to a different donation service area (DSA) with transplant access and outcomes. RESULTS Patients in the highest SES quartile had increased access to transplant compared with those with lowest SES, driven strongly by 76% higher likelihood of living donor transplantation (adjusted hazard ratio [aHR] 1.76, 95% confidence interval [CI] 1.70 to 1.83). Waitlist death was reduced in high compared with low SES candidates (aHR 0.86, 95% CI 0.84 to 0.89). High SES patients also experienced lower mortality after living and deceased donor transplant. Patients living farther from the transplant center had reduced access to deceased donor transplant and increased risk of post-transplant death. Inter-DSA travel was associated with a dramatic increase in deceased donor transplant access (HR 1.94, 95% CI 1.88 to 2.00) and was predicted by high SES, white race, and longer deceased-donor allograft waiting time in initial DSA. CONCLUSIONS Ongoing disparities exist in kidney transplantation access and outcomes on the basis of geography and SES despite near-universal insurance coverage under Medicare. Inter-DSA travel improves access and is more common among high SES candidates.

Addressing Geographic Disparities in Liver Transplantation Through Redistricting

Severe geographic disparities exist in liver transplantation; for patients with comparable disease severity, 90‐day transplant rates range from 18% to 86% and death rates range from 14% to 82% across donation service areas (DSAs). Broader sharing has been proposed to resolve geographic inequity; however, we hypothesized that the efficacy of broader sharing depends on the geographic partitions used. To determine the potential impact of redistricting on geographic disparity in disease severity at transplantation, we combined existing DSAs into novel regions using mathematical redistricting optimization. Optimized maps and current maps were evaluated using the Liver Simulated Allocation Model. Primary analysis was based on 6700 deceased donors, 28 063 liver transplant candidates, and 242 727 Model of End‐Stage Liver Disease (MELD) changes in 2010. Fully regional sharing within the current regional map would paradoxically worsen geographic disparity (variance in MELD at transplantation increases from 11.2 to 13.5, p = 0.021), although it would decrease waitlist deaths (from 1368 to 1329, p = 0.002). In contrast, regional sharing within an optimized map would significantly reduce geographic disparity (to 7.0, p = 0.002) while achieving a larger decrease in waitlist deaths (to 1307, p = 0.002). Redistricting optimization, but not broader sharing alone, would reduce geographic disparity in allocation of livers for transplant across the United States.

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.

Kidney Paired Donation: Fundamentals, Limitations, and Expansions

Incompatibility between the candidate recipient and the prospective donor is a major obstacle to living donor kidney transplant. Kidney paired donation (KPD) can circumvent the incompatibility by matching them to another candidate and living donor for an exchange of transplants such that both transplants are compatible. KPD has faced legal, logistical, and ethical challenges since its inception in the 1980s. Although the full potential of this modality for facilitating transplant for individuals with incompatible donors is unrealized, great strides have been made. In this review article, we detail how several impediments to KPD have been overcome to the benefit of ever greater numbers of patients. Limitations and questions that have been addressed include blood group type O imbalance, reciprocal match requirements, simultaneous donor nephrectomy requirements, combining KPD with desensitization, the role of list-paired donation, geographic barriers, legal barriers, concerns regarding living donor safety, fragmented registries, and inefficient matching algorithms.

Cold ischemia time and allograft outcomes in live donor renal transplantation : Is live donor organ transport feasible?

One of the greatest obstacles to the implementation of regional or national kidney paired donation programs (KPD) is the need for the donor to travel to their matched recipients hospital. While transport of the kidney is an attractive alternative, there is concern that prolonged cold ischemia time (CIT) would diminish the benefits of live donor transplantation (LDTx). To examine the impact of increased CIT in LDTx, 1‐year serum creatinine (SCr), delayed graft function (DGF), acute rejection (AR) and allograft survival (AS) were analyzed in 38 467 patients by 2 h CIT groups (0–2, 2–4, 4–6 and 6–8 h) using data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN). Adjusted probabilities of DGF and AR were estimated in multivariate logistic regression models and AS was examined in multivariate Cox proportional hazards models. Although some increase in DGF was observed between the 0–2 h (4.7%) and 4–6 h (8.3%) groups, prolonged CIT did not result in inferior SCr, increased AR or compromised AS in any group with >2 h CIT compared with the 0–2 h group. Comparable long‐term outcomes for these grafts suggests that transport of live donor organs may be a feasible alternative to donor travel in KPD regions where CIT can be limited to 8 h.

The interaction among donor characteristics, severity of liver disease, and the cost of liver transplantation

Accurate assessment of the impact of donor quality on liver transplant (LT) costs has been limited by the lack of a large, multicenter study of detailed clinical and economic data. A novel, retrospective database linking information from the University HealthSystem Consortium and the Organ Procurement and Transplantation Network registry was analyzed using multivariate regression to determine the relationship between donor quality (assessed through the Donor Risk Index [DRI]), recipient illness severity, and total inpatient costs (transplant and all readmissions) for 1 year following LT. Cost data were available for 9059 LT recipients. Increasing MELD score, higher DRI, simultaneous liver–kidney transplant, female sex, and prior liver transplant were associated with increasing cost of LT (P < 0.05). MELD and DRI interact to synergistically increase the cost of LT (P < 0.05). Donors in the highest DRI quartile added close to

The roles of dominos and nonsimultaneous chains in kidney paired donation

12,000 to the cost of transplantation and nearly