Faculty Bibliography

Kidney paired donation represented 10% of living kidney donation in the United States in 2011. National registries around the world and several separate registries in the United States arrange paired donations, although with significant variations in their practices. Concerns about ethical considerations, clinical advisability, and the quantitative effectiveness of these approaches in paired donation result in these variations. For instance, although donor travel can be burdensome and might discourage paired donation, it was nearly universal until convincing analysis showed that living donor kidneys can sustain many hours of cold ischemia time without adverse consequences. Opinions also differ about whether the last donor in a chain of paired donation transplants initiated by a nondirected donor should donate immediately to someone on the deceased donor wait-list (a domino or closed chain) or should be asked to wait some length of time and donate to start another sequence of paired donations later (an open chain); some argue that asking the donor to donate later may be coercive, and others focus on balancing the probability that the waiting donor withdraws versus the number of additional transplants if the chain can be continued. Other controversies in paired donation include simultaneous versus nonsimultaneous donor operations, whether to enroll compatible pairs, and interactions with desensitization protocols. Efforts to expand public awareness of and participation in paired donation are needed to generate more transplant opportunities.

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.

Liver transplantation has evolved over the past four decades into the most effective method to treat end-stage liver failure and one of the most expensive medical technologies available. Accurate understanding of the financial implication of recipient severity of illness is crucial to assessing the economic impact of allocation policies. A novel database of linked clinical data from the Organ Procurement and Transplantation Network with cost accounting data from the University HealthSystem Consortium was used to analyze liver transplant costs for 15,813 liver transplants. This data was then utilized to consider the economic impact of alternative allocation systems designed to increase sharing of liver allografts using simulation results. Transplant costs were strongly associated with recipient severity of illness as assessed by the MELD score (p < 0.0001); however, this relationship was not linear. Simulation analysis of the reallocation of livers from low MELD patients to high MELD using a two-tiered regional sharing approach (MELD 15/25) resulted in 88 fewer deaths annually at estimated cost of $17,056 per quality-adjusted life-year saved. The results suggest that broader sharing of liver allografts offers a cost-effective strategy to reduce the mortality from end stage liver disease.

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 $12,000 to the cost of transplantation and nearly $22,000 to posttransplant costs in comparison to the lowest risk donors. Among the individual components of the DRI, donation after cardiac death (increased costs by $20,769 versus brain dead donors) had the greatest impact on transplant costs. Overall, 1-year costs were increased in older donors, minority donors, nationally shared organs, and those with cold ischemic times of 7-13 hours (P < 0.05 for all). In conclusion, donor quality, as measured by the DRI, is an independent predictor of LT costs in the perioperative and postoperative periods. Centers in highly competitive regions that perform transplantation on higher MELD patients with high DRI livers may be particularly affected by the synergistic impact of these factors.

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.

Living donor kidney exchange, also referred to as kidney paired donation (KPD), is a relatively new transplant modality that is growing by leaps and bounds in the U.S. From its first realization as an exchange of kidneys between two incompatible donor/recipient pairs, KPD has expanded to include compatible pairs, nondirected donors, three-way and larger exchanges, and living/deceased donor exchanges. Innovations both clinical (transporting organs instead of donors, and improved HLA screening) and mathematical (simulation to test policies, optimization to find better and more matches) have made this modality even more useful and accessible. There are several independent multi-center paired donation registries and many more single-center registries operating in the U.S., but incompatible pairs are most likely to match when they participate in the largest possible paired exchange pool; a single, unified KPD program in the United States would likely best serve patients in search of matches.

BACKGROUND AND OBJECTIVES/OBJECTIVE: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/METHODS: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). Cox's 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.

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.