Faculty Bibliography

Incompatible living donor kidney transplant (ILDKT) has been established as an effective option for end stage renal disease (ESRD) patients with willing but HLA incompatible live donors, reducing mortality and improving quality of life. Depending upon antibody titer, ILDKT can require highly resource intensive procedure including intravenous immunoglobulin, plasma exchange and/or cell depleting antibody treatment as well as protocol biopsies and DSA testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT recipients (N=926) with varying antibody titers to matched compatible transplants (N=2762) performed between 2002-2011. Data were assembled from a national cohort study of ILDKT and a unique dataset linking hospital cost accounting data, and Medicare claims. Overall, ILDKT transplants were 41% more expensive than their compatible counterparts ($151,024 vs. $106,636, p<.0001). The incremental cost varied by antibody titers: positive on Luminex assay but negative flow cytometric crossmatch 20% increase, positive flow cytometric crossmatch but negative cytotoxic crossmatch 26% increase, and positive cytotoxic crossmatch 39% increase (p<.0001 for all). ILDKT was associated with higher Medicare payments ($91,330 vs. $63,782 p<.0001), longer median length of stay (12.9 vs. 7.8 days), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplant

In 2013, the Organ Procurement and Transplantation Network (OPTN)/ United Network for Organ Sharing (UNOS) mandated that transplant centers collect data on living kidney donors (LKDs) at 6 months, 1 year, and 2 years postdonation, with policy-defined thresholds for the proportion of complete living donor follow-up (LDF) data submitted in a timely manner (60 days before or after the expected visit date). While mandated, it was unclear how centers across the country would perform in meeting thresholds, given potential donor and center-level challenges of LDF. To better understand the impact of this policy, we studied Scientific Registry of Transplant Recipients data for 31,615 LKDs between January 2010 and June 2015, comparing proportions of complete and timely LDF form submissions before and after policy implementation. We also used multilevel logistic regression to assess donor- and center-level characteristics associated with complete and timely LDF submissions. Complete and timely 2-year LDF increased from 33% prepolicy (January 2010 through January 2013) to 54% postpolicy (February 2013 through June 2015) (p < 0.001). In an adjusted model, the odds of 2-year LDF increased by 22% per year prepolicy (p < 0.001) and 23% per year postpolicy (p < 0.001). Despite these annual increases in LDF, only 43% (87/202) of centers met the OPTN/UNOS-required 6-month, 1-year, and 2-year LDF thresholds for LKDs who donated in 2013. These findings motivate further evaluation of LDF barriers and the optimal approaches to capturing outcomes after living donation.

Nondirected living donors (NDLDs) are an important and growing source of kidneys to help reduce the organ shortage. In its infancy, NDLD transplantation was clustered at a few transplant centers and rarely benefited African American (AA) recipients. However, NDLDs have increased 9.4-fold since 2000, and now are often used to initiate kidney paired donation chains. Therefore, we hypothesized that the initial geographic clustering and racial disparities may have improved. We used Scientific Registry of Transplant Recipients data to compare NDLDs and their recipients between 2008-2015 and 2000-2007. We found that NDLD increased an average of 12% per year, from 20 in 2000 to 188 in 2015 (IRR: 1.12, 95% CI: 1.11-1.13, P < .001). In 2000-2007, 18.3% of recipients of NDLD kidneys were AA; this decreased in 2008-2015 to 15.7%. NDLD transplants initially became more evenly distributed across centers (Gini 0.91 in 2000 to Gini 0.69 in 2011), but then became more clustered at fewer transplant centers (Gini 0.75 in 2015). Despite the increased number of NDLDs, racial disparities have worsened and the center-level distribution of NDLD transplants has narrowed in recent years.

In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

BACKGROUND:After kidney transplantation, early readmission is independently associated with graft loss and mortality. The mechanism of this association is poorly understood. Understanding the timeline of risk, that is, during the readmission hospitalization versus periods postreadmission, will provide additional insights. METHODS:We used national registry data to study 56 076 adult Medicare-primary first-time kidney transplant recipients from December 1999 to October 2011. Piecewise Cox proportional hazard models were used to estimate the association between graft loss, mortality, and readmission for 2 periods: readmission hospitalization and postreadmission. RESULTS:During the readmission hospitalization, graft loss was substantially higher (deceased donor kidney transplant [DDKT] without delayed graft function [DGF] hazard ratio: 24.634.447.9, P < 0.001; with DGF: 10.815.221.4, P < 0.001; live donor kidney transplant [LDKT]: 18.136.774.2, P < 0.001) and mortality was substantially higher (DDKT without DGF: 14.120.830.7, P < 0.001; with DGF: 9.0312.818.0, P < 0.001; LDKT: 9.0018.241.3, P < 0.001). Immediately after readmission discharge, graft loss (DDKT without DGF: 2.082.402.77, P < 0.001; with DGF: 1.832.142.51, P < 0.001; LDKT: 2.002.503.13, P < 0.001), and mortality (DDKT without DGF: 2.162.432.73, P < 0.001; with DGF: 1.832.162.88, P < 0.001; LDKT: 1.902.342.88, P < 0.001) remained elevated, but much less so. After readmission, the hazard of graft loss remained, but decreased 19% per year for DDKT recipients (time varying coefficient 0.780.810.85, P < 0.001) and 14% per year for LDKT recipients (0.790.860.93, P < 0.001). The hazard of mortality remained, but decreased 14% per year for DDKT recipients (0.830.860.89, P < 0.001) and 9% per year for LDKT recipients (0.850.910.98, P < 0.001). CONCLUSIONS:In conclusion, readmission is most strongly associated with graft loss and mortality during the readmission hospitalization, but also portends a lasting, albeit attenuated, risk postreadmission.

Studies have estimated the average risk of postdonation ESRD for living kidney donors in the United States, but personalized estimation on the basis of donor characteristics remains unavailable. We studied 133,824 living kidney donors from 1987 to 2015, as reported to the Organ Procurement and Transplantation Network, with ESRD ascertainment via Centers for Medicare and Medicaid Services linkage, using Cox regression with late entries. Black race (hazard ratio [HR], 2.96; 95% confidence interval [95% CI], 2.25 to 3.89; P<0.001) and male sex (HR, 1.88; 95% CI, 1.50 to 2.35; P<0.001) was associated with higher risk of ESRD in donors. Among nonblack donors, older age was associated with greater risk (HR per 10 years, 1.40; 95% CI, 1.23 to 1.59; P<0.001). Among black donors, older age was not significantly associated with risk (HR, 0.88; 95% CI, 0.72 to 1.09; P=0.3). Greater body mass index was associated with higher risk (HR per 5 kg/m², 1.61; 95% CI, 1.29 to 2.00; P<0.001). Donors who had a first-degree biological relationship to the recipient had increased risk (HR, 1.70; 95% CI, 1.24 to 2.34; P<0.01). C-statistic of the model was 0.71. Predicted 20-year risk of ESRD for the median donor was only 34 cases per 10,000 donors, but 1% of donors had predicted risk exceeding 256 cases per 10,000 donors. Risk estimation is critical for appropriate informed consent and varies substantially across living kidney donors. Greater permissiveness may be warranted in older black candidate donors; young black candidates should be evaluated carefully.

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count >/=500 cells/muL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates.