Equitable Transplantation: A Modifiable Risk Factor for Disparities in Mortality in ESKD
Authors: Marciana Laster, Keith C. Norris
Journal: Journal of the American Society of Nephrology (2022)

Racial disparities in survival and transplantation have been well described in both pediatric and adult ESKD populations. Black children with ESKD on dialysis have an increased risk of death when compared with their White peers.1,2 In a 2017 study of 12,123 children from the United States Renal Data System (USRDS) between 1995 and 2012, Ku et al.1 demonstrated a 36% higher risk of death in Black children on dialysis as compared with White children. These findings were abolished after adjustment for differential transplantation rates, underscoring the importance of transplantation access to racial differences in survival. Similarly, Laster et al.2 demonstrated 64% higher risk of mortality in Black compared with White children in an analysis of 2697 children from a large dialysis organization. This increased risk of mortality persisted despite accounting for differential transplantation rates. Contrary to pediatric studies, ESKD populations in adults have demonstrated a persistent and paradoxical survival advantage among Black adults treated with dialysis. This may reflect survival bias (relative health of those reaching dialysis) and/or racial differences in dialysis withdrawal, with Black patients being less likely to withdraw dialysis.3 Upon deeper inspection, the survival advantage evident in Black adults on dialysis is limited to middle age and older adults and is not present among younger adult populations.4,5 For instance, among 1,333,007 patients on incident dialysis in USRDS between 1995 and 2009, Kucirka et al.4 demonstrated a higher risk of death in Black patients 50 years or younger when compared with White patients. Notably, the greatest disparity in survival was seen among the age group 18–30 years, where Black patients had nearly twice the risk of death. Thus, the survival advantage of Black adult patients on dialysis seems to be limited to older age categories, whereas younger age adult categories demonstrate racial disparities in survival similar to those seen in pediatric ESKD. The study by Becerra et al.6 investigated 28,337 patients from USRDS with pediatric-onset ESKD who either started dialysis or received a transplant while younger than 18 years of age and were followed for as many as 30 years. This study design was unique in it allowed the assessment of outcomes well into the young adult period even for those beginning RRT at a very young age. Twenty-four percent of the cohort was reported as Black, but Hispanic ethnicity was not distinguished. An important novelty of this study was the use of a time-varying mediation analysis (survival mediational g formula) to simulate the extent to which racial disparities in 30-year overall survival would be reduced and how many Black lives would have been saved had they had the same transplant experience as White peers with similar confounders. When comparing Black with White participants, Becerra et al.6 demonstrated a 45% higher risk of death in Black participants and lower incidence of both first and second transplants. The disparities in transplantation resulted in 11% fewer total transplants over the 30-year period, including fewer patients ever receiving a transplant and fewer preemptive, living donor, and retransplants, resulting in 24% less time spent with a functioning transplant in Black as compared with White participants. Most notably, Becerra et al.6 estimated that ameliorating racial differences in the amount of time spent with a functioning transplant could prevent 35% of the excess death in young Black patients with ESKD. Although not accounting for the entire disparity, the work by Becerra et al.6 underscores the importance of striving for both equitable kidney transplant access and improvements in post-transplant graft survival among Black patients. Notably, they also found evidence of downstream effects of structural racism that may account for some of the unexplained 65% excess death among young Black patients with ESKD. These included being more likely to live in areas with low median household income and to have Medicaid as the primary payor. These factors along with distrust of the medical system and unmeasured effects of structural racism could conspire to produce reduced access to kidney transplantation and worse transplant outcomes. The findings of Becerra et al.6 expand upon those of Ku et al.1 by quantifying the contribution of differential transplantation rates and additionally, the contribution of differential transplantation outcomes to disparities in survival. It is well known that transplantation access is lower among Black and Hispanic children and adults.2,5 This disparity in access to transplantation contributes to longer time on dialysis and hence, longer exposure to risk factors for mortality. Still, access to transplantation is only the tip of the iceberg when it comes to long-term survival after ESKD. Even when transplant is achieved, both short- and long-term graft outcomes are consistently worse among Black when compared with White populations. For instance, in an analysis of 6216 pediatric patients with ESKD, Patzer et al.7 demonstrated that Black race was associated with higher rates of graft failure of both deceased and living donor transplants. This disparity persisted despite adjustment for immunologic factors, like peak panel reactive antibody, blood type, immunosuppression, and induction types. Thus, as highlighted by Becerra et al.,6 consideration of the potentially modifiable factor of time spent with a functioning transplant requires both consideration of time to transplant as well as short- and long-term graft outcomes. Although not the primary exposure of this study, it is important to acknowledge the patterns of survival and transplantation among Hispanic patients. Survival among Hispanic children and adults is consistently similar to or better than that of White patients, despite lower access to transplantation.1,2,5 Given this distinctly different mortality risk, parsing out Hispanic ethnicity within future studies of survival and transplantation may be necessary in order to avoid conflation of survival estimates and to explore racial and ethnic group–level dynamics, such social cohesion, internalized racism, weathering, and more that may affect survival.8 Ultimately, the work by Becerra et al.6 highlights the importance of equitable transplantation to disparities in ESKD survival. It specifically highlights the necessity of making strides toward increasing time spent with a functioning transplant to reduce racial disparities in young children with ESKD. Recent data suggest that following changes in the Kidney Allocation System in 2014, there have been improvements in transplant disparities, including equalization of time from dialysis to deceased donor transplant and longer times with a functioning graft in both Black and Hispanic pediatric patients.9 These data allow for more detailed discussions with parents regarding the long-term implications of having or not having transplantation and with policy makers to ensure that barriers in income, insurance, and other factors that affect access and adherence to transplant care are ameliorated. Time will reveal the effect of these improvements on overall patient survival. Disclosures K.C. Norris reports consultancy agreements with Atlantis Healthcare-Compliance, research and quality care for dialysis and CKD care in Puerto Rico; research funding from National Institutes of Health, State of California; advisory or leadership role with Ethnicity and Disease, JASN, CJASN, American Association of Medical Colleges, Atlantis Healthcare, American Association of Kidney Patients, National Kidney Foundation-Kidney Early Evaluation Program, International Society of Nephrology, ESRD Network Forum, and NIDDK Council; and other interests or relationships with AAKP, National Kidney Foundation, ESRD Network Forum, ASN, and Society of General Internal Medicine. The remaining author has nothing to disclose. Funding M. Laster is supported in part by National Institutes of Health grant K23DK123378. K.C. Norris is supported in part by National Institutes of Health grants P30AG021684, UL1TR000124, and P50MD017366.