Survival Advantage of African American Dialysis Patients with End-Stage Renal Disease Causes Related to APOL1

Abstract

Background: Observational studies show that African American (AA) dialysis patients have longer survival than European Americans. We hypothesized that apolipoprotein L1 (APOL1) genetic variation, associated with nephropathy in AAs, contributes to the survival advantage in AA dialysis patients. Methods: We examined the association between race and mortality among 37,097 adult dialysis patients, including 54% AAs and 46% European Americans from a large dialysis organization (entry period from July 2001 to June 2006, follow-up through June 2007), within each cause of end-stage renal disease (ESRD) category associated with APOL1 renal risk variants using Cox proportional hazard models. Results: AA dialysis patients had numerically lower mortality than their European American counterparts for all causes of ESRD. The mortality reduction among AAs compared to European Americans was statistically significant in patients with ESRD attributed to diabetes mellitus, hypertension, and APOL1-enriched glomerulonephritis (GN) (HR [95% CI]: 0.69 [0.66–0.72], 0.73 [0.68–0.79], and 0.89 [0.79–0.99], respectively); these are conditions in which APOL1 variants promote kidney disease. By contrast, the significant survival advantage of AA dialysis patients was not observed in patients with ESRD attributed to other kidney disease (including polycystic kidney disease, interstitial nephritis, and pyelonephritis) and other GN, which are not associated with APOL1 variants. Conclusions: These data suggest the hypothesis that the relative survival advantage of AA dialysis patients may be related to APOL1 variation. Further large population-based genetic studies are required to test this hypothesis.