Sickle Cell Trait and the Risk of ESRD in Blacks

Abstract

Blacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to <i>APOL1</i> high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown. In a large population-based cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated 9909 self-reported blacks (739 with SCT and 243 with hemoglobin C trait). Incident ESRD occurred in 40 of 739 (5.4%) individuals with SCT, six of 243 (2.5%) individuals with hemoglobin C trait, and 234 of 8927 (2.6%) noncarriers. The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT and 4.0 per 1000 person-years for noncarriers. Compared with individuals without SCT, individuals with SCT had a hazard ratio for ESRD of 2.03 (95% confidence interval, 1.44 to 2.84). Hemoglobin C trait did not associate with prevalent CKD or ESRD. The incidence rate for ESRD among participants with <i>APOL1</i> high-risk genotypes was 6.6 per 1000 person-years, with a hazard ratio for ESRD of 1.77 (95% confidence interval, 1.31 to 2.38) for participants with, compared with those without, <i>APOL1</i> high-risk genotypes. In this cohort, SCT strongly associated with risk of progression to ESRD in blacks, and this degree of risk for ESRD was similar to that conferred by <i>APOL1</i> high-risk genotypes. These results may have important public policy implications for genetic counseling of SCT carriers.