Race, APOL1 Risk, and eGFR Decline in the General Population

Abstract

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.

Keywords: end-stage renal disease; ethnicity; glomerular filtration rate.

Figure 1.

Median, 10th, and 90th percentile eGFR decline from mean baseline eGFR over 25 years varied by race/APOL1 status. Slopes were estimated from a mixed model with the following covariates: age, sex, baseline coronary heart disease, body mass index, HDL cholesterol, diabetes, systolic BP, smoking, family income, and education level, and interaction terms of each covariate with time.

Figure 2.

Distribution of average yearly eGFR slopes varied by race/APOL1 status. eGFR was imputed as 15 ml/min per 1.73 m² at the time of ESRD onset. (A) reflects the unadjusted slope distribution, (B) reflects the adjusted slope distribution with slopes estimated from a mixed model with the following additional covariates: age, sex, baseline coronary heart disease, body mass index, HDL cholesterol, diabetes, systolic BP, smoking, family income, and education level, and incorporating interaction terms of each covariate with time.