APOL1 Kidney Risk Variants and Long-Term Kidney Function in Healthy Middle-Aged Black Individuals: The Atherosclerosis Risk in Communities (ARIC) Study

Rationale and Objective Impact of Apolipoprotein L1(APOL1) genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established. Study Design Longitudinal cohort study. Setting & Participants 5,886 healthy individuals, 45-64 years old, enrolled in the Atherosclerosis Risk in Communities study with eGFRcr ≥ 80 mL/min who would be suitable kidney donors. Exposures Race and APOL1 genotype Outcomes EGFRcr-cys using CKD-EPI 2021 equation, uACR, proportion with CKD 3a or worse, ESKD and death. Analytical Approach Participants grouped on race and APOL1 genotype. Compared eGFRcr-cys and uACR across groups. Multinomial logistic regression models were used compare odds of CKD. Kaplan-Meier survival curves were created to compare rates of ESKD and death at last follow-up. Results There were 5,075 whites (86%), 701 Blacks carrying low-risk APOL1 genotype (12%) and 110 Blacks carrying high-risk APOL1 genotype (2%). The mean age at baseline was 53±6 years. At 10 years, white participants had lower eGFRcr-cys than low-risk and high-risk groups (89±16 vs. 91±16 and 92±15 mL/min/1.73m2, respectively; p <0.001). At 25 years, white participants continued to have lower eGFRcr-cys than low-risk group (70±18 vs. 72±19 mL/min/1.73m2; p <0.001) but not compared to high risk APOL1 genotype (67±23 mL/min/1.7m2). There was no difference in uACR among groups at 10 and 25 years (p=0.87 and 0.91 respectively). The odds of developing CKD Stage 3a or worse were not different between low-risk and high-risk APOL1 group in both unadjusted and adjusted models (p=0.26 and p=0.39, respectively). At last follow-up, < 5% developed ESKD and 45% of individuals either died or reached ESKD with no difference in outcomes between the groups. Limitations Low ascertainment due to death and long follow-up Conclusions Among middle-aged individuals, APOL1 genotype does not appear to be a major driver of future risk of kidney disease.