APOL1 and chronic kidney disease in pediatrics: a study from the Biorepository and Integrative Genomics Initiative

APOL1 variants confer increased risk for kidney disease in individuals of African ancestry, particularly in homozygous or compound heterozygous states. A missense variant, p.N264K, has been shown to attenuate this risk when co-inherited with the G2 allele. While these associations are established in adults, data in pediatric populations remain limited. Using the University of Tennessee Health Science Biorepository and Integrative Genomics initiative, we assessed chronic kidney disease (CKD) risk by APOL1 high-risk genotype and the potential protective effect of p.N264K in a diverse pediatric cohort.

This is a case-control study of African American children enrolled in the BIG initiative at Le Bonheur Children's Hospital (2014-2022). Composite CKD was defined by eGFR < 90 mL/min/1.73 m² or albuminuria (UACR > 30 mg/g) on two occasions ≥ 90 days apart. The p.N264K variant status was assessed in patients with APOL1 high-risk (HR). Logistic regression models adjusted for age, sex, and five principal components of ancestry assessed associations with CKD and albuminuria.

CKD cases had 8% higher odds of APOL1 HR status (Odds Ratio (OR): 1.08, 95% Confidence Interval (CI): 0.88-1.33). Stronger associations were observed in cases with albuminuria and APOL1 HR status (OR: 1.41, 95% CI: 1.02-1.92, p = 0.03). The p.N264K variant was detected in 4.3% of cases and 4.5% of controls, and appeared to attenuate CKD risk among HR individuals, though sample size limited statistical power.

APOL1 HR genotypes were associated with albuminuria in African American children. The p.N264K variant may modify this risk, warranting further study.