Apolipoprotein L1 genetic testing, family history of hypertension, and kidney disease in a Midwestern U.S. cohort

Background Understanding how family history and genetic factors—particularly apolipoprotein L1 ( APOL1 ) renal risk variants (RRVs)—contribute to kidney disease risk among Black individuals continues to evolve. Methods In a cohort of prospectively enrolled Black adults who underwent APOL1 genotyping and completed surveys at a Midwestern U.S. academic hospital (01/24/2019–03/21/2025; NCT05656261), we examined APOL1 RRV distribution in relation to family history, baseline clinical factors, and 3-month renal function change. Results Among 220 eligible participants, 17% (37/220) carried APOL1 high-risk genotypes (two RRVs). Family history of hypertension alone was reported by 37% (81/220), kidney disease alone by 3% (6/220), and both by 49% (109/220). High-risk genotypes were more common among those with both hypertension and kidney disease in their family (18%) versus those without either (12%). High-risk APOL1 genotype prevalence rose with increasing antihypertensive medication use (24% among those prescribed ≥4 agents) and was higher among individuals with lower race-free estimated glomerular filtration rate (eGFR) or albuminuria. Among 173 participants with eGFR values at 3-months, high-risk genotypes were more frequent among those with eGFR decline versus improvement (23% vs. 12%). Conclusion APOL1 high-risk genotypes were more common among individuals with a family history of hypertension and/or kidney disease, greater medication burden, lower kidney function, and early eGFR decline. The partial overlap between genetic and familial risk underscores the complex interplay of inherited, clinical, and environmental factors. Continued study and integrative strategies are needed to refine kidney disease risk stratification, enhance early identification, and guide prevention and treatment in at-risk populations.