Clinical phenotype of APOL1 nephropathy in young relatives of patients with end-stage renal disease

Background: Two coding variants—G1 and G2—in the apolipoprotein L-1 (APOL1) gene are associated with increased incidence of end-stage renal disease (ESRD) in the adult African American population. These variants associate with hypertension-attributed renal disease, focal segmental glomerulosclerosis (FSGS), and HIV-associated nephropathy. We hypothesized that as a genetic disease, APOL1 nephropathy has a pediatric phenotype. Methods: We investigated the incidence of APOL1 variants in young African Americans with hypertension or FSGS and a family history of ESRD by conducting a case–control study of 93 pediatric and young adult African Americans with hypertension or FSGS to determine the association with APOL1 risk variants, G1, and G2 using custom-made TaqMan-based allelic discrimination assays. Results: Forty of the 61 cases (66 %) with a family history of kidney disease had two APOL1 risk variants, significantly higher than the prevalence in controls and the general African American population (p < 0.001); 24 of 29 patients with hypertension-attributed kidney disease had two APOL1 risk variants, while none of nine hypertensive patients without kidney disease had more than one risk allele. Conclusions: Although it was a small study cohort, our findings strongly suggest for the first time that two APOL1 risk alleles in young hypertensive African Americans with a family history of ESRD are strongly associated with kidney disease.