APOL1 allelic variants are associated with lower age of dialysis initiation and thereby increased dialysis vintage in African and Hispanic Americans with non-diabetic end-stage kidney disease

Abstract

Background: The APOL1 G1 and G2 genetic variants make a major contribution to the African ancestry risk for a number of common forms of non-diabetic end-stage kidney disease (ESKD). We sought to clarify the relationship of APOL1 variants with age of dialysis initiation and dialysis vintage (defined by the time between dialysis initiation and sample collection) in African and Hispanic Americans, diabetic and non-diabetic ESKD.

Methods: We examined APOL1 genotypes in 995 African and Hispanic American dialysis patients with diabetic and non-diabetic ESKD.

Results: The mean age of dialysis initiation for non-diabetic African-American patients with two APOL1 risk alleles was 48.1 years, >9 years earlier than those without APOL1 risk alleles (t-test, P=0.0003). Similar results were found in the non-diabetic Hispanic American cohort, but not in the diabetic cohorts. G1 heterozygotes showed a 5.3-year lower mean age of dialysis initiation (t-test, P=0.0452), but G2 heterozygotes did not show such an effect. At the age of 70, 92% of individuals with two APOL1 risk alleles had already initiated dialysis, compared with 76% of the patients without APOL1 risk alleles. Although two APOL1 risk alleles are also associated with ∼2 years increased in dialysis vintage, further analysis showed that this increase is fully explained by earlier age of dialysis initiation.

Conclusions: Two APOL1 risk alleles significantly predict lower age of dialysis initiation and thereby increased dialysis vintage in non-diabetic ESKD African and Hispanic Americans, but not in diabetic ESKD. A single APOL1 G1, but not G2, risk allele also lowers the age of dialysis initiation, apparently consistent with gain of injury or loss of function mechanisms. Hence, APOL1 mutations produce a distinct category of kidney disease that manifests at younger ages in African ancestry populations.