HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics

Abstract

Recently, an association was found between nondiabetic kidney disease in African Americans and two independent sequence variants in the APOL1 gene, encoding apolipoprotein L1. In this study we determined the frequency of APOL1 risk variants in patients with biopsy-proven HIV-associated nephropathy (HIVAN) and distinctive pathological characteristics potentially driven by those risk variants. Among 76 patients with HIVAN, 60 were successfully genotyped for APOL1 G1 and G2 polymorphisms. In this cohort, 37 had two risk alleles, 18 were heterozygous, and 5 had neither risk variant. There were no differences in the pathological findings of HIVAN and the number of APOL1 risk alleles. Further, the progression to end-stage kidney disease or death did not differ by the number of risk alleles. Median renal survival was 9.3 months in patients with zero or one risk allele compared to 11.7 months in patients with two APOL1 risk alleles. Thus, our study suggests that although the majority of African-American patients with HIVAN have two APOL1 risk alleles other as yet unknown factors in the host, including genetic risk variants and environmental or viral factors, may influence the development of this disorder in those with zero or one APOL1 risk allele.

Figure 1

Kaplan–Meier estimate of renal survival in two groups of study patients (0/1 APOL1 risk allele and 2 APOL1 alleles). Median renal survival was 9.3 months (IQR 3.6, 14.6) in patients with 0/1 APOL1 risk allele compared to 11.7 months (IQR 3.4, 24.5) in those with2 APOL1 risk alleles, p=0.31 (log rank test).

Figure 2

Kaplan–Meier estimate of survival in two groups of study patients (0/1 APOL1 risk allele and 2 APOL1 alleles). Median survival was 34.2 months (IQR 16.6, 77.1) in patients with 0/1 APOL1 risk allele compared to 20.1 months (IQR 12.5, 34.3) in those with2 APOL1 risk alleles, p=0.40 (log rank test).