Clinical and genetic risk factors for apolipoprotein L1-mediated chronic kidney disease in people of African ancestry with HIV.

Abstract

To summarize current understanding of the epidemiology, pathogenesis and management of HIV-Associated Nephropathy (HIVAN) and other forms of Apolipoprotein L1 (APOL1)-mediated chronic kidney disease (CKD) in people of African ancestry with HIV. The G1 and G2 variants of the APOL1 gene, which have emerged in trypanosomiasis-endemic areas of Africa, predispose to HIV-associated nephropathy (HIVAN) and other forms of CKD. The risk of APOL1-mediated CKD is attenuated with HIV control and carriage of the p.N264K genetic variant. Several treatments targeting the APOL1 gene and the transmembrane ion channel encoded by the APOL1 gene are being evaluated in clinical trials; early findings indicate they achieve rapid and marked reductions in proteinuria in those with established APOL1-mediated CKD. Genetic variants of APOL1 are causally implicated in HIVAN and other forms of severe CKD in populations of African ancestry with HIV. Genetic, epigenetic and environmental factors influence the risk of developing APOL1-mediated CKD, and emerging APOL1-directed therapies offer the prospect of clinical remission to those with established APOL1-mediated CKD.