HIV-associated nephropathy: a diagnosis in evolution

Abstract

HIV-1 associated nephropathy (HIVAN) is a clinical and renal histological disease characterized by the presence of heavy proteinuria associated with focal segmental glomerulosclerosis and microcystic tubular dilatation. These renal lesions lead to renal enlargement and rapid progression to kidney failure. People from African ancestry show a unique susceptibility to develop HIVAN. The study by Wearne and colleagues, which includes the largest group of patients of African ancestry with HIVAN studied so far, describes a novel renal histological variant of HIVAN, and suggests that antiretroviral therapies improve the clinical outcome of all HIV-associated renal diseases. These findings, when interpreted in the context of recent advances in our understanding of the molecular pathogenesis and genetics of HIVAN, will facilitate the recognition of all clinical variants of HIVAN as well the planning of better screening, prevention, and treatment programs for all HIV nephropathies.

Fig. 1.

Risk factors and pathogenesis of HIV-associated renal diseases. A longstanding high viral load is a major risk factor for the development of HIV-associated renal diseases. Immune activation and chronic inflammation are crucial features driving HIV replication and are additional risk factors for the development of HIV-associated renal diseases. Antiretroviral therapies (ART) block HIV-1 replication, decreasing the viral load and the chronic inflammatory changes (red lines). Untreated individuals of African ancestry carrying two risk variants of the APOL-1 gene are at very high risk of developing HIVAN. The incidence of HIVAN is reduced in a significant manner with ART. These drugs can also induce renal injury per se (red arrow). Other renal diseases may affect the clinical outcome of HIVAN. Some individuals develop HIVAN in combination with immune complex glomerulonephritis (HIVAN + ICGN). The APOL1 risk variants do not appear to play a direct role in the pathogenesis of HIV-associated immune complex glomerulonephritis (HIV-ICGN). HIV-1 affects several intrinsic renal cell types and induces different histological variants of HIVAN. The tubulointersitial lesions are the most consistent findings seen in patients with HIVAN and can predict an adverse clinical outcome. PEC, parietal epithelial cells; ICGN, immune complex glomerulonephritis.