Podocyte injury in HIV-associated nephropathy

Prior to the widespread use of antiretroviral therapy, HIV-associated nephropathy (HIVAN) was the leading cause of end-stage renal disease among individuals of African descent. HIVAN, a rapidly progressing glomerulopathy, is characterized by collapsing focal segmental glomerulosclerosis, podocyte hypertrophy, and proliferation of epithelial cells overlying the Bowman's space. Although the origin of these proliferating cells is debatable, a large body of evidence suggests that podocyte dysfunction occurs in HIVAN. In the last decade, several groups have demonstrated that the podocyte serves as a reservoir for the virus and podocyte dysfunction is a direct result of specific viral protein expression. The viral protein, nef, directly activates several signaling pathways, resulting in podocyte dedifferentiation and proliferation. Today, with the widespread use of antiretroviral therapy, classical HIVAN is rare. Nonetheless, as patients with chronically infected HIV live longer, many still succumb to chronic kidney disease due to coexisting illnesses such as diabetes and hypertension. However, it remains unclear whether this viral reservoir serves a medium for development of non-HIVAN-related kidney diseases such as diabetic nephropathy. We also provide some insights into potential areas of research in characterizing podocyte biology in this changing spectrum of HIV-related kidney disease.