title: HIV-associated nephropathy: pathogenesis.
abstract: OBJECTIVE
  HIV-associated nephropathy (HIVAN) is characterized histologically by a collapsing form of focal segmental glomerulosclerosis (FSGS), microcystic tubular dilation, interstitial inflammation and fibrosis. In this review, we provide a summary of the current state of knowledge about the mechanisms involved in the pathogenesis of HIVAN.
  
  
  RESULTS
  Two variants in the ApoL1 gene have been identified as the susceptibility alleles that account for a majority of the increased risk of FSGS and nondiabetic end-stage renal disease in blacks. HIVAN1 and HIVAN2 are the other host susceptibility genes that have been identified in animal models for HIVAN. HIV infects renal tubular epithelial cells likely through direct cell-cell transmission. Both in-vivo and in-vitro evidence suggests that Nef and Vpr are the key viral genes mediating HIVAN. Nef induces podocyte dysfunction, whereas Vpr induces renal tubular epithelial cell apoptosis.
  
  
  CONCLUSIONS
  HIVAN results from direct infection by HIV-1 and expression of viral genes, especially Nef and Vpr, in renal epithelial cells in a genetically susceptible host. The infected renal epithelium acts as a separate viral compartment from the blood and facilitates evolution of strains distant from blood. Dysregulation of several host cellular pathways, including those involved in cell cycle and apoptosis, ultimately results in the unique histopathological syndrome of HIVAN.
authors.affiliation: Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Medapalli
authors.forename: John C
authors.initials: JC
authors.lastname: He
authors.forename: Paul E
authors.initials: PE
authors.lastname: Klotman
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000209:etiology* / Q000235:genetics; D000818:Animals; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics; D020409:Molecular Motor Proteins / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics; D009395:Nephritis, Interstitial / Q000209:etiology; D050199:Podocytes / Q000166:cytology / Q000502:physiology
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains