A 25-year-old man with HIV infection presents with nephrotic syndrome. Renal biopsy shows collapsing focal segmental glomerulosclerosis (FSGS). Electron microscopy reveals tubuloreticular inclusions in endothelial cells. What is the pathogenic mechanism specific to HIV-associated nephropathy (HIVAN)?

• A Immune complex deposition in subepithelial space activating complement-mediated podocyte injury
• B HIV Nef and Vpr proteins directly infect podocytes and tubular cells, causing dysregulated proliferation and apoptosis ✓
• C Antiretroviral drug nephrotoxicity causing tubular mitochondrial dysfunction
• D HIV-induced dysregulation of VEGF receptors in podocytes

Explanation

HIVAN has a direct viral pathogenic mechanism: HIV infects podocytes and tubular epithelial cells (confirmed by in situ hybridisation for viral RNA), and HIV accessory proteins Nef and Vpr dysregulate cell cycle and induce apoptosis in these cells, leading to podocyte loss and the characteristic collapsing glomerulopathy. This explains why HIVAN predominantly affects individuals of African ancestry (APOL1 risk variants in podocytes amplify the injury). Tubuloreticular inclusions in endothelium are an interferon response marker, not immune complex deposits.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.