A 40-year-old woman with HIV infection (CD4 count 120/μL, not on ART) presents with nephrotic syndrome and rapidly progressive renal failure. Renal biopsy shows collapsing focal segmental glomerulosclerosis (FSGS) with prominent tubuloreticular inclusions on electron microscopy. Which molecular mechanism underlies HIV-associated nephropathy (HIVAN)?
- A HIV infects podocytes and tubular cells, with viral genes vpr and nef causing podocyte dedifferentiation, proliferation, and loss of slit diaphragm proteins nephrin and podocin ✓
- B HIV envelope glycoprotein gp120 directly binds glomerular basement membrane, activating complement-mediated podocyte injury
- C HIV activates circulating soluble urokinase plasminogen activator receptor (suPAR) which binds glomerular αvβ3 integrin and disrupts podocyte cytoskeleton
- D HIV-mediated immune complex deposition in mesangium activates complement, causing membranoproliferative injury pattern
Explanation
HIVAN occurs in patients with APOL1 risk alleles (African ancestry) and is caused by direct HIV infection of podocytes and tubular cells. Viral genes, particularly vpr and nef, cause podocyte dedifferentiation (from mature differentiated cells to a proliferative precursor-like state), downregulation of nephrin and podocin at the slit diaphragm, and cytoskeletal collapse — producing the collapsing variant of FSGS. Tubuloreticular inclusions in endothelial cells reflect type I interferon stimulation. suPAR-αvβ3 integrin interaction is implicated in idiopathic FSGS, not HIVAN. HIV does not form typical immune complexes causing MPGN in HIVAN.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.