A 35-year-old HIV-positive African American man presents with nephrotic-range proteinuria. Renal biopsy shows collapsing variant of focal segmental glomerulosclerosis (FSGS) with podocyte hypertrophy and hyperplasia overlying collapsed and sclerotic glomerular tuft. Electron microscopy shows extensive podocyte foot process effacement and tubulo-reticular inclusions (TRIs) in endothelial cells. The pathogenesis most directly involves:

• A HIV-1 direct infection of podocytes and tubular cells causing APOL1 high-risk genotype-enhanced podocyte injury ✓
• B Immune complex deposition in the mesangium with complement activation causing podocyte injury
• C Anti-PLA2R antibodies targeting the podocyte surface and causing membranous nephropathy
• D T-cell-mediated permeability factor circulating systemically causing primary FSGS

Explanation

HIV-associated nephropathy (HIVAN) is the collapsing variant of FSGS seen almost exclusively in Black patients and strongly associated with APOL1 G1/G2 high-risk alleles. HIV-1 directly infects podocytes and tubular epithelial cells (which lack CD4 via alternative co-receptor use), causing dysregulated podocyte gene expression, loss of differentiation, and a proliferative phenotype resulting in collapse. TRIs in endothelial cells reflect type-1 interferon signaling, a hallmark of HIV infection. The APOL1 high-risk variants enhance susceptibility to HIVAN beyond HIV viremia alone. Immune complex deposition characterizes HIV immune complex disease of the kidney (HIVICK). Anti-PLA2R antibodies are the mechanism in idiopathic membranous nephropathy. T-cell permeability factor is implicated in primary FSGS.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.