A 31-year-old man of West African ancestry with untreated HIV infection presents with rapidly progressive renal failure and nephrotic-range proteinuria. Ultrasound shows enlarged echogenic kidneys. Biopsy shows collapse of glomerular tufts with marked podocyte hyperplasia, accompanied by microcystic dilatation of tubules containing proteinaceous casts and tubuloreticular inclusions on electron microscopy. Which genetic factor best explains his markedly increased susceptibility?

• A CFH mutation causing uncontrolled alternative complement activation
• B Two APOL1 risk alleles (G1/G2) ✓
• C Heterozygous COL4A3 mutation
• D UMOD mutation encoding uromodulin

Explanation

Collapsing glomerulopathy in the setting of HIV infection (HIV associated nephropathy) shows a striking predilection for individuals of recent West African ancestry, explained by carriage of two APOL1 risk variants (G1 and G2) that confer strong genetic risk for FSGS and HIVAN. Tubuloreticular inclusions reflect interferon exposure from HIV. Complement factor H mutations underlie atypical HUS and C3 glomerulopathy, while UMOD mutations cause autosomal dominant tubulointerstitial kidney disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.