An 8-year-old boy of African ancestry presents with rapidly progressive nephrotic syndrome unresponsive to corticosteroids. Biopsy shows collapse of glomerular capillary tufts with marked hypertrophy and hyperplasia of visceral epithelial cells filling Bowman space, resembling a crescent. Serum HIV testing is positive. The variant of focal segmental glomerulosclerosis seen here and its strong genetic association are:

• A Collapsing variant, association with APOL1 risk alleles ✓
• B Perihilar variant, association with APOL1 risk alleles
• C Tip lesion variant, association with NPHS2 (podocin)
• D Cellular variant, association with TRPC6 mutation

Explanation

Collapsing glomerulopathy, the most aggressive FSGS variant, shows tuft collapse with striking podocyte proliferation and is strongly associated with HIV infection and with interferon therapy. Two APOL1 risk alleles (G1 and G2), carried at high frequency in individuals of West African ancestry, markedly increase susceptibility to this pattern. The tip lesion has the best prognosis among Columbia variants, and TRPC6 mutation causes adult-onset autosomal dominant FSGS without collapse.

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.