Collapsing FSGS APOL1 Variant Prognosis — ESENeph MCQ

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HardGlomerulonephritisCollapsing FSGS APOL1 Variant PrognosisESENeph

A 25-year-old man presents with nephrotic syndrome. Renal biopsy shows segmental sclerosis with collapse of the glomerular capillary tuft and proliferation of overlying podocytes. He is of West African descent. HIV testing is negative. Genetic testing reveals two APOL1 high-risk alleles (G1/G2). What FSGS variant does this biopsy pattern represent?

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Correct answer: A — Collapsing variant

The collapsing variant of FSGS is characterised by segmental or global collapse of the glomerular capillary tuft with marked hypertrophy and hyperplasia of overlying podocytes. It carries the worst prognosis among FSGS variants, with rapid progression to ESKD and poor response to immunosuppressive therapy. Two copies of APOL1 high-risk alleles (G1 and/or G2, common in individuals of West African ancestry) confer markedly increased risk of collapsing FSGS, particularly when triggered by a 'second hit' (HIV, interferons, COVID-19). In the absence of a trigger, APOL1-associated collapsing FSGS may present idiopathically. The mechanism involves APOL1-mediated podocyte injury through endolysosomal dysfunction and inflammasome activation.

Reference: D'Agati et al 2011 – Columbia Classification; Kopp et al 2011 – APOL1 Kidney Disease