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APOL1 Collapsing FSGS — ESENeph MCQ

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HardGlomerulonephritisAPOL1 Collapsing FSGSESENeph

A 30-year-old man of West African descent presents with collapsing FSGS and nephrotic syndrome. HIV testing is negative. Genetic testing reveals high-risk APOL1 genotype (G1/G2). What is the clinical significance?

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Correct answer: D — High-risk APOL1 variants (G1 and G2) strongly predispose to FSGS, HIVAN, and hypertensive nephrosclerosis in individuals of African ancestry; they confer protection against Trypanosoma brucei

APOL1 risk variants (G1 and G2) are present in approximately 13% of African Americans (two copies of risk alleles). They confer a 7-10 fold increased risk of FSGS, hypertensive nephrosclerosis, and HIVAN. The high-risk alleles are maintained at high frequency because they provide protection against Trypanosoma brucei rhodesiense (sleeping sickness). The collapsing FSGS variant is particularly associated with APOL1. These variants are also relevant in transplantation – donor kidneys with two APOL1 risk alleles have shorter graft survival.

Reference: Kopp et al 2011 – APOL1 and Kidney Disease; KDIGO 2021 – GN