Clinical implications of apolipoprotein L1 testing in patients with focal segmental glomerulosclerosis: a review of diagnostic and prognostic implications
Introduction:
Focal segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome, contributing to 40% of adult and 20% of pediatric cases globally. Apolipoprotein L1 (APOL1) genetic variants, particularly G1 and G2 alleles, play a pivotal role in FSGS pathogenesis, particularly among African-Americans, where 30–40% carry these risk alleles. These variants impair APOL1 function, causing podocyte injury, proteinuria, and progressive kidney damage. Secondary triggers like infections exacerbate susceptibility. Advances in gene-editing technologies, including CRISPR, offer hope for targeted therapies in FSGS management.
Objectives:
This review explores the link between APOL1 variants and FSGS pathogenesis, focusing on their role in podocyte injury and assessing the utility of APOL1 genetic testing in diagnosis and treatment strategies.
Methodology:
A systematic literature review was conducted using Medline, PubMed, Google Scholar, and PsychINFO up to April 2024. Of 331 identified articles, 29 relevant studies were analyzed, emphasizing APOL1 variants’ role in FSGS and implications for genetic testing.
Results:
About 13% of African-Americans carry APOL1 risk alleles, with 30% having at least one allele. Two risk alleles increase lifetime FSGS risk to 4% and ESKD risk to 7–8%. APOL1-associated kidney damage primarily affects podocytes, accelerating glomerulosclerosis. Emerging treatments, such as inaxaplin, reduced proteinuria by 47%, with 40% achieving remission in FSGS cases linked to APOL1.
