Apolipoprotein L1 gene variants and kidney disease in patients with HIV: a systematic review and meta-analysis.

Background: The risk of various types of kidney disease is significantly increased in the presence of APOL1 high-risk genotype (carriage of two risk alleles), particularly HIV-associated nephropathy (HIVAN). However, there are discrepancies in the existing evidence about the level of association between APOL1 high-risk genotype and the risk of kidney diseases in people living with HIV (PLWHIV).

Methods: This systematic review and meta-analysis was conducted to assess the relationship between the APOL1 genotypes and kidney disease in the HIV population. An a priori protocol registered on PROSPERO (ID: CRD42021253877), was followed by a systematic search of five electronic databases. Database-specific search terms were used to identify observational studies that evaluated the outcomes chosen in the review, based on a set of prespecified eligibility criteria. Using a random effect model, the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were pooled for the meta-analysis.

Results: After screening 4418 citations, 14 articles comprising 11,069 participants were included in this review. The risk of chronic kidney disease (CKD) in the HIV positive population was significantly increased in the presence of two APOL1 risk alleles (OR 4.65 [95% CI 3.51-6.15]). Also, a significant association was observed between the carriage of two risk APOL1 variants and proteinuria (OR 2.58 [95% CI 2.05-3.25]), HIVAN (OR 16.67 [95% CI 10.22-27.19]), and progression to end-stage kidney disease (ESKD) hazard ratio: 1.79 (95% CI 1.20-2.66).

Conclusion: This review highlights a strong association between the presence of two risk APOL1 variants and an increased risk of kidney disease in PLWHIV, and provides a more precise estimate of the effect size, with smaller 95% CIs for CKD, HIVAN, and progression to ESKD.