Apolipoprotein L1 risk genotypes and odds of lupus nephritis-associated kidney failure in systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by a prominent interferon signature that upregulates apolipoprotein L1 (APOL1) expression. High-risk APOL1 genotypes have been associated with end-stage renal disease (ESRD) as a complication of lupus nephritis (LN); however, the strength and consistency of this association remain heterogeneous across studies. METHODS: We conducted a systematic review and meta-analysis of observational studies to evaluate the association between APOL1 genotypes and the odds of LN-associated kidney failure among patients with SLE. A systematic search of PubMed, Scopus, and Web of Science identified eligible observational studies, and pooled odds ratios with 95% confidence intervals were estimated using random-effects models. Between-study heterogeneity and publication bias were assessed using standard methods. RESULTS: Four observational studies comprising a total of 1,885 patients of African ancestry were included. Of these, 321 carried high-risk APOL1 genotypes and 1,564 carried low-risk genotypes. High-risk APOL1 genotypes were associated with significantly increased odds of LN-associated ESRD compared with low-risk genotypes (OR 2.66; 95% CI 1.63-4.32; p = 0.008), with low heterogeneity (I 2 = 9.8%). Chronic kidney disease outcomes were reported heterogeneously and were summarized descriptively. CONCLUSION: High-risk APOL1 genotypes are associated with significantly increased pooled odds of LN-associated ESRD among patients with SLE. These findings demonstrate that APOL1 is a clinically relevant genetic modifier of renal prognosis, supporting its potential role as a tool for risk stratification and precision medicine approaches in LN. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024587943, identifier PROSPERO (CRD42024587943).