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

Journal
Frontiers in medicine (Q1)
Published
19 August 2026
Study design
Systematic review of cohort studies
Evidence level
Level 2, Moderate (CEBM 2a)
Authors
Silvia E Aldana-Pérez, Alex Dominguez-Vargas, Gustavo Aroca-Martinez, Ana Moreno-Woo, Luis Fang, Gloria Garavito De Egea, et al.
PMID
42688565
DOI
10.3389/fmed.2026.1903888

Why clinicians should know about it

  • Picked for Rheumatology (top studies of the week, 6 September 2026): APOL1 risk genotypes increase lupus nephritis ESRD odds

Abstract

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).

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.