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Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV

Research output: Contribution to journalArticlepeer-review

GEN-AFRICA study group, Frank A. Post

Original languageEnglish
Pages (from-to)786-796
Number of pages11
JournalKidney International Reports
Volume7
Issue number4
Early online date25 Jan 2022
DOIs
Accepted/In press17 Jan 2022
E-pub ahead of print25 Jan 2022
Published1 Apr 2022

Bibliographical note

Funding Information: The authors would like to thank the study participants and all members of the GEN-AFRICA study group (Appendix). This study was supported by the Medical Research Council (UK) Confidence in Concept scheme (MC_PC_17164), and in part by the National Institutes of Health and the National Cancer Institute Intramural Research Program (CAW) and under contract HHSN26120080001E. The content of this publication does not necessarily reflect the view or policy of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the government. The study was designed by CAW and FAP. LH, JF, JB, AC, RV, RJ, DP, MH, RH, JB, and FAP were site principal investigators and coordinated recruitment and data collection at their sites. BSS, EBR, and LC assisted with logistic and governance aspects. JB preformed a review of all kidney biopsy reports with assistance from Dr. Catherine Horsfield. RH and FAP performed the analyses with input from CAS and CAW. RH, KB, CAS, CAW, and FAP interpreted the findings. RH wrote the first draft of the manuscript with input from CAS, CAW, and FAP. RH and FP verified the underlying data. All authors revised and approved the final version of the manuscript. Publisher Copyright: © 2022 International Society of Nephrology

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King's Authors

Abstract

Introduction: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. Methods: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR <60 ml/min per 1.73 m2), albuminuria (albumin-to-creatinine ratio [ACR] >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. Results: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. Conclusion: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.

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