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Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

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GEN-AFRICA study group, Rachel K.Y. Hung, Elizabeth Binns-Roemer, John W. Booth, Rachel Hilton, Julie Fox, Fiona Burns, Mark Harber, Andrew Ustianowski, Lisa Hamzah, James E. Burns, Amanda Clarke, David A. Price, Stephen Kegg, Denis Onyango, Beatriz Santana-Suarez, Lucy Campbell, Kate Bramham, Claire C. Sharpe, Caroline A. Sabin & 31 more Cheryl A. Winkler, Frank A. Post, John Booth, Anele Waters, James Hand, Chris Clarke, Sarah Murphy, Maurice Murphy, Marion Campbell, Celia Richardson, Alyson Knott, Gemma Weir, Rebecca Cleig, Helena Soviarova, Lisa Barbour, Tanya Adams, Vicky Kennard, Vittorio Trevitt, Rachael Jones, Jeremy Levy, Alexandra Schoolmeester, Serah Duro, May Rabuya, Deborah Jordan, Teresa Solano, Frank A. Post, Mary Poulton, Jan Flaherty, Bijal Patel, A. Manning, Joyce Popoola

Original languageEnglish
Pages (from-to)465-473
Number of pages9
JournalKidney International Reports
Volume7
Issue number3
Early online date13 Dec 2021
DOIs
E-pub ahead of print13 Dec 2021
Published1 Mar 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. 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. JWB, RH, JF, FB, MH, AU, LH, JEB, AC, DAP, SK, and FAP were site principal investigators and/or coordinated recruitment and data collection at their sites. EBR performed the genotyping in CAW's laboratory. BSS and LC assisted with logistic and governance aspects, and DO provided community perspective. RKYH and FAP performed the analyses with input from CAS and CAW. RKYH, JWB, KB, CS, KB, CAS, CAW, and FAP interpreted the findings. FAP and RKYH wrote the first draft of the manuscript with input from RH, CS, KB, CAS, CAW, and FAP. All authors revised and approved the final version of the manuscript. Publisher Copyright: © 2021 International Society of Nephrology

King's Authors

Abstract

Introduction: Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK. Methods: The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Secondary outcomes were eGFR <90 ml/min per 1.73 m2, end-stage kidney disease (ESKD; eGFR <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant), proteinuria (protein-to-creatinine ratio >50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes. Results: A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 [95% CI 1.14–2.32]), eGFR <90 ml/min per 1.73 m2 (1.50 [1.14–1.97]), and albuminuria (1.50 [1.09–2.05]). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes. Conclusion: Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes.

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