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

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; 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; Hiromi Uzu; Karen Williams; Julianne Lwanga; Linda Ekaette Reid-Amoruso; Hannah Gamlen; Pauline Lambert; GEN-AFRICA Study Group

doi:10.1016/j.ekir.2021.12.007

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

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, Cheryl A. WinklerFrank 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, Hiromi Uzu, Karen Williams, Julianne Lwanga, Linda Ekaette Reid-Amoruso, Hannah Gamlen, Pauline Lambert, GEN-AFRICA Study Group

^*Corresponding author for this work

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Research output: Contribution to journal › Article › Research › peer-review

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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.

Original language	English
Pages (from-to)	465-473
Number of pages	9
Journal	Kidney International Reports
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.ekir.2021.12.007
Publication status	Published - Mar 2022

Keywords

Africa
APOL1
HIV
kidney
SCT
sickle cell trait

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Hung, R. K. Y., Binns-Roemer, E., Booth, J. W., Hilton, R., Fox, J., Burns, F., Harber, M., Ustianowski, A., Hamzah, L., Burns, J. E., Clarke, A., Price, D. A., Kegg, S., Onyango, D., Santana-Suarez, B., Campbell, L., Bramham, K., Sharpe, C. C., Sabin, C. A., ... GEN-AFRICA Study Group (2022). Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV. Kidney International Reports, 7(3), 465-473. https://doi.org/10.1016/j.ekir.2021.12.007

@article{47ebe5df1c624b4295f529ad0fd2bbfb,

title = "Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV",

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.",

keywords = "Africa, APOL1, HIV, kidney, SCT, sickle cell trait",

author = "Hung, {Rachel K.Y.} and Elizabeth Binns-Roemer and Booth, {John W.} and Rachel Hilton and Julie Fox and Fiona Burns and Mark Harber and Andrew Ustianowski and Lisa Hamzah and Burns, {James E.} and Amanda Clarke and Price, {David A.} and Stephen Kegg and Denis Onyango and Beatriz Santana-Suarez and Lucy Campbell and Kate Bramham and Sharpe, {Claire C.} and Sabin, {Caroline A.} and Winkler, {Cheryl A.} and Post, {Frank A.} and John Booth and Anele Waters and James Hand and Chris Clarke and Sarah Murphy and Maurice Murphy and Marion Campbell and Celia Richardson and Alyson Knott and Gemma Weir and Rebecca Cleig and Helena Soviarova and Lisa Barbour and Tanya Adams and Vicky Kennard and Vittorio Trevitt and Rachael Jones and Jeremy Levy and Alexandra Schoolmeester and Serah Duro and May Rabuya and Deborah Jordan and Teresa Solano and Hiromi Uzu and Karen Williams and Julianne Lwanga and Reid-Amoruso, {Linda Ekaette} and Hannah Gamlen and Pauline Lambert and {GEN-AFRICA Study Group}",

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: {\textcopyright} 2021 International Society of Nephrology",

year = "2022",

month = mar,

doi = "10.1016/j.ekir.2021.12.007",

language = "English",

volume = "7",

pages = "465--473",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier Inc.",

number = "3",

}

Hung, RKY, Binns-Roemer, E, Booth, JW, Hilton, R, Fox, J, Burns, F, Harber, M, Ustianowski, A, Hamzah, L, Burns, JE, Clarke, A, Price, DA, Kegg, S, Onyango, D, Santana-Suarez, B, Campbell, L, Bramham, K, Sharpe, CC, Sabin, CA, Winkler, CA, Post, FA, Booth, J, Waters, A, Hand, J, Clarke, C, Murphy, S, Murphy, M, Campbell, M, Richardson, C, Knott, A, Weir, G, Cleig, R, Soviarova, H, Barbour, L, Adams, T, Kennard, V, Trevitt, V, Jones, R, Levy, J, Schoolmeester, A, Duro, S, Rabuya, M, Jordan, D, Solano, T, Uzu, H, Williams, K, Lwanga, J, Reid-Amoruso, LE, Gamlen, H, Lambert, P & GEN-AFRICA Study Group 2022, 'Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV', Kidney International Reports, vol. 7, no. 3, pp. 465-473. https://doi.org/10.1016/j.ekir.2021.12.007

TY - JOUR

T1 - Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

AU - Hung, Rachel K.Y.

AU - Binns-Roemer, Elizabeth

AU - Booth, John W.

AU - Hilton, Rachel

AU - Fox, Julie

AU - Burns, Fiona

AU - Harber, Mark

AU - Ustianowski, Andrew

AU - Hamzah, Lisa

AU - Burns, James E.

AU - Clarke, Amanda

AU - Price, David A.

AU - Kegg, Stephen

AU - Onyango, Denis

AU - Santana-Suarez, Beatriz

AU - Campbell, Lucy

AU - Bramham, Kate

AU - Sharpe, Claire C.

AU - Sabin, Caroline A.

AU - Winkler, Cheryl A.

AU - Post, Frank A.

AU - Booth, John

AU - Waters, Anele

AU - Hand, James

AU - Clarke, Chris

AU - Murphy, Sarah

AU - Murphy, Maurice

AU - Campbell, Marion

AU - Richardson, Celia

AU - Knott, Alyson

AU - Weir, Gemma

AU - Cleig, Rebecca

AU - Soviarova, Helena

AU - Barbour, Lisa

AU - Adams, Tanya

AU - Kennard, Vicky

AU - Trevitt, Vittorio

AU - Jones, Rachael

AU - Levy, Jeremy

AU - Schoolmeester, Alexandra

AU - Duro, Serah

AU - Rabuya, May

AU - Jordan, Deborah

AU - Solano, Teresa

AU - Uzu, Hiromi

AU - Williams, Karen

AU - Lwanga, Julianne

AU - Reid-Amoruso, Linda Ekaette

AU - Gamlen, Hannah

AU - Lambert, Pauline

AU - GEN-AFRICA Study Group

N1 - 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

PY - 2022/3

Y1 - 2022/3

N2 - 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.

AB - 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.

KW - Africa

KW - APOL1

KW - HIV

KW - kidney

KW - SCT

KW - sickle cell trait

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UR - https://pubmed.ncbi.nlm.nih.gov/35257059

U2 - 10.1016/j.ekir.2021.12.007

DO - 10.1016/j.ekir.2021.12.007

M3 - Article

C2 - 35257059

AN - SCOPUS:85122618881

SN - 2468-0249

VL - 7

SP - 465

EP - 473

JO - Kidney International Reports

JF - Kidney International Reports

IS - 3

ER -

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

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