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

Rachel K.Y. Hung; Elizabeth Binns-Roemer; John W. Booth; Rachel Hilton; Mark Harber; Beatriz Santana-Suarez; Lucy Campbell; Julie Fox; Andrew Ustianowski; Catherine Cosgrove; James E. Burns; Amanda Clarke; David A. Price; David Chadwick; Denis Onyango; Lisa Hamzah; Kate Bramham; 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; Robert J. Stocker; Pauline Lambert; GEN-AFRICA Study Group

doi:10.1016/j.ekir.2022.01.1054

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

Rachel K.Y. Hung^*, Elizabeth Binns-Roemer, John W. Booth, Rachel Hilton, Mark Harber, Beatriz Santana-Suarez, Lucy Campbell, Julie Fox, Andrew Ustianowski, Catherine Cosgrove, James E. Burns, Amanda Clarke, David A. Price, David Chadwick, Denis Onyango, Lisa Hamzah, Kate Bramham, Caroline A. Sabin, Cheryl A. Winkler, Frank A. PostJohn 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, Robert J. Stocker, Pauline Lambert, GEN-AFRICA Study Group

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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.

Original language	English
Pages (from-to)	786-796
Number of pages	11
Journal	Kidney International Reports
Volume	7
Issue number	4
DOIs	https://doi.org/10.1016/j.ekir.2022.01.1054
Publication status	Published - Apr 2022

Keywords

Africa
APOL1
diaspora
HIV
HIVAN
kidney

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Hung, R. K. Y., Binns-Roemer, E., Booth, J. W., Hilton, R., Harber, M., Santana-Suarez, B., Campbell, L., Fox, J., Ustianowski, A., Cosgrove, C., Burns, J. E., Clarke, A., Price, D. A., Chadwick, D., Onyango, D., Hamzah, L., Bramham, K., Sabin, C. A., Winkler, C. A., ... GEN-AFRICA Study Group (2022). Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV. Kidney International Reports, 7(4), 786-796. https://doi.org/10.1016/j.ekir.2022.01.1054

@article{b405feb7c604464a90a767b4814fa5e5,

title = "Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV",

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.",

keywords = "Africa, APOL1, diaspora, HIV, HIVAN, kidney",

author = "Hung, {Rachel K.Y.} and Elizabeth Binns-Roemer and Booth, {John W.} and Rachel Hilton and Mark Harber and Beatriz Santana-Suarez and Lucy Campbell and Julie Fox and Andrew Ustianowski and Catherine Cosgrove and Burns, {James E.} and Amanda Clarke and Price, {David A.} and David Chadwick and Denis Onyango and Lisa Hamzah and Kate Bramham 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 Stocker, {Robert J.} 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. 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: {\textcopyright} 2022 International Society of Nephrology",

year = "2022",

month = apr,

doi = "10.1016/j.ekir.2022.01.1054",

language = "English",

volume = "7",

pages = "786--796",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier Inc.",

number = "4",

}

Hung, RKY, Binns-Roemer, E, Booth, JW, Hilton, R, Harber, M, Santana-Suarez, B, Campbell, L, Fox, J, Ustianowski, A, Cosgrove, C, Burns, JE, Clarke, A, Price, DA, Chadwick, D, Onyango, D, Hamzah, L, Bramham, K, 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, Stocker, RJ, Lambert, P & GEN-AFRICA Study Group 2022, 'Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV', Kidney International Reports, vol. 7, no. 4, pp. 786-796. https://doi.org/10.1016/j.ekir.2022.01.1054

TY - JOUR

T1 - Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV

AU - Hung, Rachel K.Y.

AU - Binns-Roemer, Elizabeth

AU - Booth, John W.

AU - Hilton, Rachel

AU - Harber, Mark

AU - Santana-Suarez, Beatriz

AU - Campbell, Lucy

AU - Fox, Julie

AU - Ustianowski, Andrew

AU - Cosgrove, Catherine

AU - Burns, James E.

AU - Clarke, Amanda

AU - Price, David A.

AU - Chadwick, David

AU - Onyango, Denis

AU - Hamzah, Lisa

AU - Bramham, Kate

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 - Stocker, Robert J.

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. 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

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

KW - Africa

KW - APOL1

KW - diaspora

KW - HIV

KW - HIVAN

KW - kidney

UR - http://www.scopus.com/inward/record.url?scp=85125543888&partnerID=8YFLogxK

UR - https://pubmed.ncbi.nlm.nih.gov/35497797

U2 - 10.1016/j.ekir.2022.01.1054

DO - 10.1016/j.ekir.2022.01.1054

M3 - Article

C2 - 35497797

AN - SCOPUS:85125543888

SN - 2468-0249

VL - 7

SP - 786

EP - 796

JO - Kidney International Reports

JF - Kidney International Reports

IS - 4

ER -

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

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