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

doi:10.1016/j.ekir.2021.12.007

. 2021 Dec 13;7(3):465-473.

doi: 10.1016/j.ekir.2021.12.007. eCollection 2022 Mar.

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

Rachel K Y Hung¹, Elizabeth Binns-Roemer², John W Booth³, Rachel Hilton⁴, Julie Fox^{1

4}, Fiona Burns⁵, Mark Harber⁵, Andrew Ustianowski⁶, Lisa Hamzah⁷, James E Burns^{8

9}, Amanda Clarke^{10

11}, David A Price¹², Stephen Kegg¹³, Denis Onyango¹⁴, Beatriz Santana-Suarez¹, Lucy Campbell¹, Kate Bramham^{1

15}, Claire C Sharpe^{1

15}, Caroline A Sabin⁸, Cheryl A Winkler², Frank A Post^{1

15}; GEN-AFRICA Study Group

Collaborators, Affiliations

Collaborators

GEN-AFRICA Study Group:
John Booth, Anele Waters, James Hand, Chris Clarke, Sarah Murphy, Maurice Murphy, Marion Campbell, Amanda Clarke, 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, Rachel Hilton, Julie Fox, May Rabuya, Lisa Hamzah, Deborah Jordan, Teresa Solano, Hiromi Uzu, Karen Williams, Julianne Lwanga, Linda Ekaette Reid-Amoruso, Hannah Gamlen, Robert J Stocker, Fiona Ryan, Anele Waters, Karina Mahiouz, Tess Cheetham, Claire Williams, Achyuta Nori, Caroline Thomas, Sivaraj Venkateshwaran, Jessica Doctor, Andrea Berlanga, Frank Post, Beatriz Santana-Suarez, Leigh McQueen, Priya Bhagwandin, Lucy Campbell, Bee Barbini, Emily Wandolo, Tim Appleby, Deborah Jordan, Lois Driver, Sophy Parr, Hongbo Deng, Julie Barber, Andrew Crowe, Chris Taylor, Mary Poulton, Vida Boateng, Marie-Pierre Klein, Caitlin O'Brien, Samuel Ohene-Adomako, Christian Buckingham, Daniel Trotman, Killian Quinn, Kate Flanagan, Verity Sullivan, Holly Middleditch, Itty Samuel, Elizabeth Hamlyn, Candice McDonald, Ana Canoso, Emeka Agbasi, Maria Liskova, Sarah Barber, Amanda Samarawickrama, Zoe Ottaway, Claire Norcross, Amelia Oliveira, Kate Bramham, Jane Minton, Gary Lamont, Ruby Cross, Gaushiya Saiyad, Shadia Ahmed, Rebecca Ashworth, Nicola Window, J Murira, Khine Phyu, Andrew Ustianowski, Gabriella Lindergard, Jonathan Shaw, Sarah Holland, Claire Fox, Jan Flaherty, Margaret-Anne Bevan, Valerie George, David Chadwick, Marie Branch, Pauline Lambert, Adele Craggs, Sarah Pett, Hinal Lukha, Nina Vora, Marzia Fiorino, Maria Muller Nunez, Deirdre Sally, James E Burns, Erica Pool, Rebecca Matthews, David Ashley Price, Tara Stothard, Bijal Patel, Ian McVittie, Ciara Kennedy, Uli Shwab, Brendan Payne, Sarah Duncan, Jill Dixon, Mathias Schmid, Adam Evans, Christopher Duncan, Ewan Hunter, Yusri Taha, Natasha Astill, Cheryl Winkler, Elizabeth Binns-Roemer, Victor David, Jonathan Ainsworth, Rachel Vincent, Stephen Kegg, Chloe Saad, Sarah Skinner, Hocine Azzoug, Judith Russell, Tarik Moussaoui, Celia Richardson, Emily Mabonga, Donna Ward, J Francoise, W Larbi, Sue Mitchell, A Manning, V Russell, Fiona Burns, Mark Harber, Nnenna Ngwu, Jonathan Edwards, Nargis Hemat, Tom Fernandez, Filippo Ferro, Jorge Ferreira, Alice Nightingale, Tasha Oakes-Monger, Darwin Matila, Pedro Nogueira, Victoria Mutagwanya, Catherine Cosgrove, Lisa Hamzah, Catherine Emily Isitt, Helen Webb, Joyce Popoola, Kate Korley, Mark Mencias, Patricia Ribeiro, Rajeshwar Ramkhelawn, Sandra Oliva Lara, Sara Sajijad, Alan Winston, Jeremy Levy, Amber Shaw, Claire Petersen, Kyle Ring, Melanie Rosenvinge, Chloe Saad, Sarah Skinner, Thembi Moyo, Faith Odong, Katherine Gantert, Tina Ibe, Denis Onyango, Caroline Sabin, Teresa Hill

Affiliations

¹ King's College London, London, UK.
² Basic Research Laboratory, Frederick National Laboratory for Cancer Research and the National Cancer Institute, Frederick, Maryland, USA.
³ Barts Health NHS Trust, London, UK.
⁴ Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁵ Royal Free London Hospital NHS Foundation Trust, London, UK.
⁶ Pennine Acute Hospitals NHS Foundation Trust, Manchester, UK.
⁷ St George's Hospital NHS Foundation Trust, London, UK.
⁸ University College London, London, UK.
⁹ Central and North West London NHS Foundation Trust, London, UK.
¹⁰ Brighton and Sussex University Hospital NHS Trust, Brighton, UK.
¹¹ Department of Infectious Disease, Brighton and Sussex Medical School, Brighton, UK.
¹² The Newcastle Upon Tyne Hospitals, Newcastle, UK.
¹³ Lewisham and Greenwich NHS Trust, London, UK.
¹⁴ Africa Advocacy Foundation, London, UK.
¹⁵ King's College Hospital NHS Foundation Trust, London, UK.

PMID: 35257059
PMCID: PMC8897676
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 et al. Kidney Int Rep. 2021.

. 2021 Dec 13;7(3):465-473.

doi: 10.1016/j.ekir.2021.12.007. eCollection 2022 Mar.

Authors

Collaborators

GEN-AFRICA Study Group:
John Booth, Anele Waters, James Hand, Chris Clarke, Sarah Murphy, Maurice Murphy, Marion Campbell, Amanda Clarke, 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, Rachel Hilton, Julie Fox, May Rabuya, Lisa Hamzah, Deborah Jordan, Teresa Solano, Hiromi Uzu, Karen Williams, Julianne Lwanga, Linda Ekaette Reid-Amoruso, Hannah Gamlen, Robert J Stocker, Fiona Ryan, Anele Waters, Karina Mahiouz, Tess Cheetham, Claire Williams, Achyuta Nori, Caroline Thomas, Sivaraj Venkateshwaran, Jessica Doctor, Andrea Berlanga, Frank Post, Beatriz Santana-Suarez, Leigh McQueen, Priya Bhagwandin, Lucy Campbell, Bee Barbini, Emily Wandolo, Tim Appleby, Deborah Jordan, Lois Driver, Sophy Parr, Hongbo Deng, Julie Barber, Andrew Crowe, Chris Taylor, Mary Poulton, Vida Boateng, Marie-Pierre Klein, Caitlin O'Brien, Samuel Ohene-Adomako, Christian Buckingham, Daniel Trotman, Killian Quinn, Kate Flanagan, Verity Sullivan, Holly Middleditch, Itty Samuel, Elizabeth Hamlyn, Candice McDonald, Ana Canoso, Emeka Agbasi, Maria Liskova, Sarah Barber, Amanda Samarawickrama, Zoe Ottaway, Claire Norcross, Amelia Oliveira, Kate Bramham, Jane Minton, Gary Lamont, Ruby Cross, Gaushiya Saiyad, Shadia Ahmed, Rebecca Ashworth, Nicola Window, J Murira, Khine Phyu, Andrew Ustianowski, Gabriella Lindergard, Jonathan Shaw, Sarah Holland, Claire Fox, Jan Flaherty, Margaret-Anne Bevan, Valerie George, David Chadwick, Marie Branch, Pauline Lambert, Adele Craggs, Sarah Pett, Hinal Lukha, Nina Vora, Marzia Fiorino, Maria Muller Nunez, Deirdre Sally, James E Burns, Erica Pool, Rebecca Matthews, David Ashley Price, Tara Stothard, Bijal Patel, Ian McVittie, Ciara Kennedy, Uli Shwab, Brendan Payne, Sarah Duncan, Jill Dixon, Mathias Schmid, Adam Evans, Christopher Duncan, Ewan Hunter, Yusri Taha, Natasha Astill, Cheryl Winkler, Elizabeth Binns-Roemer, Victor David, Jonathan Ainsworth, Rachel Vincent, Stephen Kegg, Chloe Saad, Sarah Skinner, Hocine Azzoug, Judith Russell, Tarik Moussaoui, Celia Richardson, Emily Mabonga, Donna Ward, J Francoise, W Larbi, Sue Mitchell, A Manning, V Russell, Fiona Burns, Mark Harber, Nnenna Ngwu, Jonathan Edwards, Nargis Hemat, Tom Fernandez, Filippo Ferro, Jorge Ferreira, Alice Nightingale, Tasha Oakes-Monger, Darwin Matila, Pedro Nogueira, Victoria Mutagwanya, Catherine Cosgrove, Lisa Hamzah, Catherine Emily Isitt, Helen Webb, Joyce Popoola, Kate Korley, Mark Mencias, Patricia Ribeiro, Rajeshwar Ramkhelawn, Sandra Oliva Lara, Sara Sajijad, Alan Winston, Jeremy Levy, Amber Shaw, Claire Petersen, Kyle Ring, Melanie Rosenvinge, Chloe Saad, Sarah Skinner, Thembi Moyo, Faith Odong, Katherine Gantert, Tina Ibe, Denis Onyango, Caroline Sabin, Teresa Hill

Affiliations

¹ King's College London, London, UK.
² Basic Research Laboratory, Frederick National Laboratory for Cancer Research and the National Cancer Institute, Frederick, Maryland, USA.
³ Barts Health NHS Trust, London, UK.
⁴ Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁵ Royal Free London Hospital NHS Foundation Trust, London, UK.
⁶ Pennine Acute Hospitals NHS Foundation Trust, Manchester, UK.
⁷ St George's Hospital NHS Foundation Trust, London, UK.
⁸ University College London, London, UK.
⁹ Central and North West London NHS Foundation Trust, London, UK.
¹⁰ Brighton and Sussex University Hospital NHS Trust, Brighton, UK.
¹¹ Department of Infectious Disease, Brighton and Sussex Medical School, Brighton, UK.
¹² The Newcastle Upon Tyne Hospitals, Newcastle, UK.
¹³ Lewisham and Greenwich NHS Trust, London, UK.
¹⁴ Africa Advocacy Foundation, London, UK.
¹⁵ King's College Hospital NHS Foundation Trust, London, UK.

PMID: 35257059
PMCID: PMC8897676
DOI: 10.1016/j.ekir.2021.12.007

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: APOL1; Africa; HIV; SCT; kidney; sickle cell trait.

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Figures

**Figure 1**
(a) Proportion of eGFR of all study participants stratified by SCT and by APOL1 status; (b) Proportion of study participants with sickle cell trait in each eGFR stratum. eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; SCT, sickle cell trait.

See this image and copyright information in PMC

Comment in

APOL1, Sickle Cell Trait, and Glutathione S-Transferase 1-More Complicated Than It Seems.
Kruzel-Davila E, Madhavan SM. Kruzel-Davila E, et al. Kidney Int Rep. 2022 Jan 4;7(3):368-370. doi: 10.1016/j.ekir.2021.12.036. eCollection 2022 Mar. Kidney Int Rep. 2022. PMID: 35258513 Free PMC article. No abstract available.

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A Scoping Review on Sex and Gender Differences in the Adverse Health Outcomes of Individuals with Sickle Cell Trait.
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APOL1, Sickle Cell Trait, and Glutathione S-Transferase 1-More Complicated Than It Seems.
Kruzel-Davila E, Madhavan SM. Kruzel-Davila E, et al. Kidney Int Rep. 2022 Jan 4;7(3):368-370. doi: 10.1016/j.ekir.2021.12.036. eCollection 2022 Mar. Kidney Int Rep. 2022. PMID: 35258513 Free PMC article. No abstract available.
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References

1. George J.A., Brandenburg J.T., Fabian J., et al. Kidney damage and associated risk factors in rural and urban sub-Saharan Africa (AWI-Gen): a cross-sectional population study. Lancet Glob Health. 2019;7:e1632–e1643. doi: 10.1016/S2214-109X(19)30443-7. - DOI - PMC - PubMed
1. Kaze A.D., Ilori T., Jaar B.G., Echouffo-Tcheugui J.B. Burden of chronic kidney disease on the African continent: a systematic review and meta-analysis. BMC Nephrol. 2018;19:125. doi: 10.1186/s12882-018-0930-5. - DOI - PMC - PubMed
1. Booth J.W., Hamzah L., Jose S., et al. Clinical characteristics and outcomes of HIV-associated immune complex kidney disease. Nephrol Dial Transpl. 2016;31:2099–2107. doi: 10.1093/ndt/gfv436. - DOI - PubMed
1. Atta M.G., Estrella M.M., Kuperman M., et al. HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics. Kidney Int. 2012;82:338–343. doi: 10.1038/ki.2012.111. - DOI - PMC - PubMed
1. Wearne N., Swanepoel C.R., Boulle A., Duffield M.S., Rayner B.L. The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations. Nephrol Dial Transplant. 2012;27:4109–4118. doi: 10.1093/ndt/gfr702. - DOI - PubMed

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[1] George J.A., Brandenburg J.T., Fabian J., et al. Kidney damage and associated risk factors in rural and urban sub-Saharan Africa (AWI-Gen): a cross-sectional population study. Lancet Glob Health. 2019;7:e1632–e1643. doi: 10.1016/S2214-109X(19)30443-7. - DOI - PMC - PubMed

[2] George J.A., Brandenburg J.T., Fabian J., et al. Kidney damage and associated risk factors in rural and urban sub-Saharan Africa (AWI-Gen): a cross-sectional population study. Lancet Glob Health. 2019;7:e1632–e1643. doi: 10.1016/S2214-109X(19)30443-7. - DOI - PMC - PubMed

[3] Kaze A.D., Ilori T., Jaar B.G., Echouffo-Tcheugui J.B. Burden of chronic kidney disease on the African continent: a systematic review and meta-analysis. BMC Nephrol. 2018;19:125. doi: 10.1186/s12882-018-0930-5. - DOI - PMC - PubMed

[4] Kaze A.D., Ilori T., Jaar B.G., Echouffo-Tcheugui J.B. Burden of chronic kidney disease on the African continent: a systematic review and meta-analysis. BMC Nephrol. 2018;19:125. doi: 10.1186/s12882-018-0930-5. - DOI - PMC - PubMed

[5] Booth J.W., Hamzah L., Jose S., et al. Clinical characteristics and outcomes of HIV-associated immune complex kidney disease. Nephrol Dial Transpl. 2016;31:2099–2107. doi: 10.1093/ndt/gfv436. - DOI - PubMed

[6] Booth J.W., Hamzah L., Jose S., et al. Clinical characteristics and outcomes of HIV-associated immune complex kidney disease. Nephrol Dial Transpl. 2016;31:2099–2107. doi: 10.1093/ndt/gfv436. - DOI - PubMed

[7] Atta M.G., Estrella M.M., Kuperman M., et al. HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics. Kidney Int. 2012;82:338–343. doi: 10.1038/ki.2012.111. - DOI - PMC - PubMed

[8] Atta M.G., Estrella M.M., Kuperman M., et al. HIV-associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and pathological characteristics. Kidney Int. 2012;82:338–343. doi: 10.1038/ki.2012.111. - DOI - PMC - PubMed

[9] Wearne N., Swanepoel C.R., Boulle A., Duffield M.S., Rayner B.L. The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations. Nephrol Dial Transplant. 2012;27:4109–4118. doi: 10.1093/ndt/gfr702. - DOI - PubMed

[10] Wearne N., Swanepoel C.R., Boulle A., Duffield M.S., Rayner B.L. The spectrum of renal histologies seen in HIV with outcomes, prognostic indicators and clinical correlations. Nephrol Dial Transplant. 2012;27:4109–4118. doi: 10.1093/ndt/gfr702. - DOI - PubMed

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

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

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