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. 2022 Jan 25;7(4):786-796.
doi: 10.1016/j.ekir.2022.01.1054. eCollection 2022 Apr.

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

Rachel K Y Hung  1 , Elizabeth Binns-Roemer  2 , John W Booth  3 , Rachel Hilton  4 , Mark Harber  5 , Beatriz Santana-Suarez  1 , Lucy Campbell  1 , Julie Fox  1   4 , Andrew Ustianowski  6 , Catherine Cosgrove  7 , James E Burns  8   9 , Amanda Clarke  10   11 , David A Price  12 , David Chadwick  13 , Denis Onyango  14 , Lisa Hamzah  7 , Kate Bramham  1   15 , Caroline A Sabin  8 , Cheryl A Winkler  2 , Frank A Post  1   15 ; GEN-AFRICA Study Group
Collaborators, Affiliations

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

Rachel K Y Hung et al. Kidney Int Rep. .

Erratum in

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: APOL1; Africa; HIV; HIVAN; diaspora; kidney.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Distribution of APOL1 alleles by region of African ancestry, in (a) all participants and (b) those with ESKD. East, South, Central, and West refer to regions within sub-Saharan Africa; ESKD includes participants with eGFR. Numerical data are shown in Supplementary Table S7. eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.
Figure 2
Figure 2
Kidney function, kidney pathology and APOL1 genotype. Distribution of (a) eGFR, (b) uPCR, (c) uACR, and (d) cases of HIVAN/FSGS by APOL1 status, and prevalence of APOL1 high-risk genotypes by (e) eGFR, (f) PCR, (g) ACR categories, and (h) HIVAN/FSGS status. eGFR, estimated glomerular filtration rate; FSGS, focal and segmental glomerulosclerosis; HIVAN, HIV-associated nephropathy; RRT, renal replacement therapy; uACR, urine albumin-to-creatinine ratio; uPCR, urine protein-to-creatinine ratio.
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References

    1. US Census Bureau QuickFacts: United States. US Census Bureau. Accessed May 12, 2021. https://www.census.gov/quickfacts/fact/table/US/PST045219
    1. Levey A.S., Coresh J., Balk E., et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification [published correction appears in Ann Intern Med. 2003 Oct 7;139(7):605] Ann Intern Med. 2003;139:137–147. doi: 10.7326/0003-4819-139-2-200307150-00013. - DOI - PubMed
    1. Lightstone L. Preventing renal disease: the ethnic challenge in the United Kingdom. Kidney Int Suppl. 2003;63:S135–S138. doi: 10.1046/j.1523-1755.63.s83.29.x. - DOI - PubMed
    1. Wilkinson E., Brettle A., Waqar M., Randhawa G. Inequalities and outcomes: end stage kidney disease in ethnic minorities. BMC Nephrol. 2019;20:234. doi: 10.1186/s12882-019-1410-2. - DOI - PMC - PubMed
    1. Grams M.E., Rebholz C.M., Chen Y., et al. Race, APOL1 risk, and EGFR decline in the general population. J Am Soc Nephrol. 2016;27:2842–2850. doi: 10.1681/ASN.2015070763. - DOI - PMC - PubMed