The association between APOL1 risk alleles and longitudinal kidney function differs by HIV viral suppression status

Michelle M. Estrella*, Man Li, Adrienne Tin, Alison G. Abraham, Michael G. Shlipak, Sudhir Penugonda, Shehnaz K. Hussain, Frank J. Palella, Steven M. Wolinsky, Jeremy J. Martinson, Rulan S. Parekh, W. H.Linda Kao

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background.Existing data suggest that human immunodeficiency virus (HIV)-infected African Americans carrying 2 copies of the APOL1 risk alleles have greater risk of kidney disease than noncarriers. We sought to determine whether HIV RNA suppression mitigates APOL1-related kidney function decline among African Americans enrolled in the Multicenter AIDS Cohort Study. Methods.We genotyped HIV-infected men for the G1 and G2 risk alleles and ancestry informative markers. Mixed-effects models were used to estimate the annual rate of estimated glomerular filtration rate (eGFR) decline, comparing men carrying 2 (high-risk) vs 0-1 risk allele (low-risk). Effect modification by HIV suppression status (defined as HIV type 1 RNA level <400 copies/mL for >90% of follow-up time) was evaluated using interaction terms and stratified analyses. Results.Of the 333 African American men included in this study, 54 (16%) carried the APOL1 high-risk genotype. Among HIV-infected men with unsuppressed viral loads, those with the high-risk genotype had a 2.42 mL/minute/1.73 m2 (95% confidence interval [CI], -3.52 to -1.32) faster annual eGFR decline than men with the low-risk genotype. This association was independent of age, comorbid conditions, baseline eGFR, ancestry, and HIV-related factors. In contrast, the rate of decline was similar by APOL1 genotype among men with sustained viral suppression (-0.16 mL/minute/1.73 m2/year; 95% CI, -.59 to. 27; P for interaction <.001). Conclusions.Unsuppressed HIV-infected African Americans with the APOL1 high-risk genotype experience an accelerated rate of kidney function decline; HIV suppression with antiretroviral therapy may reduce these deleterious renal effects.

Original languageEnglish (US)
Pages (from-to)646-652
Number of pages7
JournalClinical Infectious Diseases
Volume60
Issue number4
DOIs
StatePublished - Feb 15 2015

Keywords

  • HIV
  • antiretroviral therapy
  • genetic
  • kidney disease

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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