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

Research output: Contribution to journalArticlepeer-review

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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