Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

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Abstract

BACKGROUND/OBJECTIVES: APOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0–1 risk alleles) and self-reported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study. DESIGN: Observational longitudinal cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study. PARTICIPANTS: Community-dwelling older adults (mean age = 75.8 years; range = 66–90 years). RESULTS: Among 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C–based estimated glomerular filtration rate (eGFRCrCys) below 60 mL/min/1.73 m2 at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05–6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFRCrCys and albuminuria (hazard ratio [HR] = 1.08; 95% CI =.39–2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFRCrCys, and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06–1.81; ESRD: HR = 3.20; 95% CI = 1.16–8.86). CONCLUSION: Among older Black adults, APOL1 high-risk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalJournal of the American Geriatrics Society
Volume69
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • APOL1
  • apolipoprotein L1
  • chronic kidney disease
  • end-stage renal disease
  • mortality

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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