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

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 selfreported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), endstage 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 (eGFR CrCys ) below 60 mL/min/1.73 m 2 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 eGFR CrCys 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, eGFR CrCys , 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 highrisk 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.

Racial and Sex Disparities in Gout Prevalence Among US Adults

“…Another key risk factor, CKD, also attenuated the racial differences for gout and hyperuricemia, particularly in men, even with prior adjustment for documented CKD risk factors, including adiposity, poverty, and DASH adherence . Although the higher prevalence of CKD in Black adults (compared with White adults) has been attributed in part to the APOL1 risk alleles present in African American populations, evidence suggests that racial differences in sociodemographic, lifestyle, and clinical factors play a greater role, with poorer access to health care among Black individuals also contributing …”

“…Another key risk factor, CKD, also attenuated the racial differences for gout and hyperuricemia, particularly in men, even with prior adjustment for documented CKD risk factors, including adiposity, poverty, 56 and DASH adherence. 57 Although the higher prevalence of CKD in Black adults (compared with White adults) has been attributed in part to the APOL1 risk alleles present in African American populations, 58,59 evidence suggests that racial differences in sociodemographic, lifestyle, and clinical factors play a greater role, 60 with poorer access to health care among Black individuals also contributing. 61 Although gout has historically been viewed as a disease of wealthy White men who could afford to overindulge in alcohol and purine-rich foods, the association between socioeconomic status and gout and hyperuricemia has garnered little empirical study and remains unclear.…”

APOL1 Gene Variants and Risk for Cardiovascular Disease

“…APOL1 was positively associated with CKD (odds ratio 1.37, 95% CI 1.08–1.73), but the risk variants were not significantly associated with prevalent CVD (odds ratio 1.02, 95% CI 0.82–1.27) [6]. The Atherosclerosis Risk in Communities (ARIC) Study found a strong association between the HR APOL1 genotype and ESRD but failed to demonstrate any association with incident CVD in 3,676 African American participants [13].…”

Expanding Access to Organ Transplant for People Living With HIV: Can Policy Catch Up to Outcomes Data?

“…There is wide racial disparity in the diagnosis and outcome of CKD in PLWH, much of it driven by factors similar to those identified in HIV-uninfected populations such as differential genetic susceptibility, 7 socioeconomic status, 8 and the use of race coefficients in equations for estimating glomerular filtration rate. 9 HIVAN was observed to be 18-fold more likely to occur in patients of African ancestry, and was the fourth leading cause of ESRD among Black individuals aged 20-64 y in 1994-1998.…”