Background
Estimated glomerular filtration rate (eGFR) and albuminuria are central for diagnosis, staging, and risk evaluation in chronic kidney disease (CKD). Universal thresholds regardless of age, sex, and race are recommended, but relatively little is known about how these demographic factors alter the relationship of eGFR and albuminuria to cardiovascular outcomes.
Study Design
Observational cohort study.
Setting & Participants
11,060 whites and blacks aged 52–75 years in the Atherosclerosis Risk in Communities (ARIC) Study with median follow-up of 11.2 years.
Predictors
eGFR by the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation (reference, 95 ml/min/1.73 m2) and urinary albumin-creatinine ratio (ACR) (reference, at 5 mg/g).
Outcomes
Cardiovascular events (coronary disease, stroke, and heart failure) and all-cause mortality.
Measurements
Adjusted HRs associated with eGFR and ACR in subgroups according to age, sex and race.
Results
Cardiovascular risk significantly increased at eGFR <70 ml/min/1.73 m2 in all subgroups according to age (< 65 vs. ≥65 years), sex, and race (P for interaction >0.2 for these subgroups; e.g., at eGFR 30 ml/min/1.73 m2, the adjusted HR was 2.19 [95% CI, 1.10–4.35] at age 52–64 years vs. 2.23 [95% CI, 1.33–3.72] at age 65–75 years). Results were similar for mortality. Log(ACR) was linearly associated with cardiovascular risk without threshold effects in all subgroups, with some quantitative interactions. HRs according to ACR tended to be lower in men vs. women (e.g., at ACR 40 mg/g, 1.18 [95% CI, 0.98–1.41] vs. 1.77 [95% CI, 1.45–2.15]) and in older vs. younger population (1.24 [95% CI, 1.04–1.49] vs. 1.73 [95% CI, 1.42–2.12]) (P for interaction <0.01 for sex and age). Less evident interactions were observed for mortality.
Limitations
Single measurement of eGFR with creatinine and ACR and relatively narrow age range.
Conclusions
The associations of eGFR and ACR with cardiovascular events were largely similar, with some quantitative interactions, among age, sex, and racial subgroups, generally supporting universal thresholds of GFR and ACR for CKD definition/staging.