Abstract

BACKGROUND: Variability in kidney function, as measured by estimated glomerular filtration rate (eGFR), has been proposed as a novel risk factor for adverse cardiovascular outcomes. However, its association with incident heart failure (HF) in adults with type 2 diabetes remains unclear. OBJECTIVES: The aim of the study was to evaluate the association of eGFR variability with incident HF in a large sample of adults with type 2 diabetes. METHODS: We included participants who had ≥5 eGFR measurements in the first 24 months of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study. The visit-to-visit variability of eGFR was estimated using the coefficient of variation (CV), SD, and variability independent of the mean. Cox proportional hazards models were used to estimate adjusted HRs and 95% CIs for incident HF. RESULTS: Among 7,601 participants (mean age: 63 ± 6.5 years, 39.1% women, 63% White), 193 developed HF over a median follow-up of 3 years. HF incidence increased across quartiles of eGFR variability. In fully adjusted models, participants in the highest quartile of eGFR CV had an HR of 1.88 (95% CI: 1.09-3.22; P trend = 0.019) compared to the lowest quartile. Per 1-SD increments in all the eGFR variability metrics were associated with increased HF risk (CV: HR: 1.15; 95% CI: 0.99-1.33; SD: HR: 1.16; 95% CI: 1.01-1.33; variability independent of the mean: HR: 1.18; 95% CI: 1.03-1.35). CONCLUSIONS: Higher variability in eGFR is independently associated with an increased risk of incident HF in adults with type 2 diabetes.