Mild Albuminuria Is a Risk Factor for Faster GFR Decline in the Nondiabetic Population

Introduction: A minimal increase in the albumin-to-creatinine ratio (ACR) predicts cardiovascular disease and mortality, but whether it predicts kidney function loss in nondiabetic persons is unclear. We investigated the association between ACR in the optimal or high-normal range and the rate of glomerular filtration rate (GFR) decline in a cohort from the general population without diabetes, cardiovascular, or chronic kidney disease. Methods: In the Renal Iohexol Clearance Survey, we measured GFR using iohexol clearance in 1567 middle-aged nondiabetic individuals with an ACR <3.40 mg/mmol (30.0 mg/g) at baseline. The ACR was measured in unfrozen morning urine samples collected on 3 days before the GFR measurements. A total of 1278 (81%) participants had follow-up with GFR measurements after a median of 5.6 years. Results: The median ACR at baseline was 0.22 mg/mmol (interquartile range: 0.10−0.51 mg/mmol), the mean ± SD GFR was 104.0 ± 20.1 ml/min, and the mean ± SD GFR decline rate was −0.95 ± 2.23 ml/min per year. Higher baseline ACR levels were associated with a steeper GFR decline in adjusted linear mixed models. Study participants with ACR levels of 0.11 to 0.45 and 0.46 ± 3.40 mg/mmol had a 0.25 ml/min per year (95% confidence interval [95% CI]: −0.03 to 0.53) and 0.31 ml/min per year (95% CI: 0.02−0.60) steeper rate of decline than those with ACR ≤0.10 mg/mmol in multivariable-adjusted analyses. Among study participants with an ACR of