Proteinuria identifies patients at risk for adverse clinical outcomes, but it is unclear whether proteinuria correlates with the rate of renal decline. We examined the association between proteinuria and rate of change in estimated GFR (eGFR) in a cohort of 638,150 adults from a province-wide registry in Alberta, Canada, who had a measure of proteinuria and three or more outpatient serum creatinine measurements over a period of ≥1 year. An adjusted sex-specific linear mixed-effects model was used to determine the rate of change in eGFR per year for patients with normal, mild, and heavy proteinuria, stratified by baseline kidney function (eGFR ≥90, 60-89.9, 45-59.9, 30-44.9, and 15-29.9 ml/min per 1.73 m(2)). In men, heavy proteinuria and a baseline eGFR of 45-59.9 ml/min per 1.73 m(2) correlated with a change in eGFR of -2.16 (95% confidence interval [CI], -2.37 to -1.95) ml/min per 1.73 m(2) per year, whereas mild proteinuria and a baseline eGFR of 30-44.9 ml/min per 1.73 m(2) correlated with a change in eGFR of -0.51 (95% CI, -0.70 to -0.32) ml/min per 1.73 m(2) per year. Similar trends were observed for female, elderly, and diabetic patients. Notably, normal protein levels and a lower baseline eGFR (15-29.9 ml/min per 1.73 m(2)) correlated with stable or improved renal function. In conclusion, our results suggest that proteinuria of increasing severity is associated with a faster rate of renal decline, regardless of baseline eGFR, and the combined effect should be considered in patients with CKD.