Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD-EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57-0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.