Urate-lowering therapy modifies associations between urinary urate and kidney outcome

Background Serum uric acid is associated with chronic kidney disease (CKD) progression; however, causality remains uncertain. Although renal urate handling, rather than merely hyperuricemia, may dominate kidney outcomes, the prognostic value of urinary urate indices and the potential modifying effect of urate-lowering therapy (ULT) remain unclear.Methods This retrospective study included patients with an estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73m2. Exposures were fractional excretion of uric acid (FEUA) and the urinary uric acid-to-creatinine ratio (UUCR). Major adverse kidney event (MAKE) was defined as ≥40% decline in eGFR, initiation of kidney replacement therapy, or death. Associations between FEUA and MAKE, and the modifying effect of ULT were evaluated using Kaplan–Meier analyses and multivariable Cox proportional hazards models, including stratification by baseline ULT.Results Among 551 patients (244 receiving ULT), 117 experienced MAKE over a median follow-up of 2.3 years. In the adjusted analysis, FEUA <5.5% was associated with a higher overall risk (hazard ratio [HR], 3.56; 95% CI, 1.96–6.48), with a stronger association in the no-ULT group (HR, 11.59; 95% CI, 3.80–35.31). Conversely, FEUA was not associated with the outcome within the ULT group. FEUA × ULT interaction was significant, indicating that the prognostic meaning of FEUA depends on concomitant ULT.Conclusion: Reduced urinary urate excretion was associated with a higher risk for MAKE. ULT modifies the prognostic impact of FEUA, underscoring the clinical relevance of renal urate handling when assessing kidney risk in CKD and suggesting that pharmacological urate-lowering may modify this risk.