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

Why clinicians should know about it

• Picked for Nephrology (paper of the day, 25 August 2026): Retrospective CKD cohort linking FEUA, ULT to kidney outcomes

Abstract

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.

Abstract as published, via PubMed.