A treat-to-target urate management strategy does not improve kidney outcome in patients with chronic kidney disease and asymptomatic hyperuricemia: a target trial emulation

BACKGROUND: Whether a treat-to-target urate management strategy improves kidney outcomes in patients with chronic kidney disease (CKD) and asymptomatic hyperuricemia initiating urate-lowering therapy (ULT) remains uncertain, despite current guidelines. METHODS: This target trial emulation (TTE) study included 2092 adults with stage G3-G4 CKD and asymptomatic hyperuricemia who initiated ULT at Zhejiang Provincial People's Hospital between 2018 and 2024. Using a clone-censor-weight (CCW) approach to address biases, we compared a treat-to-target strategy (targeting serum urate <360 μmol/L within 183 days) versus a non-treat-to-target strategy. Patients were followed for up to 3 years. The primary outcome was a composite kidney outcome: end-stage kidney disease (ESKD) or ≥40% eGFR decline. RESULTS: The 3-year absolute risk of composite kidney outcome was 33.3% (95% CI, 30.1%-36.6%) under the treat-to-target strategy and 35.8% (95% CI, 30.7%-40.5%) under the non-treat-to-target strategy, yielding a risk difference of -2.5% (95% CI, -6.5% to 2.5%) and a risk ratio of 0.93 (95% CI, 0.83-1.08). Subgroup analyses revealed no heterogeneity, and sensitivity analyses yielded consistent results. CONCLUSION: A treat-to-target urate management strategy was not associated with a reduced risk of composite kidney outcomes compared to a non-treat-to-target strategy. Among patients with stage G3-G4 CKD and asymptomatic hyperuricemia in whom clinicians decide to start ULT, these findings do not support pushing to achieve this intensive urate target for improving renal outcomes. As findings are largely based on a febuxostat-dominant real-world setting, extrapolation to other ULT agents may be limited.