The Effect of Febuxostat on Kidney Outcomes in Patients with Chronic Kidney Disease and Asymptomatic Hyperuricemia: A Target Trial Emulation

Background: Previous studies on the effects of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD) and asymptomatic hyperuricemia have yielded conflicting results regarding renal outcomes. This study aimed to investigate the impact of initiating febuxostat on kidney prognosis in patients with stage 3–4 CKD and asymptomatic hyperuricemia using real-world data. Methods: Using data from Zhejiang Provincial People’s Hospital, we conducted a target trial emulation study involving 3232 patients newly diagnosed with stage 3–4 CKD and asymptomatic hyperuricemia between January 1, 2018, and December 31, 2024. Using a clone-censor-weight approach, we compared the strategy of initiating febuxostat within one year of the first detected serum uric acid (UA) level >420 μmol/L versus to no initiation. Patients were followed for up to 5 years after hyperuricemia was diagnosed. The primary outcome was a composite kidney outcome consisting of a ≥40% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD) (eGFR <15 mL/min/1.73 m²), or initiation of kidney replacement therapy (KRT). Secondary outcomes included all-cause mortality and major adverse cardiovascular events (MACE). Results: Among patients newly diagnosed with CKD and hyperuricemia (mean age 71.8 years, 64% male, mean eGFR 42.8 mL/min/1.73 m², mean serum UA level 499.4 μmol/L), 631 individuals (20%) initiated febuxostat therapy. Compared with non-initiation, febuxostat initiation was not significantly associated with the primary composite kidney outcome (HR, 1.07; 95% CI, 0.91 to 1.20), all-cause mortality (HR, 1.00; 95% CI, 0.66 to 1.35), or MACE (HR, 1.03; 95% CI, 0.95 to 1.11). Conclusion: In patients with stage 3–4 CKD and asymptomatic hyperuricemia, initiation of febuxostat was not associated with kidney outcomes, all-cause mortality, or MACE. Further studies are warranted to validate these findings.