Comparative renoprotective effectiveness of allopurinol and febuxostat among hyperuricemic patients with preserved kidney function.

Objective: Early initiation of xanthine oxidase inhibitors (XOIs) may benefit patients with preserved kidney function. However, a direct comparison between the impact of allopurinol and those of febuxostat on long-term kidney function among this population is lacking.

Methods: We conducted a retrospective cohort study with a new-user, active-comparator design among patients with eGFR within the reference range and no proteinuria. The primary outcome was a composite incidence of significant eGFR decline (≥ 40% decline from baseline) and all-cause death at 5 years. Adjusted hazard ratios (HRs) were estimated using Cox's proportional hazard models with inverse probability of treatment and censoring weighting.

Results: We analyzed 1,142 patients (287 with allopurinol and 855 with febuxostat). The adjusted HRs (95% confidence intervals) for allopurinol initiators compared to febuxostat initiators for the composite outcome at 5 years were 0.84 (0.74-0.95). The cause-specific adjusted HRs for allopurinol initiators relative to febuxostat initiators were 0.82 (0.70-0.94) for significant eGFR decline over 5 years, and 1.08 (0.91-1.24) for all-cause death over 5 years.

Conclusion: Allopurinol initiators preserved kidney function better than febuxostat over 5 years. Clinicians should exercise caution not only when prescribing but also when selecting XOIs, even for patients with preserved kidney function.