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

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

We conducted a retrospective cohort study with a new-user, active-comparator design among patients with estimated glomerular filtration rate (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 were estimated using Cox's proportional hazard models with inverse probability of treatment and censoring weighting.

We analysed 1142 patients (287 with allopurinol and 855 with febuxostat). The adjusted hazard ratios (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 hazard ratios for allopurinol initiators relative to febuxostat initiators were 0.82 (0.70-0.94) for significant eGFR decline >5 years and 1.08 (0.91-1.24) for all-cause death >5 years.

Allopurinol initiators preserved kidney function better than febuxostat >5 years. Clinicians should exercise caution not only when prescribing but also when selecting xanthine oxidase inhibitors, even for patients with preserved kidney function.