Differential associations of febuxostat and allopurinol with incident and worsening frailty risk in nephrology patients.

BACKGROUND

Hyperuricemia and gout are linked to adverse outcomes and may influence frailty risk, but evidence on the impact of uric acid (UA)-lowering therapy on frailty among nephrology patients is limited. We evaluated the association of febuxostat and allopurinol use with incident and worsening frailty in a large nephrology patient cohort.

METHODS

This retrospective cohort study included 19,389 adults attending nephrology clinics at a tertiary medical center in Taiwan between 2013 and 2021 with available UA and estimated glomerular filtration rate (eGFR) data. Exposure was the use of febuxostat, allopurinol, or both agents versus no UA-lowering therapy. We examined incident frailty and worsening frailty defined by the FRAIL scale after follow-up. Kaplan-Meier and Cox proportional hazards models were applied, adjusting for demographics, comorbidities, medications, baseline frailty, and laboratory data.

RESULTS

Over a median follow-up of 3.0 years, 892 (4.6%) participants developed incident frailty and 5,253 (27.1%) had worsening frailty. After adjustment, febuxostat use was associated with higher probability of incident frailty (hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.01-1.48), while allopurinol use was associated with lower probability (HR 0.65, 95% CI 0.46-0.93) compared to non-users. Both users had no alterations in incident frailty probability. Neither therapy was significantly associated with worsening frailty. Subgroup analyses showed modification effects from age and eGFR levels.

CONCLUSIONS

Among nephrology patients, UA-lowering therapy showed divergent associations with frailty probability: febuxostat use correlated with higher whereas allopurinol use correlated with lower incident frailty probability, with no effect on frailty progression. Choice of UA-lowering therapy may have implications for functional outcomes in this high-risk population.