Are allopurinol dose and duration of use nephroprotective in the elderly? A Medicare claims study of allopurinol use and incident renal failure.

Objective: To assess the effect of allopurinol dose/duration on the risk of renal failure in the elderly with allopurinol use.

Methods: We used the 5% random Medicare claims data from 2006 to 2012. Multivariable-adjusted Cox regression analyses assessed the association of allopurinol dose/duration with subsequent risk of developing incident renal failure or end-stage renal disease (ESRD) (no prior diagnosis in last 183 days) in allopurinol users, controlling for age, sex, race and Charlson-Romano comorbidity index. HRs with 95% CIs were calculated. Sensitivity analyses considered a longer baseline period (365 days), controlled for gout or used more specific codes.

Results: Among the 30 022 allopurinol treatment episodes, 8314 incident renal failure episodes occurred. Compared with 1-199 mg/day, allopurinol dose of 200-299 mg/day (HR 0.81; 95% CI 0.75 to 0.87) and ≥300 mg/day, 0.71 (0.67 to 0.76), had significantly lower hazard of renal failure in multivariable-adjustment model, confirmed in multiple sensitivity analyses. Longer allopurinol use duration was significantly associated with lower hazards in sensitivity analyses (365-day look-back; reference, <0.5 year): 0.5-1 year, 1.00 (0.88, 1.15); >1-2 years, 0.85 (0.73 to 0.99); and >2 years, 0.81 (0.67 to 0.98). Allopurinol ≥300 mg/day was also associated with significantly lower risk of acute renal failure and ESRD with HR of 0.89 (0.83 to 0.94) and 0.57 (0.46 to 0.71), respectively.

Conclusions: Higher allopurinol dose is independently protective against incident renal failure in the elderly allopurinol users. A longer duration of allopurinol use may be associated with lower risk of incident renal failure. Potential mechanisms of these effects need to be examined.