Association between allopurinol and mortality among Japanese hemodialysis patients: results from the DOPPS

PURPOSE: Allopurinol, for treating hyperuricemia, is associated with lower mortality among hyperuricemic patients without chronic kidney disease (CKD). Greater allopurinol utilization in hemodialysis (HD) in Japan versus other countries provides an opportunity for understanding allopurinol-related HD outcomes. METHODS: Data from 6,252 Japanese HD patients from phases 1–3 of the Dialysis Outcomes and Practice Patterns Study (1999–2008) at ~60 facilities per phase were analyzed. Mortality was compared for patients prescribed (25 %) versus not-prescribed allopurinol using Cox regression, overall, and in patient subgroups. RESULTS: Patients prescribed allopurinol were more likely to be younger, male, and non-diabetic, and had higher serum creatinine and lower (treated) serum uric acid levels (mean = 7.0 vs. 8.0 mg/dL, p < 0.001). The inverse association between allopurinol prescription and mortality in unadjusted analyses (HR 0.65, 95 % CI 0.52–0.81) was attenuated by covariate adjustment (HR 0.84, 0.66–1.06). In subgroup analyses, allopurinol was associated with lower mortality among patients with no history of cardiovascular disease (CVD) (HR 0.48, 0.28–0.83), but not among patients with CVD (HR 1.00, 0.76–1.32). A similar pattern was seen outside Japan and for cardiovascular (CV)-related mortality. CONCLUSIONS: Allopurinol prescription was not significantly associated with case-mix-adjusted mortality in Japanese HD patients overall, but was associated with lower all-cause and CV-related mortality in the subgroup of patients with no prior CVD history. These findings in HD patients may be related to findings in non-dialysis CKD patients showing lower CV event rates and mortality, and improved endothelial function with allopurinol prescription. These results are useful for designing future trials of allopurinol use in HD patients.