Allopurinol and Alkaline Phosphatase Levels in Patients with Non-Dialysis CKD

Background: Inhibition of xanthine oxidase with allopurinol increases bone alkaline phosphatase (ALP) in vitro, while ALP promotes bone and vascular mineralization and is linked to reduced survival in general and renal populations. However, clinical associations between allopurinol use and ALP have not yet been reported. We examined prospective associations between allopurinol use, ALP levels, and death in patients with non-dialysis CKD. Population and Setting: A total of 1636 multi-ethnic patients enrolled in the CAN AIM to PREVENT, a 3-year prospective observational study in Toronto, Canada. Primary Outcomes: ALP levels and the combination of renal and patient deaths. Statistical Analyses: Joint generalized structural equation modeling, causal mediation, and controlled direct effects. Results: Allopurinol use was associated with increased ALP (18.3% (95% CI: 10.9, 26.2, p < 0.001)) but not renal and patient death (HR = 1.32 (0.87, 1.99, p = 0.193)). The association between allopurinol and ALP was most pronounced when PTH and urate were low, and was partially mediated by PTH (7.9%, (p = 0.006)). Limitations: Observational and post hoc designs prevent causal inferences. Lack of data about specific ALP isoforms. Conclusions: Allopurinol use was associated with increased ALP but not renal or patient deaths in patients with non-dialysis CKD. Future studies can confirm the generalizability to other clinical populations and examine mechanisms and clinical significance.