Allopurinol has no effect on calcitriol or other CKD-MBD biomarkers: a randomized double-blind study

Introduction New evidence has emerged linking uric acid levels to Chronic Kidney Disease and Mineral and Bone Disorder (CKD-MBD). However, interventional studies remain scarce. We evaluated the effect of allopurinol on CKD-MBD biomarkers. Methods This is a randomized, double-blind clinical trial involving adult patients with stage 3-5 CKD under conservative management. Participants received either allopurinol 300mg or placebo for at least 90 days. Clinical data and blood samples were collected at baseline and at the end of the follow-up period to assess changes in calcium, phosphate, 25-hydroxyvitamin-D, parathyroid hormone (PTH), 1,25-hydroxyvitamin D, fibroblast growth factor 23 (FGF23), α Klotho, and bone alkaline phosphatase. Results Forty-nine patients completed the study (25 in the allopurinol group and 24 in the placebo). Most participants were women (53,1%), with a mean age of 71±11 years and an average eGFR of 27.8 ± 11.0 ml/min/1.73m2. Uric acid levels were significantly decreased in the allopurinol group (7.49mg/dl initial vs. 3.96mg/dl final, 43%, p< 0.001). FGF23 levels increased over time (p = 0.037), with no difference between groups. 25-hydroxyvitamin-D levels increased in allopurinol group and decreased in the placebo group, a result that lost significance after adjusting for cholecalciferol supplementation, and race. No other CKD-MBD biomarker were significantly affected by allopurinol treatment. Conclusion Despite its urate-lowering effect, allopurinol did not produce meaningful changes in the major CKD-MBD biomarkers over the study period. Our results strengthen existing recommendations to restrict uric acid-lowering treatment to symptomatic gout, as we did not identify any associated improvements in mineral metabolism.