Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial

Background Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 a-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH) 2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. Methods This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and 150 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extrarenal 1 alpha-hydroxylase was evaluated in endothelial cells of study participants. Findings Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T-50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial la-hydroxylase. Conclusion These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.