CHICAGO—Calcitriol and paricalcitol increase fibroblast growth factor 23 and sclerostin levels and decrease certain bone turnover markers while achieving sustained suppression of parathyroid hormone levels in patients with chronic kidney disease and secondary hyperparathyroidism, according to study findings presented at the American Society of Nephrology’s 2016 Kidney Week meeting.
The findings are from a post-hoc analysis of the PACE (Paricalcitol versus Calcitriol for Efficacy and Safety) study, an open-label phase 4 trial, which randomized 110 patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) to receive the drugs. Investigators performed primary analyses on 107 of them. The PACE study demonstrated that both vitamin D receptor agonists (VDRAs) had minimal effects on calcium and phosphorus. A team led by Stuart M. Sprague, DO, of North Shore University Health System—University of Chicago, conducted the post-hoc analysis because few studies have examined the effect of VDRAs on other mineral biomarkers in CKD patients.
Dr Sprague and his colleagues identified 76 of the 107 patients who had serum available for analysis at baseline and week 24. The calcitriol and paricalcitol groups each had 38 patients. The groups were well matched except for baseline intact parathyroid hormone (iPTH) level, which was higher in the calcitriol recipients (225 vs 168 pg/mL).
By week 24, both drugs had significantly decreased iPTH levels as well as the bone turnover markers bone-specific alkaline phosphatase (BSAP) and tartrate resistant acid phosphatase 5b (TRAP) and significantly increased levels of fibroblast growth factor 23 (FGF 23), and sclerostin, with no significant difference between both treatment groups. Paricalcitol, but not calcitriol, significantly increased 1,25 dihydroxyvitamin D levels.
In the calcitriol and paricalcitol groups, mean FGF-23 levels (in RU/mL) increased from 298 and 227 at baseline, respectively, to 482 and 418 at 24 weeks; mean sclerostin levels (in pmol/L) rose from 617 and 666 at baseline to 705 and 818 at 24 weeks. Mean BSAP levels (in µg/L) declined from 14.1 and 13.2 to 10.4 and 10.2; mean TRAP levels in U/L) declined from 4.49 and 3.21 to 3.42 and 2.48.
“Based upon the PACE trial, most patients with CKD have comparable PTH reduction with similar changes in calcium and phosphorus,” Dr Sprague told Renal & Urology News. “Both VDRAs, comparably increase FGF23 and sclerostin. Further studies are required to determine whether increases in FGF 23 may have systemic detrimental effects and increases in sclerostin may contribute to low bone turnover.”
- Sprague SM, et al. Effect of active vitamin D therapy on CKD-MBD biomarkers in CKD patients: A post hoc analysis of the PACE trial. Presented as a poster at the 2016 Kidney Week meeting in Chicago, Nov. 15-20.