Therapeutics and Clinical Risk Management (Aug 2017)
Effect of additive calcium administration on FGF23 levels in patients with mild chronic kidney disease treated with calcitriol: a randomized, open-labeled clinical trial
Abstract
Nayoung Han,1,* Su Hyun Hong,1,2,* Yon Su Kim,3 Dong Ki Kim,3 In-Wha Kim,1 Eunhee Ji,4 Jung Mi Oh1 1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 2Pharmaceutical Standardization Division, Drug Evaluation Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungcheongbuk-do, 3Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, 4College of Pharmacy, Gachon University, Incheon, Republic of Korea *These authors contributed equally to this work Background: The purpose of the present study was to determine the effect of additional calcium carbonate treatment on fibroblast growth factor 23 (FGF23) levels in patients treated with calcitriol.Methods: In this randomized, open-labeled, and parallel-group study, a total of 30 patients with early chronic kidney disease (CKD) and vitamin D deficiency were randomly assigned to two groups and received interventions for 8 weeks: 1) a combination of calcium carbonate and calcitriol group; and 2) calcitriol only group. The primary outcome was the difference in percentage change of serum FGF23 levels from baseline between the two groups. Secondary end points included the changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), and 25-hydroxyvitamin D3 (25(OH)D) from baseline.Results: Serum FGF23 levels were more elevated in the combination group than in the calcitriol-alone group. However, both mean change and percentage change in the serum FGF23 levels during the 8-week period were not significantly different between the two groups. Serum calcium level was increased significantly only in the combination treatment group. There was no significant difference in percentage change of serum calcium levels between the two groups. In addition, changes in serum levels of phosphate, 25(OH)D, or PTH were not significantly different between the two groups. In correlation analysis, changes in serum FGF23 levels were positively correlated with changes in serum calcium and phosphate levels, but not with changes in 25(OH)D or PTH levels. No serious adverse events were observed, however, there was one case of mild gastrointestinal discomfort.Conclusion: This study revealed that additional calcium carbonate treatment significantly increased serum FGF23 levels in patients treated with calcitriol, with their synergistic effect in promoting intestinal calcium absorption. This suggests that serum FGF23 levels should be monitored regularly, especially in those who use combination of vitamin D and calcium carbonate from the early stages of CKD. Keywords: fibroblast growth factor-23, vitamin D deficiency, calcium carbonate, calcitriol, mineral and bone disorder
