Effect of calcitriol on serum hepcidin in individuals with chronic kidney disease: a randomized controlled trial

Bhupesh Panwar, Diane McCann, Gordana Olbina, Mark Westerman, Orlando M Gutiérrez, Bhupesh Panwar, Diane McCann, Gordana Olbina, Mark Westerman, Orlando M Gutiérrez

Abstract

Background: Anemia is highly prevalent in chronic kidney disease (CKD). Elevated hepcidin concentrations are an important mediator of disordered iron metabolism, a key mechanism underlying anemia of CKD. Vitamin D was recently shown to reduce serum hepcidin concentrations in healthy individuals. We examined whether treatment with calcitriol reduces serum hepcidin in individuals with CKD.

Methods: A total of 40 participants with stage 3 or 4 CKD (eGFR 15-60 ml/min/1.73m2) were randomized to receive either oral calcitriol 0.5 mcg daily or identically-matched placebo for 6 weeks. The primary outcome variable was change in serum hepcidin concentrations. Secondary outcomes variables included the change in iron parameters, calcium, phosphorus, intact parathyroid hormone and hemoglobin concentrations. Study samples were drawn at baseline, 3 days, 1 week, 4 weeks and 6 weeks after randomization. Repeated measures analysis was used to examine differences in outcome variables over time in the two groups.

Results: There were no significant differences in the baseline characteristics between the placebo and calcitriol arms. Over 6 weeks of follow-up there were no significant differences in the change in serum hepcidin, iron parameters, or hemoglobin between the two groups. Serum calcium and phosphorus significantly increased and PTH significantly decreased after 6 weeks in calcitriol group whereas these analytes did not change in the placebo group.

Conclusion: Calcitriol did not reduce serum hepcidin concentrations among individuals with mild to moderate CKD. Future studies are needed to assess if nutritional forms of vitamin D affect hepcidin concentrations in CKD.

Trial registration: ClinicalTrials.gov Identifier: NCT01988116 . Registered: November 4, 2013.

Keywords: Anemia of CKD; Calcitriol; Chronic kidney disease; Hepcidin; Vitamin D.

Conflict of interest statement

Ethics approval and consent to participate

Study protocol and consent was approved by the University of Alabama Ethics Committee. Study participants provided written informed consent to participate.

Consent for publication

Not applicable

Competing interests

Dr. Gutierrez reports receiving consulting fees and grant support from Keryx Biopharmaceuticals. Drs. Westerman and Olbina and Ms. McCann are employees of Intrinsic LifeSciences. Drs. Westerman and Olbina own stock in Intrinsic LifeSciences.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Overview of the study design
Fig. 2
Fig. 2
Study flow diagram depicting participant screening, enrollment, intervention allocation, and follow-up
Fig. 3
Fig. 3
Change in serum hepcidin, median [IQR]; ferritin, median [IQR]; transferrin saturation, mean (±SD); hemoglobin, mean(±SD) over time by treatment group
Fig. 4
Fig. 4
Change in mean(±SD) serum calcium, phosphorus, and PTH over time by treatment group

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