Effect of cholecalciferol on serum hepcidin and parameters of anaemia and CKD-MBD among haemodialysis patients: a randomized clinical trial.

Abstract

In this multicentre double-blind randomized clinical trial, we investigated the effects of oral cholecalciferol supplementation on serum hepcidin and parameters related to anaemia and CKD-MBD among haemodialysis patients. Participants were assigned in a 2:2:1:1 ratio to either (1) thrice-weekly 3,000-IU cholecalciferol, (2) once-monthly cholecalciferol (equivalent to 9,000 IU/week), (3) thrice-weekly placebo, or (4) once-monthly placebo. We also examined the effect modifications by selected single nucleotide polymorphisms in vitamin D-related genes. Out of 96 participants, 94 were available at Month 3, and 88 completed the 6-month study. After adjustment for baseline values, serum hepcidin levels were higher at Day 3 in the combined cholecalciferol (vs. placebo) group, but were lower at Month 6 with increased erythropoietin resistance. Cholecalciferol increased serum 1,25(OH)2D levels, resulting in a greater proportion of patients who reduced the dose of active vitamin D at Month 6 (31% vs. 10% in the placebo group). Cholecalciferol also suppressed intact PTH only among patients with severe vitamin D deficiency. In conclusion, cholecalciferol supplementation increases serum hepcidin-25 levels in the short term and may increase erythropoietin resistance in the long term among haemodialysis patients. Both thrice-weekly and once-monthly supplementation effectively increases serum 1,25(OH)2D levels, and hence, reduces active vitamin D drugs.Clinical Trial Registry: This study was registered at ClinicalTrials.gov and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as NCT02214563 (registration date: 12/08/2014) and UMIN000011786 (registration date: 15/08/2014), respectively (please refer to the links below). ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/record/NCT02214563 . UMIN-CTR: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000017152&language=E .

• Authors: Yoshitsugu Obi, Satoshi Yamaguchi, Takayuki Hamano, Yusuke Sakaguchi, Akihiro Shimomura, Tomoko Namba-Hamano, Satoshi Mikami, Osamu Nishi, Motoko Tanaka, Akihito Kamoto, Yasue Obi, Naohisa Tomosugi, Yoshiharu Tsubakihara, Yoshitaka Isaka
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 15500 (09 23 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32968158 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hepcidins
• Vitamin D
• Cholecalciferol

Topics

• Aged
• Anemia (prevention & control, therapy)
• Cholecalciferol (administration & dosage, therapeutic use)
• Chronic Kidney Disease-Mineral and Bone Disorder (prevention & control, therapy)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Hepcidins (blood)
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Renal Dialysis (adverse effects, methods)
• Vitamin D (metabolism)