In a small pilot study, ergocalciferol reduced serum hepcidin levels in healthy individuals. So investigators speculated that vitamin D therapy might decrease hepcidin and increase iron for erythropoiesis in patients with chronic kidney disease (CKD). However, a new study published in BMC Nephrology finds that at least 1 vitamin D therapy, the activated vitamin D analog calcitriol, fails to improve hepcidin in patients with stage 3 to 4 CKD.

In a double-blind trial, a team led by Bhupesh Panwar, MD, of the University of Alabama at Birmingham, randomly assigned 40 patients with estimated glomerular filtration rates (eGFR) of 15 to 60 mL/min/1.73m2 to once daily oral calcitriol (0.5 mcg) or matching placebo for 6 weeks. The groups had similar baseline characteristics. Patients receiving erythropoiesis-stimulating agents or iron therapies were among those excluded.

Over 6 weeks, the team found no significant differences in the change in serum hepcidin over time or between the calcitriol and placebo groups, which started with median baseline levels of 71.7 and 76.1, respectively. Likewise, calcitriol therapy failed to improve serum ferritin, transferrin saturation, and hemoglobin levels.

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In patients treated with calcitriol, serum calcium and phosphorus significantly increased whereas parathyroid hormone significantly decreased. Hypercalcemia developed in 2 calcitriol-treated patients and 1 placebo recipient.

“In individuals with more advanced stages of CKD, hepcidin concentrations are elevated due to multiple factors (increased inflammation, reduced GFR, treatment with iron) that collectively could override any potential effect of vitamin D supplementation on inhibiting hepcidin expression,” Dr Panwar and colleagues wrote. “It is also possible that the nutritional forms of vitamin D that were used in prior studies are more efficacious in reducing hepcidin levels than the activated form (calcitriol) used in our study.”

The study included participants without vitamin D and iron deficiencies, which also might explain the overall lack of effect.

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Panwar B, McCann D, Olbina G, Westerman M, and Gutiérrez OM. Effect of calcitriol on serum hepcidin in individuals with chronic kidney disease: a randomized controlled trial. BMC Nephrol 2018;19:35. DOI 10.1186/s12882-018-0823-7