Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease: Results of the D-fense Trial

Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production.

A randomized controlled trial of daily vitamin D supplementation for 12 weeks was performed with the aim to test the effects of 4000 versus 400 IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children’s hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring.

A total of 34 subjects were randomized to either the intervention or control group, of whom 26.5% were female and 23.5% were African American. The mean age of the study cohort was 10.9 [standard deviation (SD) 5.8] years, the mean baseline glomerular filtration rate was 60 (SD 17.6) ml/min/1.73 m², and mean baseline 25D level was 29.7 (SD 11.5) ng/ml. At baseline, 50% of subjects were 25D deficient. There were no significant differences in baseline characteristics between the intervention and control groups. Treatment with 4000 IU cholecalciferol was not associated with significant change in hepcidin level at 4 or 12 weeks, and multivariable generalized estimating equation regression demonstrated no significant difference in change in hepcidin over the treatment period in either arm. The median C-reactive protein level decreased significantly at 12 weeks in the intervention group.

These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or those on dialysis.