Abstract

Vitamin D has been shown to be a regulator of hepcidin-ferroportin axis. Vitamin D deficiency is common in CKD. Whether native vitamin D supplementation favorably affects serum hepcidin in CKD is not known. We investigated the effect of cholecalciferol supplementation on serum hepcidin levels in non-diabetic patients with CKD stage 3-4. In this secondary analysis of our previously published randomized, double-blind, placebo-controlled trial(https://jasn.asnjournals.org/content/28/10/3100), stable patients of either sex, aged 18-70 years, with non-diabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in FMD at 16 weeks. Serum level of Hepcidin was analyzed by ELISA (Quantikine®ELISA kit, R&D, Minneapolis, MN, USA). Intra-assay and inter-assay coefficient of variation of this kit was 3.2-4.3% and 6.2-11%, respectively. Changes in serum hepcidin levels between groups over 16 weeks were compared using paired t test. 120 patients were enrolled. Baseline characteristics showed no differences between groups with respect to demographic details and causes of CKD. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21±4.78 ng/ml and13.40±4.42ng/ml; P=0.88). At16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group(between-group difference in mean change:23.40 ng/ml; 95% CI, 19.76 to27.06; P<0.001). Blood levels of hemoglobin were similar at baseline (12.02±1.94 mg/dl vs 11.97±1.69mg/dl, p=0.947) and there were no significant changes at 16 weeks in either group [between group difference; 0.21 (-0.22 to 0.63), p=0.34]. Serum hepcidin levels were similar at baseline [median (IQR): 33.6 (8.6-77.8) ng/ml vs 24.6 (9.3-70.7) ng/ml, p=0.903] and did not vary between groups at 16 week [median (IQR): 41.5 (10.9-75.0) ng/ml vs34.8(12.3-63.75) ng/ml, p=0.703]. High dose oral cholecalciferol supplementation has no effect on serum hepcidin levels in subjects with non-diabetic CKD stage 3-4.

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