Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: A randomized controlled trial

Background & aims: Hypovitaminosis D and inflammation are highly prevalent among patients undergoing dialysis, and the association of both conditions with worse survival has been well recognized. Although a potential role for vitamin D in the immune system has been suggested, the effect of the treatment of hypovitaminosis D on the modulation of the inflammatory response remains unclear. The aim of this study was to investigate the effect of the restoration of the vitamin D status on the expression of vitamin D-regulatory proteins in monocytes and on circulating inflammatory markers in dialysis patients. Methods: In this randomized double-blind placebo-controlled 12-week trial, 38 patients on dialysis with serum 25-hydroxyvitamin D [25(OH)D] <20 ng/mL were randomized either to the cholecalciferol group (n = 20; 50,000 IU of cholecalciferol twice weekly) or to the control group (n=18; 50 drops of a placebo solution twice weekly). The expression of vitamin D receptor (VDR), CYP27B1, CYP24A1 and interleukin-6 (IL-6) in monocytes was determined by flow cytometry. Serum concentrations of 25(OH)D, interleukin-6 (IL-6), tumor necrosis factor-alpha (INF-alpha) and C-reactive protein (CRP) were measured. The trial is registered at ClinicalTrials.gov #NCT01974245. Results: After 12 weeks, the serum 25(OH)D increased from 14.3 +/- 4.7 ng/mL to 43.1 +/- 11.0 ng/mL (p < 0.05) in the cholecalciferol group and did not change in the control group (13.9 +/- 4.2 ng/mL to 13.5 +/- 4.3 ng/mL; p = 0.56). In monocytes, while CYP27B1 expression and VDR expression increased in the cholecalciferol group (p < 0.05), CYP27B1 expression did not change, and VDR expression decreased in the control group (p < 0.05). There were no changes in IL-6 and CYP24A1 expression in both groups. Serum concentration of IL-6 and CRP decreased from 8.1 +/- 6.6 pg/mL to 4.6 +/- 4.1 pg/mL (p < 0.05) and from 0.50 (0.10-1.27) mg/dL to 0.28 (0.09-0.62) mg/dL (p < 0.05), respectively only in the cholecalciferol group. Assessed overtime, the treatment group differences in 25(OH) D, PTH, CRP and IL-6, CYP27B1 and VDR remained significant. Conclusions: Restoration of vitamin D status of patients undergoing dialysis promoted upregulation of CYP27B1 and VDR expression in monocytes and a decrease in circulating inflammatory markers. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.