Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: A randomized controlled trial
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2016
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Meireles, Marion Schneider [UNIFESP]
Kamimura, Maria Ayako [UNIFESP]
Dalboni, Maria Aparecida [UNIFESP]
Carvalho, José Tarcisio Giffoni de [UNIFESP]
Aoike, Danilo Takashi [UNIFESP]
Cuppari, Lilian [UNIFESP]
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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.
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.
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Clinical Nutrition. Edinburgh, v. 35, n. 6, p. 1251-1258, 2016.