title: Effect of cholecalciferol on vitamin D-regulatory proteins in monocytes and on inflammatory markers in dialysis patients: A randomized controlled trial.
abstract: 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.
  
  
  
  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-α (TNF-α) and C-reactive protein (CRP) were measured. The trial is registered at ClinicalTrials.gov #NCT01974245.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: The Nutrition Graduation Program, Federal University of São Paulo, Brazil. Electronic address: mariondschneider@gmail.com.
authors.forename: Marion Schneider
authors.initials: MS
authors.lastname: Meireles
authors.affiliation: The Nutrition Graduation Program, Federal University of São Paulo, Brazil. Electronic address: m.kamimura@uol.com.br.
authors.forename: Maria Ayako
authors.initials: MA
authors.lastname: Kamimura
authors.affiliation: Department of Medicine, Division of Nephrology, Federal University of São Paulo, Brazil. Electronic address: dalboni@nefro.epm.br.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Dalboni
authors.affiliation: Department of Medicine, Division of Nephrology, Federal University of São Paulo, Brazil. Electronic address: tarcisiogiffoni@yahoo.com.br.
authors.forename: José Tarcísio
authors.initials: JT
authors.lastname: Giffoni de Carvalho
authors.affiliation: Department of Medicine, Division of Nephrology, Federal University of São Paulo, Brazil. Electronic address: aoike@ig.com.br.
authors.forename: Danilo Takashi
authors.initials: DT
authors.lastname: Aoike
authors.affiliation: The Nutrition Graduation Program, Federal University of São Paulo, Brazil; Department of Medicine, Division of Nephrology, Federal University of São Paulo, Brazil. Electronic address: lcuppari@uol.com.br.
authors.forename: Lilian
authors.initials: L
authors.lastname: Cuppari
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001938:Brazil; D002097:C-Reactive Protein / Q000032:analysis; D002762:Cholecalciferol / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry*; D010919:Placebos; D018167:Receptors, Calcitriol / Q000097:blood; D006435:Renal Dialysis; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*; D065668:Vitamin D3 24-Hydroxylase / Q000097:blood
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D010919:Placebos; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; D002762:Cholecalciferol; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
keywords: Chronic kidney disease; Dialysis; Inflammation; Vitamin D