title: Influence of cholecalciferol supplementation in hemodialysis patients on monocyte subsets: a randomized, double-blind, placebo-controlled clinical trial.
abstract: OBJECTIVE
  Although most hemodialysis patients share a significant 25-hydroxyvitamin D [25(OH)D] deficiency, supplementation is controversially discussed. A potential influence on monocyte and T lymphocyte dysfunction advocates blood level-adapted supplementation as recommended by K/DOQI guidelines. This was a prospective double-blind randomized placebo controlled trial examining immune effects of 12 weeks of cholecalciferol supplementation.
  
  
  METHODS
  We initiated serum level-adapted de novo cholecalciferol supplementation in 38 hemodialysis patients. Outcome measures were: monocyte subset cell counts (CD14+CD16++ vs. CD14++CD16+ vs. CD14++CD16-), lymphocyte Th1/Th2 differentiation frequencies, serum inflammatory proteins CRP and TNFα, parathyroid hormone (PTH), FGF-23, and α-Klotho.
  
  
  RESULTS
  At baseline, the mean 25(OH)D serum level in the study population was 31.7 ± 14.3 nmol/l, and only 3% of patients had levels within the normal range. At 12 weeks, 25(OH)D levels were normalized in the verum group (87.8 ± 22.3 vs. placebo 24.6 ± 8.0 nmol/l, p < 0.0001). In parallel, 1,25(OH)2D levels increased in the verum group. Monocyte subset cell counts as well as Th1 and Th2 lymphocyte frequencies did not change significantly after 12 weeks of cholecalciferol supplementation. There was also no significant difference in PTH, alkaline phosphatase, calcium, phosphate, TNFα, FGF-23, α-Klotho and CRP levels.
  
  
  CONCLUSIONS
  Oral cholecalciferol supplementation according to the K/DOQI recommendations normalizes 25(OH)D levels without relevant side effects such as hyperphosphatemia or hypercalcemia. However, beneficial pleiotropic effects on monocyte subset cell counts, T cell differentiation, or cytokine production could not be confirmed at least at the used dosage. PTH and FGF23 levels were not affected during cholecalciferol administration.
authors.affiliation: Internal Medicine II, Martin Luther University of Halle-Wittenberg Medical Centre, Halle, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Seibert
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
authors.forename: Christof
authors.initials: C
authors.lastname: Ulrich
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler
authors.forename: Hans
authors.initials: H
authors.lastname: Köhler
authors.forename: Matthias
authors.initials: M
authors.lastname: Girndt
mesh_terms: D000368:Aged; D001842:Bone and Bones / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D011446:Prospective Studies; D006435:Renal Dialysis; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D002762:Cholecalciferol; C097949:1,25-dihydroxyvitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D