title: Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial.
abstract: BACKGROUND
  Memory T-cells are mediators of transplant injury, and no therapy is known to prevent the development of cross-reactive memory alloimmunity. Activated vitamin D is immunomodulatory, and vitamin D deficiency, common in hemodialysis patients awaiting transplantation, is associated with a heightened alloimmune response. Thus, we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients.
  
  
  RESULTS
  We performed a 12-month single-center pilot randomized, controlled trial of 50,000 IU/week of cholecalciferol (D3) versus no supplementation in 96 hemodialysis patients with serum 25(OH)D<25 ng/mL, measuring effects on serum 25(OH)D and phenotypic and functional properties of T-cells. Participants were randomized 2:1 to active treatment versus control. D3 supplementation increased serum 25(OH)D at 6 weeks (13.5 [11.2] ng/mL to 42.5 [18.5] ng/mL, p<0.001) and for the duration of the study. No episodes of sustained hypercalcemia occurred in either group. Results of IFNγ ELISPOT-based panel of reactive T-cell assays (PRT), quantifying alloreactive memory, demonstrated greater increases in the controls over 1 year compared to the treatment group (delta PRT in treatment 104.8+/-330.8 vs 252.9+/-431.3 in control), but these changes in PRT between groups did not reach statistical significance (p = 0.25).
  
  
  CONCLUSIONS
  D3 supplements are safe, effective at treating vitamin D deficiency, and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients, but their effects on alloimmunity need to be confirmed in larger studies. These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01175798.
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Lily
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Marvin
authors.initials: M
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Krassilnikova
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Katya
authors.initials: K
authors.lastname: Ostrow
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bader
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Radbill
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Jaime
authors.initials: J
authors.lastname: Uribarri
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Joji
authors.initials: J
authors.lastname: Tokita
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Staci
authors.initials: S
authors.lastname: Leisman
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Vijay
authors.initials: V
authors.lastname: Lapsia
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Branch
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Recanati Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Anita
authors.initials: A
authors.lastname: Mehrotra
mesh_terms: D000284:Administration, Oral; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D010865:Pilot Projects; D006435:Renal Dialysis / Q000009:adverse effects*; D012449:Safety; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
chemical_list: D002762:Cholecalciferol