PLoS ONE (Jan 2014)

Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial.

  • Lily Li,
  • Marvin Lin,
  • Maria Krassilnikova,
  • Katya Ostrow,
  • Amanda Bader,
  • Brian Radbill,
  • Jaime Uribarri,
  • Joji Tokita,
  • Staci Leisman,
  • Vijay Lapsia,
  • Randy A Albrecht,
  • Adolfo García-Sastre,
  • Andrea D Branch,
  • Peter S Heeger,
  • Anita Mehrotra

DOI
https://doi.org/10.1371/journal.pone.0109998
Journal volume & issue
Vol. 9, no. 10
p. e109998

Abstract

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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.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).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.Clinicaltrials.gov NCT01175798.