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.

METHODS AND FINDINGS:

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.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT01175798.

• Authors: 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
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e109998 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25296334 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cholecalciferol

Topics

• Administration, Oral
• Cholecalciferol (administration & dosage, adverse effects, pharmacology)
• Dietary Supplements (adverse effects)
• Female
• Humans
• Immunity, Cellular (drug effects)
• Inflammation (etiology, prevention & control)
• Male
• Middle Aged
• Monocytes (drug effects, immunology)
• Phenotype
• Pilot Projects
• Renal Dialysis (adverse effects)
• Safety
• T-Lymphocytes (drug effects, immunology)
• Time Factors