TY - JOUR
T1 - Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients
T2 - Data from a randomized controlled pilot trial
AU - Li, Lily
AU - Lin, Marvin
AU - Krassilnikova, Maria
AU - Ostrow, Katya
AU - Bader, Amanda
AU - Radbill, Brian
AU - Uribarri, Jaime
AU - Tokita, Joji
AU - Leisman, Staci
AU - Lapsia, Vijay
AU - Albrecht, Randy A.
AU - García-Sastre, Adolfo
AU - Branch, Andrea D.
AU - Heeger, Peter S.
AU - Mehrotra, Anita
N1 - Publisher Copyright:
© 2014 Bischoff et al.
PY - 2014/10/8
Y1 - 2014/10/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907833951&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0109998
DO - 10.1371/journal.pone.0109998
M3 - Article
C2 - 25296334
AN - SCOPUS:84907833951
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e109998
ER -