Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients : data from a randomized controlled pilot trial
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
PloS one - 9(2014), 10 vom: 07., Seite e109998 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Lily [VerfasserIn] |
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| Links: |
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| Themen: |
1C6V77QF41 |
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| Anmerkungen: |
Date Completed 09.10.2015 Date Revised 21.10.2021 published: Electronic-eCollection ClinicalTrials.gov: NCT01175798 Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0109998 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM242602150 |
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| 245 | 1 | 0 | |a Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients |b data from a randomized controlled pilot trial |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a ClinicalTrials.gov: NCT01175798 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a TRIAL REGISTRATION: Clinicaltrials.gov NCT01175798 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Cholecalciferol |2 NLM | |
| 650 | 7 | |a 1C6V77QF41 |2 NLM | |
| 700 | 1 | |a Lin, Marvin |e verfasserin |4 aut | |
| 700 | 1 | |a Krassilnikova, Maria |e verfasserin |4 aut | |
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| 700 | 1 | |a Bader, Amanda |e verfasserin |4 aut | |
| 700 | 1 | |a Radbill, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Uribarri, Jaime |e verfasserin |4 aut | |
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| 700 | 1 | |a Heeger, Peter S |e verfasserin |4 aut | |
| 700 | 1 | |a Mehrotra, Anita |e verfasserin |4 aut | |
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