Calcitriol reduces the occurrence of acute cellular rejection of liver transplants: a prospective controlled study

Abstract

Objective: To investigate the acute cellular rejection rate of liver transplant recipients taking or not taking calcitriol in a prospective, randomized, controlled clinical study.

Methods: Primary liver transplant patients were randomized to receive the placebo (arm A), calcium gluconate (arm B) or calcium gluconate plus calcitriol (arm C). The composition of circulating T cell subpopulations was determined by flow cytometry at baseline and one week post transplant. The primary endpoint was acute cellular rejection rate at one month post transplant.

Results: Seventy-five liver transplant recipients were eligible, including 25 patients each in arm A, B and arm C. The mean baseline serum 25-(OH) vitamin D content was 12.5 +/- 3.0 (range, 2.5 to 19.5) ng/mL, with no statistical difference among the three arms. Among 7 (9.33%) patients who developed definite acute cellular rejection (Banff score > or = 6), only 1 (4%, 1/25) were from arm C while 6 (12%, 6/50) of them were from either arm A or B. The acute cellular rejection rate was 20% (5/25) for arm C, 32% (8/25) for arm A and 28% (7/25) for arm B (arm C vs. arm A or B, P < 0.05). Flow cytometric analysis showed that the proportion of circulating CD4+ CD25(high) CD(127-)(Treg) cells in arm C increased by 63.22% at one week post transplant (3.95 +/- 4.0%) compared to baseline (2.42 +/- 2.35%) (P < 0.05). No significant difference was observed in arm A or B (P > 0.05 in both vs. baseline). Furthermore, no significant difference was noted among the three arms in the proportion of CD4(+)CD45RA(-)CD45RO(+), CD4(+)CD25(low)CD45RA(+) and CD4(+)CD25(low)CD45RA(-) T cells at one week post transplant compared to baseline.

Conclusion: Calcitriol has apparent beneficial effect on acute cellular rejection of liver transplants, which may be associated with increases in the proportion of circulating Treg cells.