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논문분류	춘계학술대회 초록집
제목	Monitoring Intracellular Tacrolimus Concentration in Kidney Transplant Recipients with Stable Graft Function
저자	Seung Seok Han1, Eunjin Bae1, Seung Hee Yang2, Joo-Youn Cho3, Hajeong Lee1, Jung Pyo Lee1, Dong Ki Kim1, Yon Su Kim1
출판정보	2015; 2015(1):
키워드	타크로리무스,신장 이식,농도
초록	Background: Monitoring the intracellular concentrations of immunosuppressive agents can be a promising approach to improve and individualize the clinical practice in patients undergoing transplantation. However, the utility of monitoring intracellular tacrolimus level in kidney transplant recipients remains unresolved. Methods: Both whole blood and intracellular concentrations of tacrolimus (WB-TAC and IC-TAC, respectively) were measured simultaneously in 213 kidney recipients with stable graft function using LC-MS/MS. The tacrolimus ratio was defined as the ratio between IC-TAC and WB-TAC (IC-TAC/WB-TAC). In addition, the genetic polymorphisms of the ATP-binding cassette subfamily B member 1 (ABCB1), including rs1128503, rs2032582, and rs1045642, were examined. Flow cytometry was used to determine the proportion of T cells producing interferon gamma or interleukin 2 according to IC-TAC levels (Fig. 1). Results: The levels of WB-TAC, IC-TAC, and the tacrolimus ratio were 4.6±1.83 ng/mL, 43.4±30.10 pg/106 cells, and 9.3±4.25, respectively. The correlation coefficient (r) between WB-TAC and IC-TAC was 0.67 (p<0.001). Genetic polymorphisms of ABCB1 were not associated with either IC-TAC or the tacrolimus ratio. Among baseline covariates, sex, hematocrit and the transplant duration were significant predictors of the tacrolimus ratio: a high tacrolimus ratio was present in females, in patients with a low hematocrit, or in an early transplant period. After stimulation with PMA and ionomycin, the proportion of T cells producing interferon gamma or interleukin 2 was higher in the group with lower IC-TAC levels. Conclusions: This is the first study to identify factors associated with the ratio between blood and intracellular tacrolimus levels in kidney transplant recipients. Results from this study will be helpful in monitoring and predicting intracellular tacrolimus concentrations.
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