title: Clinical Significance of the Pharmacological Efficacy of Tacrolimus Estimated by the Lymphocyte Immunosuppressant Sensitivity Test (LIST) Before and After Renal Transplantation.
abstract: The lymphocyte immunosuppressant sensitivity test (LIST) with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay procedure can predict the pharmacological efficacy of immunosuppressive agents. A previous study reported the pharmacological efficacy of tacrolimus evaluated by LIST just before renal transplantation significantly correlated with the incidence of acute rejection episodes. However, the pharmacological efficacy of tacrolimus has not been estimated after renal transplantation. Therefore, the present study evaluated the pharmacological efficacy of tacrolimus by LIST using the MTT assay procedure before and 1, 3, and 12 months after transplantation in 17 renal transplant recipients that received tacrolimus-based immunosuppressive therapy. The tacrolimus pharmacological efficacies before and after the procedure were also compared with incidence of acute rejection and cytomegalovirus (CMV) infection episodes. The individual values of tacrolimus 50% inhibition of lymphocyte proliferation (IC50) varied widely before transplantation, and the mean value of the IC50 was 126.4 ± 337.7 ng/ml. The patients were divided into two groups according to the tacrolimus IC50 values evaluated before transplantation. The rate of acute rejection episodes in the tacrolimus high-sensitivity group was significantly lower than that in the tacrolimus low-sensitivity group (p= 0.005). The tacrolimus IC50 deviation between patients expanded further at one and three months after surgery. However, the sensitivity deviation almost converged at 1 year after surgery. Moreover, the pharmacological efficacy of tacrolimus evaluated at 1, 3, and 12 months after transplantation did not significantly correlate with the incidence of acute rejection episodes. The pharmacological efficacies of tacrolimus evaluated at both before and after surgery were not significantly correlated with the episodes of CMV infection. These findings suggest that the pharmacological efficacy of tacrolimus evaluated with LIST before surgery is a useful biomarker for predicting the occurrence of acute allograft rejection in renal transplantation.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Tokyo , Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: † Division of Pharmacy, Niigata University Medical and Dental Hospital , Niigata , Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Isogai
authors.affiliation: † Division of Pharmacy, Niigata University Medical and Dental Hospital , Niigata , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Toyama
authors.affiliation: † Division of Pharmacy, Niigata University Medical and Dental Hospital , Niigata , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satoh
authors.affiliation: ‡ Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University , Niigata , Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Saito
authors.affiliation: ‡ Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University , Niigata , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: ‡ Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University , Niigata , Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: ‡ Division of Urology, Graduate School of Medical and Dental Sciences, Niigata University , Niigata , Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Tokyo , Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
keywords: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT); Lymphocyte immunosuppressant-sensitivity test (LIST); Peripheral-blood mononuclear cells (PBMCs); Renal transplantation; Tacrolimus