title: Immunomonitoring of nuclear factor of activated T cells-regulated gene expression: the first clinical trial in liver allograft recipients.
abstract: Long-term calcineurin inhibitor (CNI) treatment can cause serious side effects in liver allograft recipients. An optimal risk-to-benefit ratio for CNI blood levels has not been established. Pharmacodynamic drug monitoring through the measurement of the CNI biological activity, that is, the expression of nuclear factor of activated T cells (NFAT)-regulated genes, seems to be a promising approach. The residual gene expression (RGE) of NFAT-regulated genes 2 and 1.5 hours after cyclosporine A (CsA) and tacrolimus (FK-506) intake was measured in 100 liver allograft recipients with 1 or more years of follow-up post-transplantation. The mean RGE in all patients was 62% ± 33%. A significant negative correlation between the CsA (P < 0.0001, r = -0.8026) and FK-506 peak levels (P < 0.0001, r = -0.6982) and the RGE of all NFAT-regulated genes was observed. Clinical reliability was proven too. In conclusion, the data presented in this pilot study reveal the applicability of the pharmacodynamic monitoring of CNI efficacy in liver allograft recipients. To confirm the advantage of individualized pharmacodynamic drug monitoring over pharmacokinetic drug monitoring with respect to clinical outcomes, controlled, prospective studies are needed.
authors: Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany. alexandra.zahn@med.uni-heidelberg.de
authors: Alexandra
authors: A
authors: Zahn
authors: Nadja
authors: N
authors: Schott
authors: Ulf
authors: U
authors: Hinz
authors: Wolfgang
authors: W
authors: Stremmel
authors: Jan
authors: J
authors: Schmidt
authors: Tom
authors: T
authors: Ganten
authors: Daniel
authors: D
authors: Gotthardt
authors: Stefan
authors: S
authors: Meuer
authors: Martin
authors: M
authors: Zeier
authors: Thomas
authors: T
authors: Giese
authors: Claudia
authors: C
authors: Sommerer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000493:pharmacokinetics; D016903:Drug Monitoring; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000502:physiology*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000493:pharmacokinetics; D014184:Transplantation, Homologous
chemical_list: D065095:Calcineurin Inhibitors; D050778:NFATC Transcription Factors; D016572:Cyclosporine; D016559:Tacrolimus