title: Initial liver graft function is a reliable predictor of tacrolimus trough levels during the first post-transplant week.
abstract: The narrow therapeutic range of tacrolimus requires careful management after liver transplantation (LT). The aim of this study was to investigate the influence of graft function on tacrolimus trough levels during the first post-transplant week. Ninety-three patients receiving deceased-donor LT were observed in a prospective observational study. Graft function was determined by the new LiMAx test (maximal liver function capacity). Significant correlations between LiMAx readouts and consecutive tacrolimus levels, up to r = -0.529 (p < 0.0001), were determined throughout the observed period of time. Patients with initially poor graft function revealed higher trough levels (n = 24; 20.1 ± 11.6ng/mL) in comparison with fair (n = 40; 13.7 ± 7.8 ng/mL) and good function (n = 29; 9.5 ± 4.4ng/mL; p < 0.0001) already at the second post-transplant day. Toxic levels could be predicted with an area under receiver operating characteristic analysis AUROC=0.751 (p = 0.001) with high sensitivity and specificity. Insufficient levels could be predicted with AUROC=0.800 (p = 0.003). In conclusion, initial graft function is a major factor influencing the pharmacokinetics of tacrolimus and can be validly determined by the LiMAx test. Thus, recipients with poor functioning grafts are prone of developing toxic levels within the first week after LT, whereas patients with good functioning grafts frequently develop insufficient levels with the current immunosuppressive protocols.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Johan F
authors.initials: JF
authors.lastname: Lock
authors.forename: Maciej
authors.initials: M
authors.lastname: Malinowski
authors.forename: Eugen
authors.initials: E
authors.lastname: Schwabauer
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer
authors.forename: Gero
authors.initials: G
authors.lastname: Puhl
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Martin
authors.initials: M
authors.lastname: Stockmann
mesh_terms: D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008107:Liver Diseases / Q000601:surgery*; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus