title: Differences in the incidence and clinical evolution of early neurotoxicity after liver transplantation based on tacrolimus formulation used in the immunosuppressive induction protocol.
abstract: BACKGROUND
  Posttransplant early calcineurin inhibitor (CNI)-induced neurotoxicity (ECIIN) was related to high CNI levels, among other factors. Minimizing exposure could modify its incidence or clinical evolution.
  
  
  OBJECTIVE
  To compare the incidence, predisposing factors, and clinical evolution of ECIIN after immunosuppressive induction with low-dose tacrolimus-MR (Advagraf) or conventional dose tacrolimus (Prograf).
  
  
  METHODS
  We matched 71 patients treated with an immunosuppression induction schedule with basiliximab and low doses of Advagraf (cases group) 1:1 by recipient age and indication for liver transplantation (OLT) with patients treated with a conventional tacrolimus regimen (control group). Baseline characteristics, liver and kidney function, operative technical characteristics, kidney function, and C0 tacrolimus levels at several time points after liver OLT were analyzed.
  
  
  RESULTS
  There were 31 cases of ECIIN (21%), 14 in the cases group (20%) and 17 in the control group (24%; P < .001). The incidence of ECIIN was higher in alcoholic liver disease (odds ratio [OR], 8.2; 95% CI, 2.3-28.6; P < .001) and past history of encephalopathy (OR, 2.6; 95% CI, 1.16-5.9; P < .02). Among cases, the incidence of ECIIN was higher when encephalopathy signs were present at time of transplantation (36% vs 12%; P < .001). Control of ECIIN required a switch to cyclosporine therapy in all those in the cases group, whereas this was only needed for 9 cases in the control group (47%; P < .001).
  
  
  CONCLUSIONS
  In this study, although the incidence rate of neurotoxicity induced by Advagraf was lower than the induced by Prograf, it did not respond to routine treatment and required a significantly higher rate of switch to cyclosporine for its control.
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Souto-Rodríguez
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain. Electronic address: esther.molina.perez@sergas.es.
authors.forename: E
authors.initials: E
authors.lastname: Molina-Pérez
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Castroagudín
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernández Pérez
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Otero-Antón
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Tomé Martínez de Rituerto
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Castro
authors.affiliation: Abdominal Trasplant Unit, Universitary Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Varo-Pérez
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000077552:Basiliximab; D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D000911:Antibodies, Monoclonal; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D016559:Tacrolimus