title: How long should initiation of calcineurin inhibitors be delayed to protect renal function in liver transplantation?
abstract: OBJECTIVE
  Delayed introduction of calcineurin inhibitors (CNI) in liver transplantation (OLT) seeks to protect renal function, although the optimal length of the delay is not well established. The aim of this study was to analyze the effects on renal function of CNI initiation on different days after OLT.
  
  
  METHODS
  We reviewed the charts of 260 OLT recipients. Group D1-a (n = 36) underwent the standard initial immunosuppression at our center: namely, CNI introduction on day 1 with further daily administration to achieve target levels of 8 to 15 ng/mL for tacrolimus or 150 to 300 ng/mL for cyclosporine. Due to renal concerns, 126 patients (group D1-b) had CNI introduced on day 1 either not daily or at doses to achieve less than the target on at least two occasions. In 43 patients (group D2), CNI were introduced on day 2 in 23 on day 3 (group D3), in 12 on day 4 (group D4), and at least at day 5 in 20 others (group D5). In periods without CNI treatment, patients received mycophenolate mofetil. Steroids were administered to all patients. The study period included the first 3 months post-OLT. Renal function was estimated as creatinine clearance (CrCl) using the Cockcroft-Gault equation.
  
  
  RESULTS
  Changes in CrCl from pre-OLT to month 3 were -19% ± 28% in group D1-a; -27% ± 19% in group D1-b; -29% ± 19% in group D2; -23% ± 26% in group D3; -4% ± 38% in group D4, and +4% ± 33% in group D5 (P < .05 vs groups D1-a, D1-b, D2, and D3). On multivariate analysis, CNI introduction at day ≥ 5 was protective for kidneys when adjusted for other variables that potentially influence renal function.
  
  
  CONCLUSIONS
  CNI should be introduced at day 5 after OLT to protect renal function.
authors.affiliation: Hospital Clinic, IDIBAPS, CIBEREHD, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rafael-Valdivia
authors.forename: M A
authors.initials: MA
authors.lastname: Mendoza
authors.forename: B
authors.initials: B
authors.lastname: Martinez-Saldivar
authors.forename: A
authors.initials: A
authors.lastname: Sanchez-Fueyo
authors.forename: M
authors.initials: M
authors.lastname: Brunet
authors.forename: J C
authors.initials: JC
authors.lastname: Garcia-Valdecasas
authors.forename: A
authors.initials: A
authors.lastname: Rimola
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D016031:Liver Transplantation; D008297:Male; D008485:Medical Audit; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus