title: WOFIE synergizes with calcineurin-inhibitor treatment and early steroid withdrawal in kidney transplantation.
abstract: BACKGROUND
  According to the window of opportunity for immunologic engagement (WOFIE) concept, as designed by R. Calne, the authors prospectively analyzed the effect of a 72-hr immunosuppressive window on graft function in renal transplant recipients.
  
  
  METHODS
  Immunosuppressive therapy comprised tacrolimus (trough levels, 5-8 ng/mL after day 8 posttransplantation), daclizumab (1 mg/kg body weight at day 0 and 2, 4, 6, and 8 weeks posttransplantation), mycophenolate mofetil (MMF) (1-2 g/day), and prednisolone. All patients received an induction therapy including daclizumab, prednisolone, and MMF. WOFIE patients were stopped from immunosuppression for 72 hr posttransplant. Steroids were withdrawn in both groups 12 to 16 weeks after transplantation and dual therapy with MMF and low-dose tacrolimus ensued.
  
  
  RESULTS
  Thirty renal transplant recipients (16 in the WOFIE group and 14 in the control group) have been enrolled since May 2000. Patient and graft survival were 93.8% and 87.5%, respectively, in the WOFIE group and 100.0% and 92.9% in the control group, respectively. One patient in the WOFIE group died of cytomegalovirus infection with stable graft function. There were no grafts lost because of acute rejection or primary nonfunction in either group. Patients treated according to the WOFIE protocol revealed less acute rejection episodes during the time of observation (first biopsy-confirmed acute rejection rate 12.5% in the WOFIE group vs. 42.9% in the control cohort). Whereas 92.1% of the WOFIE patients were successfully discontinued from steroids, permanent steroid withdrawal was achieved in only 60% of the control cohort.
  
  
  CONCLUSIONS
  Initial interruption of immunosuppression was associated with a decrease of acute graft rejections. Subsequently, the authors postulate a synergistic effect on the immunosuppressive efficiency of calcineurin inhibitors when combined with an initial drug-free window.
authors.affiliation: Department of General and Thoracic Surgery, University of Kiel, Kiel, Germany. dresske@t-online.de.
authors.forename: Bettina
authors.initials: B
authors.lastname: Dresske
authors.forename: Nicholas
authors.initials: N
authors.lastname: Zavazava
authors.forename: Stefan
authors.initials: S
authors.lastname: Jenisch
authors.forename: Beate
authors.initials: B
authors.lastname: Exner
authors.forename: Philine
authors.initials: P
authors.lastname: Lenz
authors.forename: Nour Eddine
authors.initials: NE
authors.lastname: El Mokhtari
authors.forename: Bernd
authors.initials: B
authors.lastname: Kremer
authors.forename: Fred
authors.initials: F
authors.lastname: Faendrich
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D000077561:Daclizumab; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage*; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011239:Prednisolone; D000077561:Daclizumab; D016559:Tacrolimus