title: Effects of immediate switch from cyclosporine microemulsion to tacrolimus at first acute rejection in renal allograft recipients.
abstract: BACKGROUND
  A number of institutions have reported favorable results in renal transplant patients after conversion from cyclosporine (CsA) to tacrolimus at the time of acute rejection, but no prospective, controlled study has been performed to date. Here, we report the first randomized study comparing patients whose therapy was changed at a first episode of acute rejection to tacrolimus with those who were maintained on CsA microemulsion (ME).
  
  
  METHODS
  This 3-month, prospective, open, multicenter, parallel-group study was conducted at 15 centers in seven European countries. In total, 119 renal graft recipients experiencing a first biopsy-proven acute rejection episode while receiving CsA-ME were randomized (1:1) to start tacrolimus-based therapy (n=61) or to continue CsA-ME-based therapy (n=58).
  
  
  RESULTS
  Baseline characteristics were comparable for both groups. The initial rejection episode responded to steroid treatment in 93.4% (tacrolimus) and 63.8% (CsA-ME) (P=0.001), respectively. In patients at risk, the incidence of recurrent rejection events within 3 months was significantly lower with tacrolimus therapy (5/57, 8.8%) compared with CsA-ME therapy (15/44, 34.1%) (P=0.002). Patient and graft survival were similar in both study groups 3 months after randomization. The most frequently reported adverse events were increased serum creatinine (29.5% vs. 22.4%), hypertension (24.6% vs. 22.4%), and urinary tract infection (18.0% vs. 20.7%) for tacrolimus versus CsA-ME. Tremor was more common in tacrolimus treated-patients (17.4% vs. 2.1%, P=0.011).
  
  
  CONCLUSIONS
  Early conversion to tacrolimus therapy benefited the resolution of acute rejection episodes and significantly reduced the risk of recurrent rejection compared with continuation of CsA-ME.
authors.affiliation: The Renal Unit, Western Infirmary, Glasgow, Scotland, UK. douglas.briggs@ukgateway.net
authors.forename: Douglas
authors.initials: D
authors.lastname: Briggs
authors.forename: Chris
authors.initials: C
authors.lastname: Dudley
authors.forename: James
authors.initials: J
authors.lastname: Pattison
authors.forename: Per
authors.initials: P
authors.lastname: Pfeffer
authors.forename: Kaija
authors.initials: K
authors.lastname: Salmela
authors.forename: Peter
authors.initials: P
authors.lastname: Rowe
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tydén
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004655:Emulsions; D005060:Europe; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D004655:Emulsions; D016572:Cyclosporine; D016559:Tacrolimus