title: Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.
abstract: BACKGROUND
  The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients.
  
  
  METHODS
  This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day.
  
  
  RESULTS
  At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction).
  
  
  CONCLUSIONS
  Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.
authors.affiliation: Service de Nephrologie et Transplantation, Hopital Lapeyronie, 371 Av. Du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France.
authors.forename: G
authors.initials: G
authors.lastname: Mourad
authors.forename: V
authors.initials: V
authors.lastname: Garrigue
authors.forename: J P
authors.initials: JP
authors.lastname: Squifflet
authors.forename: T
authors.initials: T
authors.lastname: Besse
authors.forename: F
authors.initials: F
authors.lastname: Berthoux
authors.forename: E
authors.initials: E
authors.lastname: Alamartine
authors.forename: D
authors.initials: D
authors.lastname: Durand
authors.forename: L
authors.initials: L
authors.lastname: Rostaing
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: C
authors.initials: C
authors.lastname: Baron
authors.forename: D
authors.initials: D
authors.lastname: Glotz
authors.forename: C
authors.initials: C
authors.lastname: Antoine
authors.forename: P
authors.initials: P
authors.lastname: Vialtel
authors.forename: T
authors.initials: T
authors.lastname: Romanet
authors.forename: Y
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: A
authors.initials: A
authors.lastname: Al Najjar
authors.forename: C
authors.initials: C
authors.lastname: Hiesse
authors.forename: L
authors.initials: L
authors.lastname: Potaux
authors.forename: P
authors.initials: P
authors.lastname: Merville
authors.forename: J L
authors.initials: JL
authors.lastname: Touraine
authors.forename: N
authors.initials: N
authors.lastname: Lefrancois
authors.forename: M
authors.initials: M
authors.lastname: Kessler
authors.forename: E
authors.initials: E
authors.lastname: Renoult
authors.forename: C
authors.initials: C
authors.lastname: Pouteil-Noble
authors.forename: R
authors.initials: R
authors.lastname: Cahen
authors.forename: C
authors.initials: C
authors.lastname: Legendre
authors.forename: J
authors.initials: J
authors.lastname: Bedrossian
authors.forename: P
authors.initials: P
authors.lastname: Le Pogamp
authors.forename: J
authors.initials: J
authors.lastname: Rivalan
authors.forename: M
authors.initials: M
authors.lastname: Olmer
authors.forename: R
authors.initials: R
authors.lastname: Purgus
authors.forename: F
authors.initials: F
authors.lastname: Mignon
authors.forename: B
authors.initials: B
authors.lastname: Viron
authors.forename: B
authors.initials: B
authors.lastname: Charpentier
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D013256:Steroids; D016559:Tacrolimus