title: Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation.
abstract: This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.
authors.affiliation: Children's Hospital of Eastern Ontario, University of Ottawa, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Trompeter
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
authors.forename: Alan R
authors.initials: AR
authors.lastname: Watson
authors.forename: David V
authors.initials: DV
authors.lastname: Milford
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tyden
authors.forename: Ryszard
authors.initials: R
authors.lastname: Grenda
authors.forename: Jan
authors.initials: J
authors.lastname: Janda
authors.forename: David
authors.initials: D
authors.lastname: Hughes
authors.forename: Jochen H H
authors.initials: JH
authors.lastname: Ehrich
authors.forename: Bernd
authors.initials: B
authors.lastname: Klare
authors.forename: Graziella
authors.initials: G
authors.lastname: Zacchello
authors.forename: Inge
authors.initials: I
authors.lastname: Bjorn Brekke
authors.forename: Mary
authors.initials: M
authors.lastname: McGraw
authors.forename: Ferenc
authors.initials: F
authors.lastname: Perner
authors.forename: Lucian
authors.initials: L
authors.lastname: Ghio
authors.forename: Egon
authors.initials: E
authors.lastname: Balzar
authors.forename: Styrbjörn
authors.initials: S
authors.lastname: Friman
authors.forename: Rosanna
authors.initials: R
authors.lastname: Gusmano
authors.forename: Jochen
authors.initials: J
authors.lastname: Stolpe
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus