title: Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF-four-year results of the Postconcept study.
abstract: Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months. Renal function (Cockcroft and Gault) was significantly better at month 48 (M48) in the SRL group both in the intent-to-treat population (ITT): 62.6 mL/min/1.73 m(2) versus 57.1 mL/min/1.73 m(2) (p = 0.013) and in the on-treatment population (OT): 67.5 mL/min/1.73 m(2) versus 57.4 mL/min/1.73 m(2) (p = 0.002). Two biopsy proven acute rejection episodes occurred after M12 in each group. Graft and patient survival were comparable (graft survival: 97.4 vs. 100%; patient survival: 97.4 vs. 97.6%, respectively). The incidence of new-onset diabetes was numerically increased in the SRL group (7 vs. 2). In OT, three cancers occurred in the SRL group versus nine in the CsA group and mean proteinuria was increased in the SRL group (0.42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation.
authors.affiliation: Department of Nephrology, Clinical Immunology, University Hospital, François Rabelais University, Tours, France. lebranchu@med.univ-tours.fr
authors.forename: Y
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: A
authors.initials: A
authors.lastname: Thierry
authors.forename: E
authors.initials: E
authors.lastname: Thervet
authors.forename: M
authors.initials: M
authors.lastname: Büchler
authors.forename: I
authors.initials: I
authors.lastname: Etienne
authors.forename: P F
authors.initials: PF
authors.lastname: Westeel
authors.forename: B
authors.initials: B
authors.lastname: Hurault de Ligny
authors.forename: B
authors.initials: B
authors.lastname: Moulin
authors.forename: J P
authors.initials: JP
authors.lastname: Rérolle
authors.forename: T
authors.initials: T
authors.lastname: Frouget
authors.forename: S
authors.initials: S
authors.lastname: Girardot-Seguin
authors.forename: O
authors.initials: O
authors.lastname: Toupance
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus