title: Efficacy and safety of de novo or early everolimus with low cyclosporine in deceased-donor kidney transplant recipients at specified risk of delayed graft function: 12-month results of a randomized, multicenter trial.
abstract: Immediate or early use of proliferation signal inhibitor (PSI)/mammalian target of rapamycin (mTOR) inhibitor therapy can avoid high exposure to calcineurin inhibitors but concerns exist relating to the risk of delayed graft function (DGF) and impaired wound healing with the mTOR sirolimus. CALLISTO was a 12-month, prospective, multicenter, open-label study. Deceased-donor kidney transplant patients at protocol-specified risk of DGF were randomized to start everolimus on day 1 (immediate everolimus, IE; n = 65) or week 5 (delayed everolimus, DE; n = 74). Incidence of the primary endpoint (biopsy-proven acute rejection, BPAR; graft loss, death, DGF, wound healing complications related to transplant surgery or loss to follow-up) was 64.6% and 66.2% in the IE and DE groups, respectively, at month 12 (P = 0.860). The overall incidence of BPAR was 20.1%. Median estimated glomerular filtration rate was 48 ml/min/1.73 m(2) and 49 ml/min/1.73 m(2) in the IE and DE groups, respectively, at month 12. DGF and wound healing complications were similar between groups. Adverse events led to study drug discontinuation in 17 IE patients (26.2%) and 28 DE patients (37.8%) (NS). In conclusion, introduction of everolimus immediately or early posttransplant in DGF-risk patients is associated with good efficacy, renal function and safety profile. There seems no benefit in delaying initiation of everolimus.
authors.affiliation: Service de Néphrologie et Transplantation Rénale, Hôpital Hôtel Dieu, Nantes, France. jacques.dantal@chu-nantes.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
authors.forename: François
authors.initials: F
authors.lastname: Berthoux
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Moal
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Robert
authors.initials: R
authors.lastname: Genin
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rerolle
authors.forename: François
authors.initials: F
authors.lastname: Bayle
authors.forename: Pierre François
authors.initials: PF
authors.lastname: Westeel
authors.forename: Denis
authors.initials: D
authors.lastname: Glotz
authors.forename: Niloufar
authors.initials: N
authors.lastname: Kossari
authors.forename: Nicole
authors.initials: N
authors.lastname: Lefrançois
authors.forename: Bernard
authors.initials: B
authors.lastname: Charpentier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Quéré
authors.forename: Fabienne
authors.initials: F
authors.lastname: Di Giambattista
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Cassuto
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus