title: Everolimus with very low-exposure cyclosporine a in de novo kidney transplantation: a multicenter, randomized, controlled trial.
abstract: BACKGROUND
  In combination with everolimus (EVL), cyclosporine A (CsA) may be used at low exposure, so reducing the risk of renal dysfunction in renal transplant recipients (RTR). We evaluated whether higher exposure of EVL could allow a further reduction of CsA.
  
  
  METHODS
  De novo RTR were randomized to standard exposure EVL (C0 3-8 ng/mL) with low-concentration CsA (C2 maintenance levels 350-500 ng/mL, group A) or higher EVL exposure (C0 8-12 ng/mL) with very low-concentration CsA (C2 maintenance levels 150-300 ng/mL, group B). The primary endpoints were 6-month creatinine clearance (CrCl) and biopsy-proven acute rejection (BPAR) rate. After 6 months, patients were followed up (observational extension) to 12 months.
  
  
  RESULTS
  Two hundred eighty-five RTR (97% from deceased donors) were enrolled. Two patients per group died (1.4%). The 6-month death-censored graft survival was 90.2% in group A and 97.9% in group B and was unchanged at 12 months (P=0.007). There was no significant difference between groups at 6 months in CrCl (59.9 vs. 57.8 mL/min) and BPAR rates (14.7% vs. 11.9%) and also at 12 months (CrCl 62.5+/-20.7 vs. 61.3+/-22.0 mL/min, BPAR 14.7% vs. 14.1%). No significant differences were seen in treated acute rejections, steroid-resistant acute rejections, treatment failures, or delayed graft function, although there was a trend to better results in group B.
  
  
  CONCLUSIONS
  EVL given at higher exposure for 6 months plus very low CsA concentration may obtain low acute rejection rate and good graft survival in De novo renal transplantation. However, there was no difference between groups in CrCl.
authors.affiliation: Renal Transplant Unit, Careggi University Hospital, Florence, Italy. salvadorim@aou-careggi.toscana.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Salvadori
authors.forename: Maria Piera
authors.initials: MP
authors.lastname: Scolari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bertoni
authors.forename: Franco
authors.initials: F
authors.lastname: Citterio
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Maria
authors.initials: M
authors.lastname: Cossu
authors.forename: Antonio
authors.initials: A
authors.lastname: Dal Canton
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tisone
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertazzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Pisani
authors.forename: Giampiero
authors.initials: G
authors.lastname: Gubbiotti
authors.forename: Gianbenedetto
authors.initials: G
authors.lastname: Piredda
authors.forename: Ghil
authors.initials: G
authors.lastname: Busnach
authors.forename: Vito
authors.initials: V
authors.lastname: Sparacino
authors.forename: Volker
authors.initials: V
authors.lastname: Goepel
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Messa
authors.forename: Pasquale
authors.initials: P
authors.lastname: Berloco
authors.forename: Domenico
authors.initials: D
authors.lastname: Montanaro
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Veroux
authors.forename: Stefano
authors.initials: S
authors.lastname: Federico
authors.forename: Marta
authors.initials: M
authors.lastname: Bartezaghi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corbetta
authors.forename: Claudio
authors.initials: C
authors.lastname: Ponticelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D019520:Living Donors; D008875:Middle Aged; D010349:Patient Compliance; D018579:Patient Selection; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D020123:Sirolimus