title: Efficacy and safety outcomes among de novo renal transplant recipients managed by C2 monitoring of cyclosporine a microemulsion: results of a 12-month, randomized, multicenter study.
abstract: BACKGROUND
  The clinical benefits of C2 monitoring of cyclosporine microemulsion have been demonstrated, but C2 targets in renal transplant recipients during the first year require validation.
  
  
  METHODS
  MO2ART was a prospective, multicenter study of renal transplant recipients managed by C2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine. Patients were randomized on day 3 to two groups, which were managed from month 3 with higher or lower C2 target ranges (months 4-6, 1,000-1,200 ng/mL vs. 800-1,000 ng/mL; months 7-12, 800-1,000 ng/mL vs. 600-800 ng/mL, respectively). The primary endpoint was the glomerular filtration rate (GFR) at month 12.
  
  
  RESULTS
  A total of 296 patients were recruited, of whom 250 remained in the study at 3 months (higher-C2, n=131; lower-C2, n=119). GFR at 12 months did not differ between the higher- and lower-C2 groups (65+/-17 mL/min vs. 66+/-14 mL/min). When patients were regrouped according to C2 achieved by months 8 to 12, those with the lowest C2 (<700 ng/mL) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 (P=0.04). Five episodes of biopsy-proven acute rejection occurred after month 3 (higher-C2 group, n=2; lower-C2 group, n=3). The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7%. Patient and graft survival were 93% and 89%, respectively, at 12 months.
  
  
  CONCLUSIONS
  Both C2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months. The decision to target the higher or lower end of these C2 ranges should be made on an individual basis, taking into account patient and graft characteristics, and co-medication.
authors.affiliation: Institute of Nephrology, Dialysis and Renal Transplantation, S. Orsola University Hospital, Bologna, Italy. sergio.stefoni@unibo.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Stefoni
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtved
authors.forename: Edward
authors.initials: E
authors.lastname: Cole
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.forename: Sandra
authors.initials: S
authors.lastname: Cockfield
authors.forename: Matthias
authors.initials: M
authors.lastname: Buchler
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Toselli
authors.forename: Luis M
authors.initials: LM
authors.lastname: Pallardo
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
authors.forename: Helen
authors.initials: H
authors.lastname: Pilmore
authors.forename: Michèle
authors.initials: M
authors.lastname: Kessler
authors.forename: Steve
authors.initials: S
authors.lastname: Chadban
authors.forename: César Agost
authors.initials: CA
authors.lastname: Carreño
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D016903:Drug Monitoring; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine