title: Reduced-exposure cyclosporine is safe and efficacious in de novo renal transplant recipients treated with enteric-coated mycophenolic acid and basiliximab.
abstract: BACKGROUND
  The lower limit of exposure to calcineurin inhibitors has not yet been established in de novo renal transplant patients receiving mycophenolic acid therapy with basiliximab.
  
  
  METHODS
  A 12-month, multicenter, randomized, open-label trial was carried out in which de novo renal transplant patients received enteric-coated mycophenolate sodium, cyclosporine microemulsion, steroids and basiliximab. Patients were randomized to receive standard-exposure (n = 45) or reduced-exposure (n = 44) cyclosporine, based on differing C2 target ranges, after the first month post-transplant.
  
  
  RESULTS
  Cyclosporine exposure gradually increased over the first month and was lower than previously recommended. Mean calculated creatinine clearance (primary end-point) was similar in the standard-exposure and reduced-exposure groups at month 6 (55.3+/-3.2 ml/min and 61.5+/-3.7 ml/min respectively, n.s.). There were 4 deaths but no death-censored graft losses, resulting in 95.5% patient and graft survival at one year in both groups. At 6 and 12 months, the incidence of biopsy-proven acute rejection was 17.8% and 17.8% in the standard-exposure group, and 13.6% and 15.9% in the reduced-exposure group. Adverse events were similar between treatment groups. Exploratory analyses could not identify a lower limit for the optimal CsA exposure range, but results suggested that high exposure at one year was associated with deteriorating renal function.
  
  
  CONCLUSIONS
  These results indicate that enteric-coated mycophenolate sodium with reduced-exposure cyclosporine, steroids and basiliximab induction has an excellent therapeutic effect and is safe in de novo kidney transplant recipients. Lower C2 targets than previously recommended, particularly early post-transplant, do not appear to be associated with compromised efficacy.
authors: Department of Nephrology, Campus Charité Mitte Charité, Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany. klemens.budde@charite.de
authors: K
authors: K
authors: Budde
authors: J L
authors: JL
authors: Bosmans
authors: J
authors: J
authors: Sennesael
authors: M
authors: M
authors: Zeier
authors: P
authors: P
authors: Pisarski
authors: M
authors: M
authors: Schütz
authors: W
authors: W
authors: Fischer
authors: H H
authors: HH
authors: Neumayer
authors: P
authors: P
authors: Glander
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D000077552:Basiliximab; D001530:Belgium / Q000453:epidemiology; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004655:Emulsions; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D015996:Survival Rate; D013608:Tablets, Enteric-Coated; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D004655:Emulsions; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; D000077552:Basiliximab; D003404:Creatinine; D009173:Mycophenolic Acid