title: Long-term outcome of very early cyclosporine minimization and de novo everolimus therapy in kidney transplant recipients: a pharmacokinetic guided approach.
abstract: BACKGROUND
  Cyclosporine (CsA) nephrotoxicity is an important cause of chronic allograft dysfunction. Clinical information concerning the impact of very early CsA dose reduction in kidney transplant recipients is limited. We have examined the long-term outcomes of very early CsA dose reduction. This is synchronized with de novo everolimus and steroid therapy.
  
  
  METHODS
  We enrolled 10 de novo kidney transplant recipients to receive CsA (target C(0) 250-350 ng/mL) and prednisolone as initial therapy. CsA dosage was reduced by 50% at posttransplant day 7. Everolimus (target trough level, 3-8 ng/mL) was concomitantly started at the day of CsA reduction. Full pharmacokinetic studies of everolimus and CsA were studied at the period of 4-8 weeks after CsA reduction. CsA was then gradually reduced to maintain a trough level of 50-100 ng/mL and/or C(max) <600 ng/mL.
  
  
  RESULTS
  The mean follow-up was 51.2 ± 3.45 months. The nadir serum creatinine was 1.03 ± 0.33 mg/dL. The mean initial estimated glomerular filtration rate (eGFR) was 97.97 ± 23.36 mL/min. The mean initial trough everolimus was 5.2 ± 1.5 ng/mL. The eGFR at 1 year, 3 years, and last follow-up was 82 ± 25, 80 ± 21, and 80 ± 25 mL/min, respectively. Patient and graft survival was 100%.
  
  
  CONCLUSIONS
  Very early CsA dose reduction synchronized with de novo everolimus therapy was associated with good long-term patient and graft survival in kidney transplant recipients. This intervention can lead to 75% CsA minimization and is associated with very good GFR by the modification of Diet in Renal Disease Formula at year 4.
authors.affiliation: Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. ravsm@mahidol.ac.th
authors.forename: V
authors.initials: V
authors.lastname: Sumethkul
authors.forename: P
authors.initials: P
authors.lastname: Tankee
authors.forename: P
authors.initials: P
authors.lastname: Chalermsanyakorn
authors.forename: S
authors.initials: S
authors.lastname: Jirasiritham
mesh_terms: D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D020123:Sirolimus