title: Immunosuppression Modification by Everolimus With Minimization of Calcineurin Inhibitors Recovers Kidney Graft Function Even in Patients With Very Late Conversion and Also With Poor Graft Function.
abstract: BACKGROUND
  Although kidney graft survival within 5 years after transplantation is now achieved in >95% of recipients, chronic graft deterioration remains a factor limiting long-term survival. Chronic nephrotoxicity induced by calcineurin inhibitors (CNIs) is one of the major causes of chronic graft injury; thus, minimization of CNIs by administration of everolimus (EVR) is expected to relieve their toxic effects.
  
  
  METHODS
  Fifty-six kidney transplant recipients receiving CNI-based immunosuppression (tacrolimus, n = 34; cyclosporine, n = 22) were analyzed. The average posttransplant period at conversion was 7.4 years and no less than 3 years. Conversion of immunosuppression was accomplished by reducing CNI by 40% in dose and beginning EVR at 1 or 1.5 mg. Changes in graft function were examined, and adverse effects were evaluated.
  
  
  RESULTS
  Significant improvement in graft function was observed quickly after EVR administration, and it had persisted for 1 year after conversion as a 7% increase in estimated glomerular filtration rate. No obvious acute rejection was observed. Further analyses concerning "timing of EVR conversion" and "graft function at conversion" were performed. Graft function was significantly improved even in patients with late conversion at 2 to 10 years. The estimated glomerular filtration rate was significantly improved even in patients with poor function.
  
  
  CONCLUSIONS
  We concluded that this modification to the immunosuppressive regimen, as expected, reduced CNI nephrotoxicity. Our results showed that even patients with very late conversion or poor graft function also benefited from EVR conversion with CNI minimization.
authors.affiliation: Kidney Transplant Center and Department of Urology, Hyogo College of Medicine, Hyogo, Japan. Electronic address: nojimam@hyo-med.ac.jp.
authors.forename: M
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Kidney Transplant Center and Department of Urology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Urology, Chibune General Hospital, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Urology, Meiwa Hospital, Hyogo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shimatani
authors.affiliation: Kidney Transplant Center and Department of Urology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kanematsu
authors.affiliation: Kidney Transplant Center and Department of Urology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000008:administration & dosage*; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D019737:Transplants / Q000187:drug effects; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D016559:Tacrolimus