title: Early withdrawal of cyclosporine A improves 1-year kidney graft structure and function in sirolimus-treated patients.
abstract: BACKGROUND
  Chronic allograft nephropathy (CAN) represents the most common cause of late graft loss. Nephrotoxicity from chronic use of calcineurin inhibitors (CNI) has the potential to contribute to CAN. The present investigation aimed to evaluate the impact of early CNI withdrawal on kidney graft function and structure at 1 year in sirolimus (SRL)-treated patients.
  
  
  METHODS
  Forty consecutive kidney transplant recipients were initially treated with corticosteroids, cyclosporine A (CsA), and SRL (2 mg/day). After 3 months, patients were randomly assigned to either continue the same treatment (group I) or to withdraw CsA and continue SRL (group II). All patients underwent kidney graft biopsy immediately after graft reperfusion (0-hr biopsy) and 12 months after engraftment.
  
  
  RESULTS
  Baseline graft biopsy showed a higher degree of renal damage in group II patients (total score, 4+/-1.6 vs. 2+/-0.9; P<0.05). Twelve months after engraftment, CAN was diagnosed in 55% of all patients, of whom 64% were in group I and 36% in group II. CAN lesions were scored as moderate to severe in 90% of group I patients but only 32% of group II patients (P<0.05). A vascular score greater than or equal to 2 occurred in 90% of group I patients and in 38% of group II patients (P<0.05). At 1 year, group I patients showed a significantly worse kidney graft function (serum creatinine, 2.0+/-0.3 vs. 1.3+/-0.3 mg/dL; creatinine clearance, 54+/-14 vs. 66+/-17 mL/min; both P<0.002).
  
  
  CONCLUSIONS
  These results suggest that early withdrawal of CsA is a safe option, which allows a significant reduction of chronic histologic damage, particularly vascular injury, of cadaveric kidney allografts.
authors.affiliation: Department of Emergency and Organ Transplant, Division of Nephrology, University of Bari, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stallone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.forename: Antonio
authors.initials: A
authors.lastname: Schena
authors.forename: Barbara
authors.initials: B
authors.lastname: Infante
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus