title: Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions.
abstract: BACKGROUND
  Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologic substrate and a reduction in CAN.
  
  
  METHODS
  We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups.
  
  
  RESULTS
  The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05).
  
  
  CONCLUSIONS
  Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome.
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Ruiz
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Dolores
authors.initials: D
authors.lastname: Prats
authors.forename: Jose A
authors.initials: JA
authors.lastname: Gutiérrez
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Henriques
authors.forename: Jose R
authors.initials: JR
authors.lastname: Pinto
authors.forename: Javier
authors.initials: J
authors.lastname: García
authors.forename: Jose M
authors.initials: JM
authors.lastname: Morales
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gómez
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D016572:Cyclosporine; D020123:Sirolimus