title: Excellent long-term results in de novo renal transplant recipients treated with proliferation signal inhibitors and reduced calcineurin inhibitors exposure.
abstract: BACKGROUND
  A new class of immunosuppressants, proliferation signal inhibitors (PSI)--sirolimus and everolimus--has the potential to prevent chronic allograft nephropathy (CAN). This retrospective analysis reports a 6-year practice using PSI at a single center, comparing a regimen based on reduced-dose calcineurin inhibitors (CNI) and PSI versus full-dose CNI and mycophenolic acid (MPA).
  
  
  METHODS
  The study population included 70 patients (group A) who received de novo PSI therapy in combination with reduced dose of CNI, standard steroids, and basiliximab induction, and 216 patients (group B) with full-dose CNI, MPA, steroids, and basiliximab induction.
  
  
  RESULTS
  No statistically significant differences were recorded in the baseline donor and recipient characteristics. A difference was observed in cold ischemia time, which could represent a bias for the analysis. No differences were recorded in actuarial patient survival, delayed graft function, biopsy-proven acute rejection rates, and renal function analysis. A significant difference was recorded in the actuarial graft survival rate at years 2, 3, and 4 (P< .01), as well as overall graft survival rates (P= .025).
  
  
  CONCLUSIONS
  The reduction of cold preservation time seemed to be an important factor to improve both short- and long-term renal function. This regimen revealed a long-term trend toward better renal function and graft survival. The use of PSI with reduced doses of CNI seems to be indicated for suboptimal grafts, especially when a reduced quality of the kidney is associated with prolonged cold ischemia time.
authors.affiliation: Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy. carmellini@unisi.it
authors.forename: M
authors.initials: M
authors.lastname: Carmellini
authors.forename: A
authors.initials: A
authors.lastname: Collini
authors.forename: G
authors.initials: G
authors.lastname: Ruggieri
authors.forename: G
authors.initials: G
authors.lastname: Garosi
authors.forename: M
authors.initials: M
authors.lastname: Bernini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000145:classification / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012189:Retrospective Studies; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus