title: Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression.
abstract: BACKGROUND
  The aim of our study was to examine, in a recent cohort of kidney transplant recipients who have received modern immunosuppressive therapy, the respective role of cold ischemia time (CIT) and delayed graft function (DGF) on acute rejection (AR) rates and long-term graft survival.
  
  
  METHODS
  We retrospectively reviewed the charts of 611 renal transplantations between 1996 and 2005. Most patients received a calcineurin inhibitor as maintenance therapy, either cyclosporine (43%) or tacrolimus (52%) and 76% of the patients received an antilymphocyte induction therapy. Study endpoints were DGF, first-year AR, and long-term graft survival. Uni- and multivariate analyses were performed to determine factors that may have influenced the study outcomes.
  
  
  RESULTS
  DGF was observed in 16.2% of patients. Both older donor age and longer CIT were significant risk factors for DGF. DGF rates were similar whether patients received a calcineurin inhibitor before transplantation or not. AR occurred in 16.5% of grafts during the first year. Independent predictors of AR by multivariate analysis were duration of dialysis, CIT, current panel-reactive lymphocytotoxic antibody more than 5%, and the number of human leukocyte antigen-A, B, and DR mismatches. Each hour of cold ischemia increases the risk of rejection by 4%. With respect to death-censored graft survival, three pretransplant parameters emerged as independent predictors of graft loss: younger recipient age, peak panel-reactive lymphocytotoxic antibody more than 5% and longer CIT. The detrimental effect of CIT on graft survival was entirely because of its propensity to trigger AR. When AR was added to the multivariate Cox model, CIT was no longer significant whereas first-year AR became the most important predictor of graft loss (Hazards ratio, 4.6).
  
  
  CONCLUSIONS
  Shortening CIT will help to decrease not only DGF rates but also AR incidence and hence graft loss. Patients with prolonged CIT should receive adequate immunosuppression, possibly with antilymphocyte preparations, to prevent AR occurrence.
authors.affiliation: Department of Digestive surgery and Transplantation, CUB Hopital Erasme, Brussels, Belgium.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Mikhalski
authors.forename: Karl Martin
authors.initials: KM
authors.lastname: Wissing
authors.forename: Lidia
authors.initials: L
authors.lastname: Ghisdal
authors.forename: Nilufer
authors.initials: N
authors.lastname: Broeders
authors.forename: Marie
authors.initials: M
authors.lastname: Touly
authors.forename: Anh-Dung
authors.initials: AD
authors.lastname: Hoang
authors.forename: Patricia
authors.initials: P
authors.lastname: Loi
authors.forename: Freddy
authors.initials: F
authors.lastname: Mboti
authors.forename: Vincent
authors.initials: V
authors.lastname: Donckier
authors.forename: Pierre
authors.initials: P
authors.lastname: Vereerstraeten
authors.forename: Daniel
authors.initials: D
authors.lastname: Abramowicz
mesh_terms: D000328:Adult; D015331:Cohort Studies; D050377:Cold Ischemia / Q000379:methods*; D016572:Cyclosporine / Q000627:therapeutic use; D051799:Delayed Graft Function / Q000503:physiopathology; D005260:Female; D006084:Graft Rejection / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus