title: HLA mismatches remain risk factors for acute kidney allograft rejection in patients receiving quadruple immunosuppression with anti-interleukin-2 receptor antibodies.
abstract: BACKGROUND
  New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned.
  
  
  METHODS
  We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling.
  
  
  RESULTS
  Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation.
  
  
  CONCLUSIONS
  Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.
authors.affiliation: Department of Nephrology and Renal Transplantation, ULB Hopital Erasme, Brussels, Belgium. wissing@ulb.ac.be
authors.forename: Karl M
authors.initials: KM
authors.lastname: Wissing
authors.forename: Guy
authors.initials: G
authors.lastname: Fomegné
authors.forename: Nilufer
authors.initials: N
authors.lastname: Broeders
authors.forename: Lidia
authors.initials: L
authors.lastname: Ghisdal
authors.forename: Anh Dung
authors.initials: AD
authors.lastname: Hoang
authors.forename: Dimitri
authors.initials: D
authors.lastname: Mikhalski
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: D000208:Acute Disease; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2