title: Rejection after simultaneous pancreas-kidney transplantation.
abstract: BACKGROUND
  Simultaneous pancreas-kidney (SPK) transplantation is an accepted therapy for type 1 diabetic patients with end-stage renal disease. This study analyses the occurrence of rejection episodes in patients undergoing SPK.
  
  
  METHODS
  The study population was obtained from 205 patients enrolled in the Euro-SPK 001 study and randomized to receive tacrolimus- (n = 103) or cyclosporin microemulsion (ME)-based (n = 102) immunosuppressive therapy. All patients received concomitant antibody induction therapy, mycophenolate mofetil and short-term corticosteroids.
  
  
  RESULTS
  After 3 years of follow-up, rejection episodes occurred in 41 patients receiving tacrolimus and in 51 patients receiving cyclosporin-ME. The majority of first rejection episodes in both groups occurred during the first 6 months (93 and 90%, respectively) and in most cases were treated with corticosteroids alone (88 vs 90%). Actuarial rejection-free kidney and/or pancreas graft survival was similar for tacrolimus (54%) and cyclosporin-ME (44%). Human leukocyte antigen (HLA) compatibility (P = 0.003) and graft vessel extension (P = 0.000001) had a significant influence on rejection-free graft survival. Also, rejection influenced pancreas graft survival (P = 0.01), and pancreas graft loss due to rejection influenced patient survival (P = 0.02). In the intent-to-treat analysis of early rejection, significantly fewer tacrolimus- than cyclosporin-ME-treated patients had (i) more than one rejection episode (11 out of 40 vs 24 out of 47; P = 0.03); (ii) first moderate to severe rejection (one out of 40 vs 12 out of 47; P = 0.004); and (iii) refractory rejection (two out of 40 vs 10 out of 47; P = 0.03). Pancreas survival was lower in late rejectors (53%) than non-rejectors (86%; P = 0.002). Also, serum creatinine was highest in late rejectors.
  
  
  CONCLUSIONS
  Tacrolimus-based immunosuppressive therapy demonstrates significant advantages over cyclosporin-ME in terms of the severity of acute rejection in SPK transplant patients.
authors.affiliation: Department of Surgery, University of Munich, Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany. helmut.arbogast@med.uni-muenchen.de
authors.forename: Helmut
authors.initials: H
authors.lastname: Arbogast
authors.forename: Jacques
authors.initials: J
authors.lastname: Malaise
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Illner
authors.forename: Anwar
authors.initials: A
authors.lastname: Tarabichi
authors.forename: Christoph
authors.initials: C
authors.lastname: Dieterle
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Landgraf
authors.forename: Walter
authors.initials: W
authors.lastname: Land
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000150:complications / Q000601:surgery; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011183:Postoperative Complications; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus