title: Mycophenolate mofetil decreases rejection in simultaneous pancreas-kidney transplantation when combined with tacrolimus or cyclosporine.
abstract: BACKGROUND
  Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two "state-of-the-art" immunosuppression regimens in a prospective, randomized, single-center study.
  
  
  METHODS
  Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neoral formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5 mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgbA1C, hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sandimmune formulation) and AZA-based immunosuppression.
  
  
  RESULTS
  The incidence of biopsy-proven acute rejection was 11% in both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (HgbA1C, hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC to CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patients in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation.
  
  
  CONCLUSIONS
  The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.
authors.affiliation: Department of Surgery, University of Colorado School of Medicine, Denver 80262, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Stegall
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: M E
authors.initials: ME
authors.lastname: Wachs
authors.forename: L
authors.initials: L
authors.lastname: Chan
authors.forename: C
authors.initials: C
authors.lastname: Nolan
authors.forename: I
authors.initials: I
authors.lastname: Kam
mesh_terms: D000328:Adult; D000368:Aged; D003365:Costs and Cost Analysis; D003401:Creatine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000191:economics / Q000379:methods*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016035:Pancreas Transplantation / Q000379:methods*; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D016853:Muromonab-CD3; D016572:Cyclosporine; D009173:Mycophenolic Acid; D003401:Creatine; D016559:Tacrolimus