title: Prospective, randomized trial of the effect of antibody induction in simultaneous pancreas and kidney transplantation: three-year results.
abstract: BACKGROUND
  Historically, antibody induction has been used because of the higher immunologic risk of graft loss or rejection observed in simultaneous pancreas and kidney (SPK) transplantation compared with kidney transplantation alone. This trial was designed to assess the effect of antibody induction in SPK transplant recipients receiving tacrolimus, mycophenolate mofetil, and corticosteroids. Induction agents included T-cell-depleting and interleukin-2 receptor antibodies.
  
  
  METHODS
  A total of 174 SPK transplant recipients were enrolled in a prospective, open-label, multi-center study. They were randomized to induction (n=87) or non-induction (n=87) groups and followed for 3 years.
  
  
  RESULTS
  At 3 years, actual patient (94.3% and 89.7%) and pancreas (75.9% and 75.9%) survivals were similar between the induction and non-induction groups, respectively. Actual kidney survival was similar at 1 and 2 years, but at 3 years, it was significantly better in the induction group compared with the non-induction group (92% vs. 81.6%; P =0.04). At 3 years, median serum creatinine and hemoglobin A1C were similar between the induction and non-induction groups (1.35 mg/dL and 1.20 mg/dL, 5.4% and 5.5%, respectively). Three-year cumulative incidence of biopsy-confirmed, treated acute kidney rejection in the induction and non-induction groups was 19.5% and 27.5% (P =0.14), respectively, with odds 4.6 times greater in African Americans regardless of treatment (P =0.004). Significantly higher rates of cytomegalovirus (CMV) viremia and CMV syndrome occurred in those receiving T-cell-depleting antibody induction (36.1%) when compared with those receiving anti-interleukin-2 receptor antibodies (2%) and non-induction (8.1%) (P <0.0001).
  
  
  CONCLUSIONS
  Tacrolimus, mycophenolate mofetil, and corticosteroids resulted in excellent safety and efficacy in SPK transplant recipients. Actual 3-year kidney survival was significantly better in the induction group; however, CMV viremia and CMV syndrome rates were significantly higher in the T-cell-depleting antibody group. African Americans demonstrated a significantly greater risk of acute rejection despite antibody induction. Decisions regarding the use of induction therapy must weigh the risk of kidney graft loss or rejection against the risk of infection.
authors.affiliation: Department of Surgery, University of Miami, Miami, Florida 33136, USA. GBurke@med.miami.edu
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
authors.forename: Dixon B
authors.initials: DB
authors.lastname: Kaufman
authors.forename: J Michael
authors.initials: JM
authors.lastname: Millis
authors.forename: A Osama
authors.initials: AO
authors.lastname: Gaber
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Johnson
authors.forename: David E R
authors.initials: DE
authors.lastname: Sutherland
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Punch
authors.forename: Barry D
authors.initials: BD
authors.lastname: Kahan
authors.forename: Eugene
authors.initials: E
authors.lastname: Schweitzer
authors.forename: Alan
authors.initials: A
authors.lastname: Langnas
authors.forename: James
authors.initials: J
authors.lastname: Perkins
authors.forename: John
authors.initials: J
authors.lastname: Scandling
authors.forename: Waldo
authors.initials: W
authors.lastname: Concepcion
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
authors.forename: James A
authors.initials: JA
authors.lastname: Schulak
authors.forename: Paul F
authors.initials: PF
authors.lastname: Gores
authors.forename: Enrico
authors.initials: E
authors.lastname: Benedetti
authors.forename: Gabriel
authors.initials: G
authors.lastname: Danovitch
authors.forename: Alice K
authors.initials: AK
authors.lastname: Henning
authors.forename: Marilyn R
authors.initials: MR
authors.lastname: Bartucci
authors.forename: Sarah
authors.initials: S
authors.lastname: Smith
authors.forename: William E
authors.initials: WE
authors.lastname: Fitzsimmons
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D016035:Pancreas Transplantation / Q000276:immunology*; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2