title: A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring.
abstract: BACKGROUND
  New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocols that emphasize reduction or avoidance of steroids and calcineurin inhibitors.
  
  
  METHODS
  In a randomized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors, group A received Thymoglobulin, group B received Alemtuzumab, and group C received Daclizumab. Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms, and methylprednisolone in groups A and C only (standard clinical institutional practice). The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C, respectively, with a targeted mycophenolate dose of 1 g twice daily. However, in group B, the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity, with 500 mg twice-daily doses of mycophenolate, without steroid maintenance.
  
  
  RESULTS
  In this 15-month median postoperative interval report, there were no notable differences in demographics and patient and graft survivals. Acute rejection rates at 1 year were equivalent, that is, 5 of 30 in all three groups (16.6%). In group B, there was slightly lower renal function at 1 month, but no difference at 1 year. There was also significantly more leukopenia, but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis, respectively, in group B.
  
  
  CONCLUSIONS
  This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.
authors.affiliation: Dept. of Surgery, The Lillian Jean Kaplan Renal Transplant Center of the Division of Transplantation, University of Miami Leonard M. Miller School of Medicine, and the Miami Veterans Affairs Medical Center, Miami, Florida 33101, USA. gciancio@med.miami.edu
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ciancio
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gaynor
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Carreno
authors.forename: Robert E
authors.initials: RE
authors.lastname: Cirocco
authors.forename: James M
authors.initials: JM
authors.lastname: Mathew
authors.forename: Adela
authors.initials: A
authors.lastname: Mattiazzi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cordovilla
authors.forename: David
authors.initials: D
authors.lastname: Roth
authors.forename: Warren
authors.initials: W
authors.lastname: Kupin
authors.forename: Anne
authors.initials: A
authors.lastname: Rosen
authors.forename: Violet
authors.initials: V
authors.lastname: Esquenazi
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakis
authors.forename: Joshua
authors.initials: J
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000097:blood / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D004268:DNA-Binding Proteins / Q000097:blood; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015415:Biomarkers; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D003404:Creatinine; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone