A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring.
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.
Ciancio
Gaetano
G
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
Burke
George W
GW
Gaynor
Jeffrey J
JJ
Carreno
Manuel R
MR
Cirocco
Robert E
RE
Mathew
James M
JM
Mattiazzi
Adela
A
Cordovilla
Tatiana
T
Roth
David
D
Kupin
Warren
W
Rosen
Anne
A
Esquenazi
Violet
V
Tzakis
Andreas G
AG
Miller
Joshua
J
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
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