Faculty Collaboration Database

Prospective randomized controlled trial of rabbit antithymocyte globulin compared with IL-2 receptor antagonist induction therapy in kidney transplantation. Ann Surg 2014 May;259(5):888-93

Date

02/12/2014

Pubmed ID

24513787

DOI

10.1097/SLA.0000000000000496

Scopus ID

2-s2.0-84899483553 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

OBJECTIVE: The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression.

BACKGROUND: The optimal induction therapy in patients at risk for rejection, particularly black recipients, in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear.

METHODS: This was a prospective, risk-stratified, randomized, single-center, open-label study of 200 consecutively enrolled patients in a large academic teaching center. Patients were randomized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were stratified between groups to ensure equal numbers of black, retransplants, high panel reactive antibodies (PRAs) (>20%), and prolonged cold ischemic times (>24 hours) in each group. Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance. Patients were followed up for 12 months. Renal transplant recipients were included if they were adult (≥18 years old) and received an allograft from a deceased, living unrelated, or nonhuman leukocyte antigen identical living-related donor.

RESULTS: A total of 200 patients (n = 98 in the interleukin-2 receptor antagonists, and n = 102 in the RATG) were enrolled from February 2009 through July 2011. One-year acute rejection rates were low and similar between groups (10% in the interleukin-2 receptor antagonist group vs 6% in the RATG group; P = 0.30). Creatinine clearance was also similar between groups (interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2; P = 0.73). Subanalysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection, without an increased risk of infection. Induction did not affect rejection rates according to recipient calculated PRAs; however, RATG was associated with an increased risk of BK virus in low-PRA patients.

CONCLUSIONS AND RELEVANCE: RATG induction provides improved protection against early acute rejection in black renal transplant recipients, whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy. This study is registered at Clinicaltrials.gov (NCT00859131).

Author List

Pilch NA, Taber DJ, Moussa O, Thomas B, Denmark S, Meadows HB, McGillicuddy JW, Srinivas TR, Baliga PK, Chavin KD

Author

Beje Thomas MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Animals
Antibodies, Blocking
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antilymphocyte Serum
Biopsy
Drug Therapy, Combination
Follow-Up Studies
Graft Rejection
Humans
Immunoglobulin G
Immunosuppressive Agents
Induction Chemotherapy
Kidney Transplantation
Middle Aged
Prospective Studies
Rabbits
Receptors, Interleukin-2
Recombinant Fusion Proteins
Treatment Outcome
Young Adult