title: Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study.
abstract: Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00548405.
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America; Department of Medicine, Georgetown University, Washington, D.C., United States of America.
authors.forename: Monica
authors.initials: M
authors.lastname: Grafals
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Smith
authors.affiliation: Department of Medicine, Beth Israel Medical Center, New York, New York, United States of America.
authors.forename: Naoka
authors.initials: N
authors.lastname: Murakami
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: Agnes
authors.initials: A
authors.lastname: Trabucco
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Hamill
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: Erick
authors.initials: E
authors.lastname: Marangos
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: Hannah
authors.initials: H
authors.lastname: Gilligan
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Pomfret
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pomposelli
authors.affiliation: Department of Transplant Surgery, Lahey Clinic Medical Center, Burlington, Massachusetts, United States of America.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Simpson
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jamil
authors.initials: J
authors.lastname: Azzi
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Nephrology, Cleveland Clinic Florida, Weston, Florida, United States of America.
authors.forename: Nader
authors.initials: N
authors.lastname: Najafian
authors.affiliation: Transplantation Research Center, Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Leonardo V
authors.initials: LV
authors.lastname: Riella
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000191:economics / Q000494:pharmacology*; D003362:Cost-Benefit Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010865:Pilot Projects; D011817:Rabbits; D012306:Risk; D013256:Steroids / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D028761:Withholding Treatment
chemical_list: D000961:Antilymphocyte Serum; D013256:Steroids; D009173:Mycophenolic Acid; D016559:Tacrolimus
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