Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study

• Published in: PloS one Vol. 9; no. 8; p. e104408
• Main Authors: Grafals, Monica, Smith, Brian, Murakami, Naoka, Trabucco, Agnes, Hamill, Katherine, Marangos, Erick, Gilligan, Hannah, Pomfret, Elizabeth A, Pomposelli, James J, Simpson, Mary A, Azzi, Jamil, Najafian, Nader, Riella, Leonardo V
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.08.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antilymphocyte serum; Antilymphocyte Serum - adverse effects; Antilymphocyte Serum - economics; Antilymphocyte Serum - pharmacology; Biology and Life Sciences; Biopsy; Complications; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug dosages; Effectiveness; Effector cells; Female; Globulins; Graft rejection; Graft Rejection - immunology; Graft Rejection - prevention & control; Hospitals; Humans; Immunological memory; Immunology; Immunophenotyping; Immunosuppression; Induction therapy; Infections; Kidney transplantation; Kidney Transplantation - adverse effects; Kidneys; Kinetics; Leukopenia; Lymphocytes; Lymphocytes T; Male; Medical schools; Medicine and Health Sciences; Memory cells; Middle Aged; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - pharmacology; Patients; Physicians; Pilot Projects; Rabbits; Randomization; Rejection; Risk; Statistical analysis; Steroids - therapeutic use; Surgeons; Surgery; Survival; T-Lymphocytes - drug effects; Tacrolimus; Tacrolimus - pharmacology; Thymocytes; Thymus; Time Factors; Transplants & implants; Withholding Treatment; Womens health; New York; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104408

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. ClinicalTrials.gov NCT00548405.