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

Grafals M, Smith B, Murakami N, Trabucco A, Hamill K, Marangos E, Gilligan H, Pomfret EA, Pomposelli JJ, Simpson MA, Azzi J, Najafian N, Riella LV - PLoS ONE (2014)

Bottom Line: 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.A larger study is warranted to confirm these findings.

View Article: PubMed Central - PubMed

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.

ABSTRACT

Unlabelled: 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.

Trial registration: ClinicalTrials.gov NCT00548405.

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Related in: MedlinePlus

Flow diagram of patients screened and enrolled in the study.
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pone-0104408-g001: Flow diagram of patients screened and enrolled in the study.

Mentions: After the screening process, eligible patients were randomized in a 1∶1 ratio either to receive standard dose ATG of 1.25 mg/kg×3 doses (3.75 mg/kg total dose) [sATG] or low dose ATG of 0.75 mg/kg×3 doses (2.25 mg/kg total dose) [lowATG] (Figure 1). For obese patients, the maximum weight used in the dose calculation was 100 kg. After patient enrollment by a transplant nephrologist, computer-generated protocols were utilized for randomization (performed by research coordinator and implemented by transplant nephrologist).


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

Grafals M, Smith B, Murakami N, Trabucco A, Hamill K, Marangos E, Gilligan H, Pomfret EA, Pomposelli JJ, Simpson MA, Azzi J, Najafian N, Riella LV - PLoS ONE (2014)

Flow diagram of patients screened and enrolled in the study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128673&req=5

pone-0104408-g001: Flow diagram of patients screened and enrolled in the study.
Mentions: After the screening process, eligible patients were randomized in a 1∶1 ratio either to receive standard dose ATG of 1.25 mg/kg×3 doses (3.75 mg/kg total dose) [sATG] or low dose ATG of 0.75 mg/kg×3 doses (2.25 mg/kg total dose) [lowATG] (Figure 1). For obese patients, the maximum weight used in the dose calculation was 100 kg. After patient enrollment by a transplant nephrologist, computer-generated protocols were utilized for randomization (performed by research coordinator and implemented by transplant nephrologist).

Bottom Line: 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.A larger study is warranted to confirm these findings.

View Article: PubMed Central - PubMed

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.

ABSTRACT

Unlabelled: 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.

Trial registration: ClinicalTrials.gov NCT00548405.

Show MeSH
Related in: MedlinePlus