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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 cytometric analyses of Tregs and recent thymic emigrants (RTE) CD4 cells at different time points after transplantation.Representative contour plots of Tregs (A) (CD25+Foxp3+ of CD4+ cells) and RTEs (D) (CD45RA+CD31+ of CD4+ cells) cells after gating on CD4+ T cells at different time points after transplantation. Percentage of Tregs (B) and ratio of Tregs related to baseline (C) at different points after transplantation. E, Percentage of RTEs at different points after transplantation. Data are expressed as mean and standard deviation (n = 18-20 per group).
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pone-0104408-g004: Flow cytometric analyses of Tregs and recent thymic emigrants (RTE) CD4 cells at different time points after transplantation.Representative contour plots of Tregs (A) (CD25+Foxp3+ of CD4+ cells) and RTEs (D) (CD45RA+CD31+ of CD4+ cells) cells after gating on CD4+ T cells at different time points after transplantation. Percentage of Tregs (B) and ratio of Tregs related to baseline (C) at different points after transplantation. E, Percentage of RTEs at different points after transplantation. Data are expressed as mean and standard deviation (n = 18-20 per group).

Mentions: We compared the kinetics of peripheral blood T cell subsets at baseline and at 3, 6 and 12 months post-transplant between groups (Figure 3, 4). While CD8 T cells were recovered close to baseline after 3 months on both groups, CD4 T cells were persistently lower in both groups up to 12 months post-transplant (20±7.1% lowATG vs. 17±3.6% high ATG compared to baseline 35±3.6% and 37±5.5%, respectively) (Figure 3B). Overall, the percentage of effector memory T cells (CD45RO+CD62Llow) was reduced at 3 months after transplantation but increased after that, reaching its highest percentage at 12 months (Figure 3C). Tregs' percentage slightly increased post-transplant in both groups, though the standard deviations were wide and differences non-significant (Figure 4B).


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 cytometric analyses of Tregs and recent thymic emigrants (RTE) CD4 cells at different time points after transplantation.Representative contour plots of Tregs (A) (CD25+Foxp3+ of CD4+ cells) and RTEs (D) (CD45RA+CD31+ of CD4+ cells) cells after gating on CD4+ T cells at different time points after transplantation. Percentage of Tregs (B) and ratio of Tregs related to baseline (C) at different points after transplantation. E, Percentage of RTEs at different points after transplantation. Data are expressed as mean and standard deviation (n = 18-20 per group).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104408-g004: Flow cytometric analyses of Tregs and recent thymic emigrants (RTE) CD4 cells at different time points after transplantation.Representative contour plots of Tregs (A) (CD25+Foxp3+ of CD4+ cells) and RTEs (D) (CD45RA+CD31+ of CD4+ cells) cells after gating on CD4+ T cells at different time points after transplantation. Percentage of Tregs (B) and ratio of Tregs related to baseline (C) at different points after transplantation. E, Percentage of RTEs at different points after transplantation. Data are expressed as mean and standard deviation (n = 18-20 per group).
Mentions: We compared the kinetics of peripheral blood T cell subsets at baseline and at 3, 6 and 12 months post-transplant between groups (Figure 3, 4). While CD8 T cells were recovered close to baseline after 3 months on both groups, CD4 T cells were persistently lower in both groups up to 12 months post-transplant (20±7.1% lowATG vs. 17±3.6% high ATG compared to baseline 35±3.6% and 37±5.5%, respectively) (Figure 3B). Overall, the percentage of effector memory T cells (CD45RO+CD62Llow) was reduced at 3 months after transplantation but increased after that, reaching its highest percentage at 12 months (Figure 3C). Tregs' percentage slightly increased post-transplant in both groups, though the standard deviations were wide and differences non-significant (Figure 4B).

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