Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study
Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study
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DOI：
10.1371/journal.pone.0104408
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发表时间：
2014-08-11
期刊：
影响因子：
3.7
通讯作者：
Riella, Leonardo V.
中科院分区：
文献类型：
--
作者：
Grafals, Monica;Smith, Brian;Riella, Leonardo V.
兔抗胸腺细胞球蛋白 (ATG) 通常用作肾移植受者的诱导治疗，但基于他克莫司的早期类固醇戒断方案中的理想剂量尚未确定。该试点研究的目的是确定低剂量 ATG 对低免疫风险肾移植受者的免疫表型和疗效。在这项前瞻性研究中，45 名患者被随机 (1:1) 接受我们的标准剂量 ATG（总剂量 3.75 mg/kg）(sATG) 与较低剂量 2.25 mg/kg (lowATG)。所有患者均在 7 天内接受早期类固醇戒断。主要终点是 12 个月时活检证实的急性排斥反应。在基线、移植后 3、6、12 个月时对新鲜分离的 PBMC 进行前瞻性免疫表型分析。 sATG 和 lowATG 的急性排斥反应率分别为 17% 和 10%。两组中效应记忆 T 细胞、Treg 细胞和近期胸腺移出 T 细胞在移植后具有相似的动力学。两组之间的移植物存活率、患者存活率或感染率没有显着差异，但与低 ATG 组相比，sATG 组的白细胞减少症（43% vs. 30%）、CMV（8% vs. 0）和 BK（4% vs. 0）感染没有显着增加。总之，在接受类固醇戒断的低免疫风险肾接受者中，低剂量 ATG 似乎可以有效预防急性排斥反应和消耗 T 细胞，并可能降低感染并发症。有必要进行更大规模的研究来证实这些发现。
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.