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重新评估兔抗胸腺细胞球蛋白在肾移植中的诱导治疗(RETHINK):北美儿科肾脏试验与协作研究(NAPRTCS)登记处分析

Reassessing Rabbit Antithymocyte Globulin Induction in Kidney Transplantation (RETHINK): An Analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry.

作者信息

Ashoor Isa F, Martz Karen, Galbiati Shirley, Beyl Robbie A, Dharnidharka Vikas R

机构信息

Division of Nephrology, Department of Pediatrics, LSU Health New Orleans, New Orleans, LA.

The Emmes Company, LLC, Rockville, MD.

出版信息

Transplant Direct. 2020 Aug 21;6(9):e598. doi: 10.1097/TXD.0000000000001042. eCollection 2020 Sep.

Abstract

BACKGROUND

There is no consensus on rabbit antithymocyte globulin (rATG) dose used for induction immunosuppression in pediatric kidney transplants. We aimed to identify whether a lower rATG dose provides safe and effective immunosuppression compared with a higher dose.

METHODS

We retrospectively analyzed all first-time kidney transplant recipients (aged <21 y) in the North American Pediatric Renal Trials and Collaborative Studies registry since 1998 on mycophenolate mofetil- and tacrolimus-based immunosuppression with rATG induction. An a priori cutoff of 7.5 mg/kg cumulative rATG dose was used to identify low (<7.5 mg/kg) and high (≥7.5 mg/kg) exposure groups. Primary outcome was time to first-acute rejection episode. Secondary outcomes included graft function, patient survival, hospitalizations due to infections, and time to first-posttransplant lymphoproliferative disorder episode.

RESULTS

Four hundred fifty-five patients met inclusion criteria (59% male, 49% whites, 26% blacks, 38% living donor source). Median cumulative rATG dose was 6.8 mg/kg with a median of 5 doses and a median 1.5 mg/kg/dose introduced at a median of postoperative 0 days. Sixty-four percent received <7.5 mg/kg total rATG. There was no difference in age at transplant, gender, race, end-stage renal disease causes, or HLA mismatch among groups. Time to first-acute rejection was similar ( = 0.07). There was no significant difference in graft or patient survival or time to posttransplant lymphoproliferative disorder. Hospitalization for infection rates was similar.

CONCLUSIONS

These data demonstrate a wide variation in cumulative rATG induction dose. A smaller rATG dose <7.5 mg/kg may provide effective and safe immunosuppression compared with a higher dose.

摘要

背景

对于小儿肾移植诱导免疫抑制时使用的兔抗胸腺细胞球蛋白(rATG)剂量,目前尚无共识。我们旨在确定较低剂量的rATG与较高剂量相比是否能提供安全有效的免疫抑制。

方法

我们回顾性分析了自1998年以来北美儿科肾脏试验和协作研究登记处所有首次接受肾移植的患者(年龄<21岁),这些患者采用基于霉酚酸酯和他克莫司的免疫抑制方案并使用rATG进行诱导。预先设定的累积rATG剂量截止值为7.5mg/kg,用于确定低暴露组(<7.5mg/kg)和高暴露组(≥7.5mg/kg)。主要结局是首次急性排斥反应发作的时间。次要结局包括移植肾功能、患者生存率、因感染导致的住院情况以及首次移植后淋巴细胞增殖性疾病发作的时间。

结果

455例患者符合纳入标准(59%为男性,49%为白人,26%为黑人,38%为活体供肾来源)。rATG累积剂量中位数为6.8mg/kg,中位数为5剂,中位数剂量为1.5mg/kg/剂,于术后0天开始使用。64%的患者接受的rATG总量<7.5mg/kg。各组间移植时年龄、性别、种族、终末期肾病病因或HLA错配情况无差异。首次急性排斥反应的时间相似(P = 0.07)。移植肾功能、患者生存率或移植后淋巴细胞增殖性疾病发作时间无显著差异。感染导致的住院率相似(P = 0.07)。

结论

这些数据表明rATG诱导剂量的累积差异很大。与较高剂量相比,较小剂量(<7.5mg/kg)的rATG可能提供有效且安全的免疫抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8e0/7447457/39c9485613d3/txd-6-e598-g002.jpg

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