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低剂量抗胸腺细胞球蛋白对小儿肾移植受者并无劣于标准高剂量:来自小儿肾脏病研究联盟的报告。

Low-Dose Antithymocyte Globulin Has No Disadvantages to Standard Higher Dose in Pediatric Kidney Transplant Recipients: Report From the Pediatric Nephrology Research Consortium.

作者信息

Ashoor Isa F, Beyl Robbie A, Gupta Charu, Jain Amrish, Kiessling Stefan G, Moudgil Asha, Patel Hiren P, Sherbotie Joseph, Weaver Donald J, Zahr Rima S, Dharnidharka Vikas R

机构信息

Division of Nephrology, Department of Pediatrics, LSU Health New Orleans, New Orleans, Louisiana, USA.

Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

出版信息

Kidney Int Rep. 2021 Jan 17;6(4):995-1002. doi: 10.1016/j.ekir.2021.01.007. eCollection 2021 Apr.

Abstract

INTRODUCTION

Rabbit antithymocyte globulin (rATG) dosing strategies for induction in pediatric kidney transplantation vary between centers. It is not known whether a lower rATG induction dose provides safe and effective immunosuppression compared with a "standard" higher dose.

METHODS

We performed a retrospective multicenter study of all isolated first-time kidney transplant recipients <21 years old who received rATG induction between 1 January 2010 and 31 December 2014 at 9 pediatric centers. An cutoff of a 4.5-mg/kg cumulative rATG dose was used to identify low (≤ 4.5 mg/kg) and standard (> 4.5 mg/kg) exposure groups. Outcomes examined included 12 months posttransplant graft function (estimated glomerular filtration rate [eGFR]); the occurrence of acute rejection, donor-specific antibody (DSA), neutropenia, and viral infection (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and BK virus); and 24-month outcomes of posttransplant lymphoproliferative disorder (PTLD) occurrence and patient and graft survival.

RESULTS

Two hundred thirty-five patients were included. Baseline features of the low and standard rATG dose groups were similar. By 12 months, the rATG dose group had no significant impact on the occurrence of neutropenia, positive DSA, or viral polymerase chain reaction (PCR). Graft function was similar. Acute rejection rates were similar at 17% (low dose) versus 19% (standard dose) ( = 0.13). By 24 months, graft survival (96.4% vs. 94.6%) and patient survival (100% vs. 99.3%) were similar between the low- and standard-dose groups ( = 0.54 and 0.46), whereas the occurrence of PTLD trended higher in the standard-dose group (0% vs. 2.6%,  = 0.07).

CONCLUSION

A low rATG induction dose ≤ 4.5 mg/kg provided safe and effective outcomes in this multicenter low immunologic risk pediatric cohort. Prospective studies are warranted to define the optimal rATG induction dose in pediatric kidney transplantation.

摘要

引言

小儿肾移植诱导期使用兔抗胸腺细胞球蛋白(rATG)的给药策略在各中心之间存在差异。与“标准”高剂量相比,较低的rATG诱导剂量是否能提供安全有效的免疫抑制尚不清楚。

方法

我们对2010年1月1日至2014年12月31日期间在9个儿科中心接受rATG诱导的所有年龄小于21岁的首次孤立肾移植受者进行了一项回顾性多中心研究。采用4.5mg/kg的rATG累积剂量作为临界值,以确定低暴露组(≤4.5mg/kg)和标准暴露组(>4.5mg/kg)。所检查的结果包括移植后12个月的移植肾功能(估计肾小球滤过率[eGFR]);急性排斥反应、供者特异性抗体(DSA)、中性粒细胞减少症和病毒感染(巨细胞病毒[CMV]、爱泼斯坦-巴尔病毒[EBV]和BK病毒)的发生情况;以及移植后淋巴细胞增殖性疾病(PTLD)的发生情况和患者及移植物存活的24个月结果。

结果

共纳入235例患者。低剂量和标准剂量rATG组的基线特征相似。到12个月时,rATG剂量组对中性粒细胞减少症、DSA阳性或病毒聚合酶链反应(PCR)的发生没有显著影响。移植肾功能相似。急性排斥反应发生率相似,低剂量组为17%,标准剂量组为19%(P=0.13)。到24个月时,低剂量组和标准剂量组的移植物存活率(96.4%对94.6%)和患者存活率(100%对99.3%)相似(P=0.54和0.46),而标准剂量组PTLD的发生率呈上升趋势(0%对2.6%,P=0.07)。

结论

在这个多中心低免疫风险的儿科队列中,≤4.5mg/kg的低rATG诱导剂量产生了安全有效的结果。有必要进行前瞻性研究以确定小儿肾移植中rATG的最佳诱导剂量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d7/8071617/ff96b8593cae/fx1.jpg

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