Use of polyclonal antibodies in brain-dead donors in kidney transplantation

D. Kuzmin, V. Manukovsky, S. Bagnenko, O. Reznik, A. Ananiev, O. Vorobyeva, S. Vorobyev, D. V. Gogolev, V. S. Daineko, A. A. Kutenkov, N. A. Chichagova, I. V. Uliankina
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Abstract

Objective. The objective of this study is to develop a therapeutic strategy for protecting grafts in order to improve the efficiency of kidney transplantation (KT) using polyclonal antibodies (pAbs) through elimination of activated forms of neutrophils, chemo- and cytokines from the donor’s bloodstream, and a decrease in the level of expression of adhesion molecules on the renal vascular endothelium at the pre-transplant stage.Materials and methods. In 2017, we developed and for the first time applied a therapeutic strategy for ischemia-reperfusion injury (IRI) in a brain-dead donor (BDD). Given the limited time interval after brain death has been diagnosed, Timoglobulin (Sanofi Genzyme, France) was administered to the donor at a dose of 8 mg/kg intravenously for 6 hours. Before drug administration and immediately before the start of cold perfusion, a complete blood count and renal transplant biopsy were performed. The study group included 10 BDDs (mean age 39.3 ± 4.4 years) who received anti-thymocyte globulin (ATG). The comparison group included 10 BDDs (mean age 38.5 ± 4.3 years) who did not undergo the new strategy. Donor kidneys were transplanted to 40 recipients (average age 47.5 ± 4.3 years), who were also divided into 2 groups, depending on the graft received (with and without ATG). At the organ donation center, a biobank of specimens from donors of various categories, including those using the IRI therapeutic strategy and recipients for retrospective assessment of the effectiveness of pAbs, was formed.Results. Clinical blood test results show that in the ATG group, there was stable leukopenia (neutropenia and lymphopenia) of 1.46 ± 0.18x109/l. Fifteen (75%) recipients of kidneys obtained from donors with ATG had immediate graft function; in the control group – 10 (50%) recipients.Conclusion. Data obtained testify to the prospects of implementing the proposed strategy in clinical practice, which will improve the quality of the resulting grafts and their suitability for subsequent transplantation, prolong graft functioning due to elimination of leukocytes as a factor of IRI, prevention of early allograft nephropathy, increase in the donor pool by using expanded criteria donors (ECDs).
多克隆抗体在脑死亡供者肾移植中的应用
目标。本研究的目的是开发一种保护移植物的治疗策略,以提高肾移植(KT)的效率,利用多克隆抗体(pAbs)通过消除供体血液中活化的中性粒细胞、化学物质和细胞因子,并在移植前阶段降低肾血管内皮粘附分子的表达水平。材料和方法。2017年,我们开发并首次应用了脑死亡供体(BDD)缺血再灌注损伤(IRI)的治疗策略。鉴于脑死亡诊断后的时间间隔有限,以8 mg/kg的剂量静脉注射替莫球蛋白(法国赛诺菲健赞公司),持续6小时。在给药前和冷灌注开始前,进行全血细胞计数和肾移植活检。研究组纳入10例bdd患者(平均年龄39.3±4.4岁),均接受抗胸腺细胞球蛋白(ATG)治疗。对照组包括10例未接受新策略的bdd患者(平均年龄38.5±4.3岁)。将供肾移植给40名受者(平均年龄47.5±4.3岁),根据接受的移植(有和没有ATG)分为两组。在器官捐献中心,建立了一个生物样本库,其中包括使用IRI治疗策略的捐赠者和用于回顾性评估pab有效性的受体。临床血检结果显示,ATG组稳定白细胞减少(中性粒细胞减少和淋巴细胞减少)为1.46±0.18 × 109/l。15例(75%)从ATG供者获得的肾脏接受者立即具有移植功能;对照组10例(50%)。获得的数据证明了在临床实践中实施所提出的策略的前景,这将提高所产生的移植物的质量及其对后续移植的适用性,由于消除作为IRI因素的白细胞而延长移植物功能,预防早期同种异体移植肾病,通过使用扩大标准供体(ECDs)增加供体池。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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