死亡捐赠器官的钙调素酶抑制剂作用：对临床前研究进行的系统综述和荟萃分析。
Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.
发表日期：2023 Sep
作者：
Frédérick D'Aragon, William Rousseau, Ruth Breau, Daniel Aminaei, Carole Ichai, Gordon J Boyd, Karen E A Burns, Héloïse Cardinal, François-Martin Carrier, Michaël Chassé, Prosanto Chaudhury, Sonny Dhanani, Shane W English, Anne Julie Frenette, Steven Hanna, Gregory Knoll, François Lauzier, Simon Oczkowski, Bram Rochwerg, Khaled Shamseddin, Marat Slessarev, Darin Treleaven, Alexis F Turgeon, Matthew J Weiss, Markus Selzner, Maureen O Meade
来源：
Burns & Trauma
摘要：
通过使用钙调神经酶抑制剂（calcineurin inhibitors, CNIs）对已故器官捐赠者进行预处理，可以减少缺血再灌注损伤，从而改善移植结果。我们检索了MEDLINE、EMBASE、Cochrane图书馆和会议文献，寻找进行器官捐赠和移植的动物模型，比较了接受CNIs治疗的捐赠者与接受安慰剂或无干预的捐赠者，并评估了器官移植的结果。评审员独立筛选和选择研究，提取数据，评估所包含研究的偏倚风险和临床相关性。在可能的情况下，我们使用荟萃分析汇总结果；否则，我们以描述性方式总结发现。18项研究使用不同动物和一系列CNI药物和剂量评估其对多种移植结果的影响。偏倚风险和临床适用性报道不足。荟萃分析提示CNI治疗对肾脏移植的早期移植物功能有益（3项研究；血清肌酐：均值比 [RoM] 0.54；95%可信区间 [CI]，0.34-0.86），但对肝脏移植无益（2项研究；血清丙氨酸氨基转移酶：RoM 0.61；95% CI，0.30- 1.26；以及血清天冬氨酸氨基转移酶：RoM 0.58；95% CI，0.26-1.31）。我们发现，在7天内没有减少移植物丧失（2项研究；风险比0.54；95% CI，0.08-3.42）。CNI治疗与减少移植受体白介素-6水平（4项研究；RoM 0.36；95% CI，0.19-0.70）、肿瘤坏死因子-α水平（5项研究；RoM 0.36；95% CI，0.12-1.03）和细胞凋亡（4项研究；RoM 0.30；95% CI，0.19-0.47）相关。尽管这些动物实验的文集暗示使用CNIs对捐赠者进行预处理可能改善肾脏移植的早期移植物功能，但在动物实验中无法真实重现临床环境，并且无法评估这些实验的偏倚风险，这是一个严重的弱点，导致当前无法进行临床应用。
Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes.We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively.Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47).Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.Copyright © 2023 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.