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肾移植后线粒体膜电位与移植物功能延迟。

Mitochondrial membrane potential and delayed graft function following kidney transplantation.

机构信息

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Department of Surgery, NYU Langone Medical Center, New York, New York.

出版信息

Am J Transplant. 2019 Feb;19(2):585-590. doi: 10.1111/ajt.15174. Epub 2018 Dec 4.

DOI:10.1111/ajt.15174
PMID:30408329
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6349555/
Abstract

Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = 1.38 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

摘要

延迟移植物功能(DGF)使 20%-40%的死亡供体肾脏移植复杂化,与住院时间延长和随后的移植物失功有关。对特定移植物 DGF 风险的准确预测可以影响器官分配、患者咨询和术后计划。线粒体功能障碍是缺血再灌注损伤中组织健康的报告替代指标,也可能是器官移植后组织健康的替代指标。为了了解线粒体膜电位(MMP)在临床决策中的潜在应用,我们分析了较低的 MMP(衡量线粒体功能障碍的指标)是否与 DGF 有关。在一项前瞻性、单中心概念验证研究中,我们测量了 28 例死亡供体肾脏的移植前 MMP,并分析了 MMP 与 DGF 之间的关系。我们使用混合登记增强回归来调整供体和受体特征,通过利用 Scientific Registry of Transplant Recipients 数据最小化过度拟合。MMP 水平范围为 964-28333 单位。低 MMP 肾脏(MMP<4000)更可能来自女性供体(75%比 10%,P=0.002)和心脏死亡后捐献者(75%比 12%,P=0.004)。MMP 水平每降低 10%,DGF 的可能性就会增加 38%(调整后的优势比=1.38,P=0.01)。总之,MMP 可能是肾脏移植中组织健康的有前途的移植前替代指标,并且在进一步验证后,通过其与 DGF 的独立关联,可以改善临床决策。

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Superior Intrinsic Mitochondrial Respiration in Women Than in Men.女性内在线粒体呼吸功能优于男性。
Front Physiol. 2018 Aug 17;9:1133. doi: 10.3389/fphys.2018.01133. eCollection 2018.
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Mitochondria and Sex-Specific Cardiac Function.线粒体与性别特异性心脏功能。
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Sex-associated differences in mitochondrial function in human peripheral blood mononuclear cells (PBMCs) and brain.人类外周血单核细胞(PBMCs)和大脑中线粒体功能的性别相关差异。
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肾移植中的移植肾功能延迟:危险因素、后果及预防策略
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The synthetic cannabinoid XLR-11 induces in vitro nephrotoxicity by impairment of endocannabinoid-mediated regulation of mitochondrial function homeostasis and triggering of apoptosis.合成大麻素XLR-11通过损害内源性大麻素介导的线粒体功能稳态调节和触发细胞凋亡来诱导体外肾毒性。
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