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供体血浆线粒体 DNA 与移植后肾移植功能相关。

Donor Plasma Mitochondrial DNA Is Correlated with Posttransplant Renal Allograft Function.

机构信息

Division of Kidney Transplantation, Department of Surgery, Organ Transplantation Research Institution, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Center for Molecular Pathology, The First Affiliated Hospital, Gannan Medical University, Ganzhou, China.

出版信息

Transplantation. 2019 Nov;103(11):2347-2358. doi: 10.1097/TP.0000000000002598.

Abstract

BACKGROUND

The lack of accurate biomarkers makes it difficult to determine whether organs are suitable for transplantation. Mitochondrial DNA (mtDNA) correlates with tissue damage and kidney disease, making it a potential biomarker in organ evaluation.

METHODS

Donors who had experienced cardiac death and successfully donated their kidneys between January 2015 and May 2017 were included this study. We detected the level of mtDNA in the plasma of the donor using quantitative real-time polymerase chain reaction and then statistically analyzed the relationship between the level of mtDNA and the delayed graft function (DGF) of the recipient.

RESULTS

The incidence of DGF or slowed graft function (SGF) increased by 4 times (68% versus 16%, P < 0.001) when the donor mtDNA (dmtDNA) level was >0.114. When dmtDNA levels were >0.243, DGF and primary nonfunction were approximately 100% and 44%, respectively. Moreover, dmtDNA was an independent risk factor for slowed graft function and DGF. A prediction model for DGF based on dmtDNA achieved an area under the receiver operating characteristic curve for a prediction score as high as 0.930 (95% confidence interval 0.856-1.000), and the validation cohort results showed that the sensitivity and specificity of the model were 100% and 78%, respectively. dmtDNA levels were correlated with 6-month allograft function (R=0.332, P < 0.001) and 1-year graft survival (79% versus 99%, P < 0.001).

CONCLUSIONS

We conclusively demonstrated that plasma dmtDNA was an independent risk factor for DGF, which is valuable in organ evaluation. dmtDNA is a possible first predictive marker for primary nonfunction and worth further evaluation.

摘要

背景

缺乏准确的生物标志物使得确定器官是否适合移植变得困难。线粒体 DNA(mtDNA)与组织损伤和肾脏疾病相关,使其成为器官评估中的潜在生物标志物。

方法

本研究纳入了 2015 年 1 月至 2017 年 5 月期间经历心源性死亡并成功捐献肾脏的供体。我们使用实时定量聚合酶链反应检测供体血浆中的 mtDNA 水平,然后统计分析 mtDNA 水平与受体延迟移植物功能(DGF)之间的关系。

结果

当供体 mtDNA(dmtDNA)水平>0.114 时,DGF 或移植物功能缓慢(SGF)的发生率增加了 4 倍(68%比 16%,P<0.001)。当 dmtDNA 水平>0.243 时,DGF 和原发性无功能分别约为 100%和 44%。此外,dmtDNA 是 SGF 和 DGF 的独立危险因素。基于 dmtDNA 的 DGF 预测模型的预测评分曲线下面积高达 0.930(95%置信区间 0.856-1.000),验证队列结果表明模型的灵敏度和特异性分别为 100%和 78%。dmtDNA 水平与 6 个月移植物功能(R=0.332,P<0.001)和 1 年移植物存活率(79%比 99%,P<0.001)相关。

结论

我们明确表明,血浆 dmtDNA 是 DGF 的独立危险因素,在器官评估中具有价值。dmtDNA 可能是原发性无功能的第一个预测标志物,值得进一步评估。

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