Hu Qiongyuan, Ren Jianan, Wu Jie, Li Guanwei, Wu Xiuwen, Liu Song, Wang Gefei, Gu Guosheng, Ren Huajian, Hong Zhiwu, Li Jieshou
*Department of Surgery, Jinling Hospital, Medical School of Southeast University, Nanjing, China †Medical School of Nanjing University, Nanjing, China ‡Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Shock. 2017 Jul;48(1):11-17. doi: 10.1097/SHK.0000000000000830.
Recent studies showed that mitochondrial injury and mitochondrial DNA (mtDNA) damage are associated with the initiation and progression of acute kidney injury (AKI). However, practical limitations of existing assays of mitochondrial function have limited our ability to study the link between mitochondrial dysfunction and renal injury. Therefore, we evaluated urinary mtDNA (UmtDNA) as a biomarker of AKI in critical illness patients.
DNA was isolated from urine samples in surgical intensive care unit (SICU) patients and quantified by quantitative polymerase chain reaction (PCR). Correlation analyses showed the relationships between the UmtDNA and several biomarkers of renal dysfunction. Moreover, we evaluated the predictive and diagnostic values of UmtDNA in newly developed AKI, renal replacement therapy (RRT), and hospital mortality using receiver operating characteristics curves.
MtDNA were expressed as PCR threshold cycle (Tc) number. Lower Tc indicated increased urinary mtDNA concentration. The baseline UmtDNA levels were elevated in SICU patients especially in AKI patients, compared with that in healthy controls. UmtDNA Tc number inversely correlated with serum creatine and urinary neutrophil gelatinase-associated lipocalin and directly with estimated glomerular filtration rate. Furthermore, baseline UmtDNA levels had high effectiveness in predicting development of AKI, initiation of RRT, and hospital mortality.
Elevated UmtDNA levels could identify newly developed AKI and predict RRT or hospital mortality in SICU patients. UmtDNA Tc number correlated with markers of renal injury and dysfunction, suggesting the involvement of mitochondrial injury in kidney damage among surgical critical illness patients.
近期研究表明，线粒体损伤和线粒体DNA（mtDNA）损伤与急性肾损伤（AKI）的发生和发展相关。然而，现有线粒体功能检测方法的实际局限性限制了我们研究线粒体功能障碍与肾损伤之间联系的能力。因此，我们评估了尿线粒体DNA（UmtDNA）作为危重病患者急性肾损伤生物标志物的价值。
从外科重症监护病房（SICU）患者的尿液样本中提取DNA，并通过定量聚合酶链反应（PCR）进行定量分析。相关性分析显示了UmtDNA与几种肾功能障碍生物标志物之间的关系。此外，我们使用受试者工作特征曲线评估了UmtDNA在新发急性肾损伤、肾脏替代治疗（RRT）和医院死亡率方面的预测和诊断价值。
mtDNA以PCR阈值循环（Tc）数表示。较低的Tc表明尿mtDNA浓度升高。与健康对照组相比，SICU患者尤其是急性肾损伤患者的基线UmtDNA水平升高。UmtDNA Tc数与血清肌酐和尿中性粒细胞明胶酶相关脂质运载蛋白呈负相关，与估计肾小球滤过率呈正相关。此外，基线UmtDNA水平在预测急性肾损伤的发生、RRT的启动和医院死亡率方面具有较高的有效性。
UmtDNA水平升高可识别新发急性肾损伤，并预测SICU患者的RRT或医院死亡率。UmtDNA Tc数与肾损伤和功能障碍标志物相关，提示线粒体损伤参与了外科危重病患者的肾损伤。
