Circulating MicroRNA-188, -30a, and -30e as Early Biomarkers for Contrast-Induced Acute Kidney Injury.
Circulating MicroRNA-188, -30a, and -30e as Early Biomarkers for Contrast-Induced Acute Kidney Injury.
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循环 MicroRNA-188、-30a 和-30e 作为对比剂引起的急性肾损伤的早期生物标志物
DOI：
10.1161/jaha.116.004138
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发表时间：
2016-08-15
影响因子：
5.4
通讯作者：
He B
中科院分区：
文献类型：
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作者：
Sun SQ;Zhang T;Ding D;Zhang WF;Wang XL;Sun Z;Hu LH;Qin SY;Shen LH;He B
造影剂诱导的急性肾损伤（阿基）通常定义为血管内给予造影剂后血清肌酐升高。由于肌酐是肾功能急性变化的不可靠指标，我们评估了循环microRNA（miRNAs）是否可以作为早期检测阿基的生物标志物。使用阿基大鼠模型，我们首先评估了大鼠血浆和肾脏的miRNA谱。选择阿基大鼠血浆样品中增加>1.5倍的三种miRNA种类，包括miRNA-188、miRNA-30 a和miRNA-30 e作为候选miRNA。定量真实的时间聚合酶链反应显示，这些候选miRNA在造影剂暴露后约4小时浓度达到峰值，并且具有相对的肾脏特异性。我们比较了71名接受冠状动脉造影或经皮冠状动脉介入治疗并发生阿基的患者与71名匹配对照的这些候选miRNAs的血浆水平。与对照组相比，阿基组中3种候选miRNA的血浆水平显著升高。受试者操作特征分析显示，这些miRNA显著区分了阿基患者和非阿基患者。miRNA复合物对于阿基预测是高度准确的，如通过三重阳性miRNA复合物的最大化特异性或通过任何阳性miRNA复合物的最大化约登指数所示。此外，所选的miRNAs变化与代谢风险评分相关。候选miRNAs的血浆水平显著区分了阿基患者和非阿基患者。因此，miRNA是早期检测阿基的潜在生物标志物。
Contrast‐induced acute kidney injury (CI‐AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI‐AKI. Using a rat model of CI‐AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with >1.5‐fold increase in plasma samples of CI‐AKI rats, including miRNA‐188, miRNA‐30a, and miRNA‐30e, were selected as candidate miRNAs. Quantitative real‐time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4 hours after contrast medium exposure and were relatively renal‐specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI‐AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI‐AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI‐AKI from those without CI‐AKI. MiRNA composites were highly accurate for CI‐AKI prediction, as shown in maximized specificity by treble‐positive miRNA composite or maximized Youden index by any‐positive miRNA composite. Moreover, the selected miRNAs changes were associated with Mehran Risk Scores. Plasma levels of candidate miRNAs significantly distinguished patients with CI‐AKI from those without CI‐AKI. Thus, miRNAs are potential biomarkers for early detection of CI‐AKI.