Circulating miR-210 Predicts Survival in Critically Ill Patients with Acute Kidney Injury

Circulating miR-210 Predicts Survival in Critically Ill Patients with Acute Kidney Injury
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DOI:
10.2215/cjn.00430111
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发表时间:
2011-07-01
影响因子:
9.8
通讯作者:
Thum, Thomas
Thum, Thomas
中科院分区:
医学1区
文献类型:
--
作者:
Lorenzen, Johan M.;Kielstein, Jan T.;Thum, Thomas

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背景与目的MicroRNAs(miRNAs)是一类调控基因表达的小分子核糖核苷酸。MicroRNA以非常稳定的形式存在于血液中。我们测试了急性肾损伤(阿基)危重患者血浆中的循环miRNA在肾脏替代治疗开始时是否被解除调节并可能预测survival.Design,setting,participants,& measurements我们使用从阿基患者和健康对照的血浆中分离的RNA分析miRNA。通过实时定量PCR在77例急性肾损伤患者、30例年龄匹配的健康对照和18例急性心肌梗死危重患者中验证结果。结果肾损伤阿基患者血浆中miR-16和rni 12 -320的循环水平下调,而与健康对照(均P < 0.0001)和疾病对照(miR-210和miR-16:P < 0.0001; miR-320:P = 0.03)相比,miR-210上调。考克斯回归分析(P < 0.05)和Kaplan-Meier曲线分析(P = 0.03)显示miR-210是28天生存率的独立和强有力的预测因子。MiR-210可预测该患者队列的死亡率,并可作为反映细胞水平病理生理学变化的新型生物标志物阿基。Clin J Am Soc Nephrol 6:1540-1546,2011. doi:10.2215/CJN.00430111
Background and objectives MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form. We tested whether circulating miRNAs in the plasma of critically ill patients with acute kidney injury (AKI) at the inception of renal replacement therapy are deregulated and may predict survival.Design, setting, participants, & measurements We profiled miRNAs using RNA isolated from the plasma of patients with AKI and healthy controls. The results were validated in 77 patients with acute kidney injury, 30 age-matched healthy controls, and 18 critically ill patients with acute myocardial infarction by quantitative real-time PCR.Results Circulating levels of miR-16 and rni12-320 were downregulated in the plasma of kidney injury AKI patients, whereas miR-210 was upregulated compared with healthy controls (all P < 0.0001) and disease controls (miR-210 and miR-16: P < 0.0001; miR-320: P = 0.03). Cox regression (P < 0.05) and Kaplan-Meier curve analysis (P = 0.03) revealed miR-210 as an independent and powerful predictor of 28-day survival.Conclusions Circulating miRNAs are altered in patients with kidney injury AKI. MiR-210 predicts mortality in this patient cohort and may serve as a novel biomarker AKI reflecting pathophysiological changes on a cellular level. Clin J Am Soc Nephrol 6: 1540-1546, 2011. doi: 10.2215/CJN.00430111