Oxalic acid-induced nephrotoxicity and acute kidney injury result from formation of calcium oxalate crystals. Oxalic acid-induced acute kidney injury is a significant problem in many parts of the world. Circulating biomarkers that can accurately and reproducibly detect acute kidney injury are highly desirable. We used a high sensitivity discovery platform to identify signature microRNAs to distinguish healthy individuals never exposed to oxalic acid (n = 4) from those who were exposed to oxalic acid but had no injury (NOAKI; n = 4), moderate injury (AKIN2; n = 4) or severe injury (AKIN3; n = 4). Longitudinal analyses identified 4-8 h post-ingestion as the best time to detect AKIN2/3. We validated a signature of 53 microRNAs identified in the discovery, in a second cohort of individuals exposed to oxalic acid (NOAKI = 11, AKIN2 = 8 and AKIN3 = 18) and healthy controls (n = 19). Thirteen microRNAs were significantly downregulated in acute kidney injury patients compared to NOAKI within 8-h post-ingestion. Five microRNAs (miR-20a, miR-92a, miR-93, miR-195, miR-451) had a highly significant correlation with normalized urinary albumin, serum creatinine at 24 h and creatinine clearance. Logistic regression of these microRNAs had AUC-ROC of 0.85 predicting AKIN2/3 and discriminated patients from healthy controls (AUC-ROC = 0.93). mRNA targets of these microRNAs identified oxidative stress pathways of nephrotoxicity in proximal tubule and glomeruli nephrotoxicity. In conclusion, the downregulation of multiple circulating microRNAs in patients correlated with the severity of oxalic acid-induced acute kidney injury. A set of microRNAs (miR-20a, miR-92a, miR-93, miR-195, miR-451) could be promising biomarkers for early detection of oxalic acid-induced acute kidney injury.

中文翻译：

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草酸诱导的急性肾脏损伤的循环人类microRNA生物标志物。

草酸引起的肾毒性和急性肾损伤是由草酸钙晶体的形成引起的。草酸引起的急性肾损伤在世界许多地方都是一个重大问题。能够准确且可重复地检测急性肾损伤的循环生物标志物是非常需要的。我们使用了一个高灵敏度的发现平台来鉴定标志性microRNA，以区分从未接触过草酸（n = 4）的健康个体与未接触过草酸但无损伤（NOAKI; n = 4），中度损伤（AKIN2; n = 4）或严重伤害（AKIN3； n = 4）。纵向分析确定了摄取后4-8小时是检测AKIN2 / 3的最佳时间。在第二批暴露于草酸的个体中，我们验证了发现中鉴定的53个microRNA的签名（NOAKI = 11，AKIN2 = 8，AKIN3 = 18）和健康对照组（n = 19）。与NOAKI相比，急性肾损伤患者在摄入后8小时内有13种microRNA显着下调。五个microRNA（miR-20a，miR-92a，miR-93，miR-195，miR-451）与归一化尿白蛋白，24小时血清肌酐和肌酐清除率高度相关。这些微RNA的逻辑回归分析的AUC-ROC为0.85，预测为AKIN2 / 3，并将患者与健康对照区分开（AUC-ROC = 0.93）。这些microRNA的mRNA目标确定近端肾小管肾毒性和肾小球肾毒性的氧化应激途径。总之，患者体内多种循环microRNA的下调与草酸诱导的急性肾损伤的严重程度有关。一组microRNA（miR-20a，miR-92a，miR-93，miR-195，