尿液 microRNAs 作为人类中毒性急性肾损伤的非侵入性生物标志物。
Urinary microRNAs as non-invasive biomarkers for toxic acute kidney injury in humans.
机构信息
Clinical Pharmacology and Toxicology Research Group, Biomedical Informatics and Digital Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
出版信息
Sci Rep. 2021 Apr 28;11(1):9165. doi: 10.1038/s41598-021-87918-0.
MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine samples from patients with Russell's viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 samples in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell's viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had > 17 fold change (p < 0.0001) and receiver operator characteristics area-under-curve (ROC-AUC) > 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.
体液中的 microRNAs 是检测肾脏和其他器官损伤的潜在生物标志物。我们对被罗素蝰蛇咬伤或在百草枯、草甘膦或草酸[伴或不伴急性肾损伤 (AKI)]后急性自服中毒的患者以及健康对照者的尿液样本中的 microRNAs 进行了分析。采用 TaqMan OpenArray qPCR 对每组 3 名患者（每种毒剂各 12 个样本）进行了 754 个 microRNAs 的发现分析。在此基础上，从这些患者中选择并验证了更大队列的 microRNAs（罗素蝰蛇咬伤=53 例，百草枯=51 例，草甘膦=51 例，草酸=40 例）和 27 例健康对照者。在发现和验证队列中，不同肾毒性药物中毒/中毒的患者尿液中的 microRNAs 表达明显升高。7 个 microRNAs 可区分所有 4 种肾毒性药物的严重 AKI 患者和无 AKI 患者。4 个 microRNAs（miR-30a-3p、miR-30a-5p、miR-92a 和 miR-204）的 fold change（FC）>17（p<0.0001），受试者工作特征曲线（ROC）下面积（AUC）>0.72。这些差异表达 microRNA 的靶 mRNA 的通路分析显示，与不同肾毒性信号通路的调节有关。总之，人类尿液中的 microRNAs 可以在急性损伤后早期识别中毒性 AKI。这些尿液 microRNAs 有可能作为早期非侵入性诊断 AKI 的生物标志物用于临床。
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