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用于评估新生儿科中毒性肾病和急性肾损伤(AKI)的新兴生物标志物和代谢组学

Emerging biomarkers and metabolomics for assessing toxic nephropathy and acute kidney injury (AKI) in neonatology.

作者信息

Mussap M, Noto A, Fanos V, Van Den Anker J N

机构信息

Department of Laboratory Medicine, IRCCS San Martino-IST, University Hospital, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genoa, Italy.

Department of Pediatrics and Clinical Medicine, Section of Neonatal Intensive Care Unit, Puericulture Institute and Neonatal Section, Azienda Mista and University of Cagliari, 09042 Cagliari, Italy.

出版信息

Biomed Res Int. 2014;2014:602526. doi: 10.1155/2014/602526. Epub 2014 Jun 11.

Abstract

Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called "omics" allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods.

摘要

鉴定新型药物性中毒性肾病和急性肾损伤(AKI)生物标志物已被美国肾脏病学会列为首要任务。生物学和医学领域知识的不断增加,促使人们发现了更多新的生物标志物及其在生理和病理条件触发的分子途径中的作用。与此同时,所谓的“组学”技术的发展,使得大量信息能够逐步应用于临床,这些信息涵盖了从人类基因组(基因组学)、蛋白质组(蛋白质组学),包括新兴的表观基因组学,到代谢物(代谢组学)等多个方面。在早产儿中,导致AKI发病和进展的最重要因素之一是个体遗传密码、环境、胎龄和疾病之间的相互作用。通过分析少量尿液样本,代谢组学能够即时识别表型的任何变化,包括基因修饰引起的变化。液相色谱 - 质谱联用(LC-MS)、质子核磁共振(1H NMR)及其他新兴技术发挥着关键作用,从根本上推动了新的生化和分子检测方法的迅速发展。尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)和肾损伤分子-1(KIM-1)与肾损伤的严重程度密切相关,是用于诊断、监测和量化肾损伤的非侵入性敏感替代生物标志物。要成为常规检测项目,uNGAL和KIM-1应在多中心临床试验中进行仔细测试,并应采用可靠、标准化的分析方法在生物体液中进行检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7889/4071811/4088e955df88/BMRI2014-602526.001.jpg

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