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基于血清靶向 HILIC-MS 代谢组学分析婴儿肾盂输尿管连接部梗阻

Serum-Targeted HILIC-MS Metabolomics-Based Analysis in Infants with Ureteropelvic Junction Obstruction.

机构信息

Paediatric Nephrology Unit, First Department of Paediatrics, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.

Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.

出版信息

J Proteome Res. 2020 Jun 5;19(6):2294-2303. doi: 10.1021/acs.jproteome.9b00855. Epub 2020 May 12.

DOI:10.1021/acs.jproteome.9b00855
PMID:32351114
Abstract

Ureteropelvic junction obstruction (UPJO) constitutes the predominant cause of obstructive nephropathy in both neonates and infants. Fundamental questions regarding UPJO's mechanism, assessment, and treatment still remain unanswered. The aim of the present study was to elucidate potential differences through serum metabolic profiling of surgical cases of infants with UPJO compared to both nonsurgical cases and healthy age-matched controls. Early diagnosis of renal dysfunction in this cohort based on highlighted biomarkers was the ultimate goal. Thus, serum samples were collected from 20 patients preoperatively, 19 patients with mild stenosis treated conservatively, and 17 healthy controls. All samples were subjected to targeted metabolomics analysis by hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS). Both univariate and multivariate statistical analyses were performed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) score plots showed that the studied groups differed significantly, with a panel of metabolites, including creatinine, tryptophan, choline, and aspartate, distinguishing patients who required surgery from those followed by systematical monitoring as well as from healthy controls, showing high performance as indicators of UPJO disease.

摘要

肾盂输尿管连接部梗阻 (UPJO) 是新生儿和婴儿梗阻性肾病的主要原因。关于 UPJO 的发病机制、评估和治疗,仍有一些基本问题尚未得到解答。本研究的目的是通过比较 UPJO 手术病例与非手术病例和健康年龄匹配对照者的血清代谢组学分析来阐明潜在差异。最终目标是根据突出的生物标志物对该队列中的肾功能障碍进行早期诊断。因此,从 20 例术前患者、19 例轻度狭窄接受保守治疗的患者和 17 例健康对照者中采集了血清样本。所有样本均通过亲水相互作用液相色谱与质谱联用 (HILIC LC-MS/MS) 进行靶向代谢组学分析。进行了单变量和多变量统计分析。主成分分析 (PCA) 和正交偏最小二乘判别分析 (OPLS-DA) 得分图表明,研究组之间存在显著差异,一组代谢物,包括肌酐、色氨酸、胆碱和天冬氨酸,可区分需要手术的患者与接受系统监测的患者以及健康对照者,显示出作为 UPJO 疾病指标的高性能。

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