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早产儿急性肾损伤早期尿液生物标志物的蛋白质组学鉴定。

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

机构信息

Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea.

Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, South Korea.

出版信息

Sci Rep. 2020 Mar 4;10(1):4057. doi: 10.1038/s41598-020-60890-x.

Abstract

The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1 targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.

摘要

未成熟的早产儿肾脏容易受到急性肾损伤(AKI)的影响。然而,目前用于 AKI 的生物标志物既不敏感也不特异,也不能及时检测早产儿的 AKI。本研究的目的是使用蛋白质组学技术鉴定 AKI 的新型尿生物标志物,并验证和验证候选物是否可以作为 AKI 的早期预测生物标志物。在发现阶段共鉴定了 1810 种蛋白质。在这些蛋白质中,选择了 174 种作为 1 种靶蛋白。总共定量了 168 种蛋白质,在验证阶段,AKI 组中 6 种的水平显著升高。使用临床检测方法,使用生物库中出生后第一次尿液的样本对结果进行了确认和验证。最后,酶联免疫吸附试验显示,AKI 患者第一次尿液样本中的 annexin A5、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和蛋白 S100-P 水平明显高于无 AKI 患者。总之,尿 annexin A5、NGAL 和蛋白 S100-P 水平是预测早产儿 AKI 的早期、准确的有前途的生物标志物。

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