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Netrin-1与聚集素:重型β地中海贫血患儿早期肾损伤潜在的创新诊断生物标志物

Netrin-1 and clusterin: Innovative potential diagnostic biomarkers for early renal damage in β-thalassemia major children.

作者信息

Abd El-Khalik Sarah Ragab, Sharaby Radwa Mahmoud, Nasif Elham, Hamza Mohamed Bassiony, Ibrahim Rowida Raafat

机构信息

Medical Biochemistry & Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

IUBMB Life. 2021 May;73(5):800-810. doi: 10.1002/iub.2464. Epub 2021 Mar 23.

Abstract

BACKGROUND

Children with β-thalassemia major (β-TM) suffer from tubular dysfunction even before the onset of any renal impairment symptoms and/or clinical signs. Therefore, identifying innovative biomarkers allowing early renal damage detection has focused attention.

AIM

This study aims to preliminary assess Netrin-1(NTN-1) and clusterin (CLU) in β-TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction.

SUBJECTS AND METHODS

In this study, 40 β-TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN-1 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real-time PCR. Serum TNF-α, MDA levels and GST activity were measured.

RESULTS

Urinary NTN-1 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in β-TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in β-TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN-1 and CLU levels are of promising diagnostic performance.

CONCLUSION

Our results suggest that NTN-1 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in β-TM children. Moreover, urinary NTN-1 is recommended as a precise one during the clinical practices.

摘要

背景

重型β地中海贫血(β-TM)患儿甚至在出现任何肾功能损害症状和/或临床体征之前就存在肾小管功能障碍。因此,寻找能够早期检测肾脏损伤的新型生物标志物备受关注。

目的

本研究旨在初步评估β-TM患儿的Netrin-1(NTN-1)和簇集素(CLU),并探讨它们作为肾小管功能障碍替代无创生物标志物的可能作用。

对象与方法

本研究纳入了40例β-TM患儿和30例健康儿童。测定了常规血清和尿液生化指标。采用ELISA法检测尿NTN-1和CLU水平,采用实时PCR法检测其在PBMCs中的mRNA表达。检测血清TNF-α、MDA水平和GST活性。

结果

与对照组相比,β-TM患儿尿NTN-1和CLU浓度及PBMCs中mRNA相对表达水平显著升高。与对照组相比,β-TM患儿的氧化应激和炎症标志物显著升高。这些参数的变化与其他肾脏参数显著相关。ROC曲线分析表明,尿NTN-1和CLU水平具有良好的诊断性能。

结论

我们的结果表明,NTN-1和CLU有资格作为早期检测β-TM患儿肾损伤的新型无创生物标志物组合。此外,在临床实践中,推荐尿NTN-1作为一种精确的生物标志物。

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