{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:12:50Z","timestamp":1780089170154,"version":"3.54.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Children with \u03b2\u2010thalassemia major (\u03b2\u2010TM) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aims to preliminary assess Netrin\u20101(NTN\u20101) and clusterin (CLU) in \u03b2\u2010TM children and explore their possible roles as surrogate noninvasive biomarkers of renal tubular dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and methods<\/jats:title><jats:p>In this study, 40 \u03b2\u2010TM children and 30 healthy children were enrolled. Routine serum and urinary biochemical variables were determined. Urinary NTN\u20101 and CLU levels were measured using ELISA and their mRNA expression in PBMCs were assayed using real\u2010time PCR. Serum TNF\u2010\u03b1, MDA levels and GST activity were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urinary NTN\u20101 and CLU concentrations and mRNA relative expression levels in PBMCs were significantly increased in \u03b2\u2010TM children relative to controls. Oxidative stress and inflammatory markers revealed significant elevation in \u03b2\u2010TM children compared to controls. The change in these parameters correlated significantly with other renal parameters. ROC curves analysis showed that urinary NTN\u20101 and CLU levels are of promising diagnostic performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that NTN\u20101 and CLU are qualified as new noninvasive biomarker panels for early detection of renal injury in \u03b2\u2010TM children. Moreover, urinary NTN\u20101 is recommended as a precise one during the clinical practices.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iub.2464","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T12:39:23Z","timestamp":1615725563000},"page":"800-810","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Netrin\u20101 and clusterin: Innovative potential diagnostic biomarkers for early renal damage in \u03b2\u2010thalassemia major children"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-9899","authenticated-orcid":false,"given":"Sarah Ragab","family":"Abd El\u2010Khalik","sequence":"first","affiliation":[{"name":"Medical Biochemistry &amp; Molecular Biology Department Faculty of Medicine, Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwa 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