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

Abstract

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. 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. 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. 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. 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.