Identification of urinary soluble E‐cadherin as a novel biomarker for diabetic nephropathy

Abstract Background Currently, early diagnosis of diabetic nephropathy (DN) remains a major challenge. Thus, more investigations into new DN‐related biomarkers are needed. Methods We employed urinary proteomic approach of fluorescence‐based difference gel electrophoresis (DIGE) and mass spectrometry to identify novel biomarkers in urine samples, which were from type 2 diabetes patients with normoalbuminuria (DM group), microalbuminuria (DN1 group), macroalbuminuria (DN2 group) and control group ( n = 8 in each group). The identified biomarker was further studied by western blot in urine samples ( n = 6 in each group) and immunohistochemistry in renal biopsies. Besides, the urinary level of biomarker was detected and analyzed using enzyme‐linked immunosorbent assay(ELISA) method ( n = 40 in each group). Results A novel DN‐related biomarker, urinary E‐cadherin, was identified by proteomic methods, which up‐regulated 1.3‐fold, 5.2‐fold and 8.5‐fold in DM, DN1 and DN2 groups compared with control group. Meanwhile, high expression of urinary soluble 80 kDa fragment of E‐cadherin (sE‐cadherin) was verified in DN groups by western blot. The ELISA data also demonstrated that urinary sE‐cadherin‐to‐creatinine ratio was significantly increased in DN1 and DN2 groups versus DM group or control group (2751.5 ± 164 and 5839.6 ± 428 vs 721.9 ± 93 or 652.7 ± 87 µg/g; p < 0.001). The sensitivity and specificity of urinary sE‐cadherin for diagnosis of DN were calculated as 78.8% (95% CI, 74–83%) and 80% (95% CI, 65–91%). Besides, immunohistochemical stain showed that E‐cadherin expression was markedly decreased in renal tubular epithelial cells of patients with DN versus healthy controls. Conclusions Urinary sE‐cadherin has a potential clinical diagnostic value for DN and E‐cadherin may participate in the pathogenesis of DN. Copyright © 2009 John Wiley & Sons, Ltd.