Increased urinary excretion of orosomucoid is a risk predictor of diabetic nephropathy

Aim: Identification of the risk predictor of diabetic nephropathy (DN) remains a major challenge currently. Thus, proteomic approaches to identify DN-related biomarker were performed. Methods: A comparative proteomic approach of 2-D gel electrophoresis (2-DE) and mass spectrometry to identify biomarkers in urine samples from 12 DN patients (six type 1 and six type 2 diabetic patients) and six healthy controls. Then, the urinary level of identified protein biomarker was detected by immunoturbidimetry assay in urine samples from 90 type 1 and type 2 diabetic patients with normo-, micro- and macroalbuminuria (n = 30 in each group), and 30 healthy controls. Results: A novel DN-related protein, orosomucoid (alpha 1-acid glycoprotein), was identified by proteomic method. Its abundance was highly upregulated (>eightfold) in DN patients. The data of immunoturbidimetry assay showed urinary orosomucoid excretion rate (UOER) was gradually increased in the normo-, micro- and macroalbuminuria group versus control (0.71 +/- 0.41, 1.93 +/- 0.68, 2.88 +/- 0.94 vs 0.39 +/- 0.28 mu g/min, P < 0.05). The result indicated that UOER increased in early stage of DN and gradually increased with the development of DN. Also, Pearson's correlation analysis indicated UOER was positively correlated with urinary albumin excretion rate, serum creatinine and C-reactive protein (r = 0.830, 0.787 and 0.360, respectively; P < 0.05). Multivariate logistic regression analysis also showed that increased UOER was an independent risk factor for DN (odds ratio = 3.10, P < 0.0001). Conclusion: Urinary orosomucoid is a DN-related biomarker, which is associated with the development and progression of DN. Furthermore, increased UOER is an independent risk factor of DN.