Levels of serum VEGF-C/D and CXCL-12 are related to the severity of proteinuria in diabetic nephropathy

Abstract Objective To investigate the relationship between serum levels of lymphangiogenic factors and type 2 diabetic nephropathy and to evaluate the role of lymphangiogenesis in diabetic nephropathy. Methods The patients were divided into a normal albuminuria group (UmAlb  300 mg/24 h, n = 30), and 30 healthy individuals were enrolled as the healthy control group (n = 30). Levels of serum vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor-D (VEGF-D) and chemokine ligand 12 (CXCL-12) were quantified by enzyme-linked immunosorbent assay kits. Results The serum levels of VEGF-C,VEGF-D and CXCL-12 were significantly increased in all type 2 diabetic nephropathy groups. The correlation analysis showed that serum levels of VEGF-C, VEGF-D and CXCL-12 were positively correlated with serum creatinine and urinary microalbumin, and negatively correlated with estimated glomerular filtration rate. For discriminating the DN patients in the massive albuminuria group, microalbuminuria group and normal albuminuria group, the areas under the receiver operating characteristic curve (AUC-ROCs) for VEGF-C were 0.668 (95%CI: 0.531–0.805), 0.799 (95%CI: 0.678–0.920), and 0.850 (95%CI: 0.756–0.944); when the cutoff values were 152.40, 196.05 and 214.60 pg/ml, and the sensitivity was 93.3%, 96.7% and 100.0%, the specificity was 40.0%, 50.0% and 56.7%, respectively. Conclusion Serum VEGF-C,VEGF-D and CXCL-12 levels gradually increased in diabetic nephropathy, which has high value for the early diagnosis and evaluation of disease severity in diabetic nephropathy. These findings suggest that serum VEGF-C,VEGF-D and CXCL-12 levels may be a useful surrogate marker of clinical outcome in DN.