Proximal Tubule Dysfunction Is Associated with Podocyte Damage Biomarkers Nephrin and Vascular Endothelial Growth Factor in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

Background: There is an ongoing debate as to whether early diabetic nephropathy in Type 2 diabetes mellitus may be attributed to the glomerulus or to the proximal tubule. Urinary excretion of nephrin and vascular endothelial growth factor may increase even in the normoalbuminuria stage. In the course of diabetic nephropathy, the proximal tubule may be involved in the uptake of urinary nephrin and vascular endothelial growth factor. Materials and Methods: Two groups of consecutive Type 2 diabetes mellitus outpatients (38 normo-, 32 microalbuminuric) and 21 healthy subjects were enrolled in a cross-sectional study and evaluated concerning the relation of proximal tubule dysfunction with the podocyte biomarkers excretion, assessed by ELISA methods. The impact of advanced glycation end-products on this relation was also queried. Results: Urinary alpha1-microglobulin and kidney injury molecule-1 correlated with urinary albumin:creatinine ratio (R2 = 0.269; p,0.001; R2 = 0.125; p,0.001), nephrinuria (R2 = 0.529; p,0.001; R2 = 0.203; p,0.001), urinary vascular endothelial growth factor (R2 = 0.709; p,0.001; R2 = 0.360; p,0.001), urinary advanced glycation end-products (R2 = 0.578; p,0.001; R2 = 0.405; p,0.001), serum cystatin C (R2 = 0.130; p,0.001; R2 = 0.128; p,0.001), and glomerular filtration rate (R2 = 0.167; p,0.001; R2 = 0.166; p,0.001); nephrinuria and urinary vascular endothelial growth facto