Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition

Figure 1

A schematic overview on structures and mechanisms in the pathogenesis of diabetic nephropathy. The pathogenesis of diabetic nephropathy involves several mechanisms over the course of the disease. Hyperglycemia is the leading cause of diabetic nephropathy; however, other metabolic factors such as hypercholesterolemia also play a role. Genetic factors are prominent since only ca. 30% of diabetic patients develop diabetic nephropathy. Importantly, hypertension and hemodynamic factors in the kidney, that is, hyperfiltration contribute significantly to the development of the disease. These external factors are translated by several intracellular pathways such as NADPH or PKC into cell activation. Different cell types respond in a specific fashion. Growth factors such as VEGF or TGF-b and chemokines such as MCP-1 are expressed and lead to inflammation and proteinuria followed by fibrosis. AngII, angiotensin II; ET-1, endothelin-1; NADPH, nicotinamide adenine dinucleotide phosphate hydrogen; PKC, protein kinase C; ROS, reactive oxygen species; TGF, transforming growth factor; VEGF, vascular endothelial growth factors; FGF, fibroblast growth factor.