Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.

Diabetic kidney disease (DKD) is one of the leading causes of death among patients diagnosed with diabetes mellitus. Despite the growing knowledge about the pathogenesis of DKD, we still do not have effective direct pharmacotherapy. Accurate blood sugar control is essential in slowing down DKD. It seems that metformin has a positive impact on kidneys and this effect is not only mediated by its hypoglycemic action, but also by direct molecular regulation of pathways involved in DKD. The molecular mechanism of DKD is complex and we can distinguish polyol, hexosamine, PKC, and AGE pathways which play key roles in the development and progression of this disease. Each of these pathways is overactivated in a hyperglycemic environment and it seems that most of them may be regulated by metformin. In this article, we summarize the knowledge about DKD pathogenesis and the potential mechanism of the nephroprotective effect of metformin. Additionally, we describe the impact of metformin on glomerular endothelial cells and podocytes, which are harmed in DKD.

Extracellular Vesicles-A New Potential Player in the Immunology of Renal Cell Carcinoma.

The incidence of renal cell carcinoma (RCC) has doubled in the developed world within the last fifty years, and now it is responsible for 2-3% of diagnosed cancers. The delay in diagnosis and the not fully understood pathogenesis are the main challenges that have to be overcome. It seems that extracellular vesicles (EVs) are one of the key players in tumor development since they ensure a proper microenvironment for the tumor cells. The stimulation of angiogenesis and immunosuppression is mediated by molecules contained in EVs. It was shown that EVs derived from cancer cells can inhibit T cell proliferation, natural killer lymphocyte activation, and dendritic cell maturation by this mechanism. Moreover, EVs may be a biomarker for the response to anti-cancer treatment. In this review, we sum up the knowledge about the role of EVs in RCC pathogenesis and show their future perspectives in this field.