Microvascular Damage and Hemodynamic Alterations in Diabetic Nephropathy

Abstract

Microvascular damage has a central role in the origination and progression of diabetic nephropathy. Manifestations of microvascular damage include rarefaction (reduced capillary density) and endothelial dysfunction. These alterations lead to hemodynamic abnormalities, contributing to the progression of diabetic nephropathy. Furthermore, besides microvascular damage in the kidney itself, diabetic nephropathy is also associated with microvascular changes in several other tissues. This suggests a common systemic microvascular damaging mechanism, which may include a variety of hypertension- and hyperglycemia-associated molecular pathways. The nature and extent of these pathways have yet to be fully uncovered and are subject to changing views. This also touches upon finding the optimal treatment to halt or reverse microvascular damage in diabetic nephropathy. New classes of antidiabetic drugs like SGLT2-inhibitors, DDP-4 inhibitors, and GLP-1 receptor agonist have shown promising results with regard to clinical outcomes but need to be further studied with regard to their effects on the renal microcirculation. Also, due to the involvement of a wide variability of mechanisms, finding one therapeutic agent optimally targeting the microcirculation will probably remain complicated.