Diabetic Kidney Disease, Endothelial Damage, and Podocyte-Endothelial Crosstalk

Abstract Diabetes-related complications are a significant source of morbidity and mortality worldwide. Diabetic kidney disease is a frequent microvascular complication and is a primary cause of kidney failure in patients with diabetes. The glomerular filtration barrier is composed of three layers, the endothelium, the glomerular basement membrane and the podocytes. The podocytes and the endothelium communicate through molecular crosstalk to maintain filtration at the glomerular filtration barrier. Chronic hyperglycemia affects all three layers of the glomerular filtration barrier as well as the molecular crosstalk that occurs between the two cellular layers. One of the earliest events following chronic hyperglycemia is endothelial cell dysfunction. Early endothelial damage is associated with the progression of diabetic kidney disease. However, current therapies are based in controlling glycemia and arterial blood pressure without targeting endothelial dysfunction. Disruption of the endothelial cell layer also alters the molecular crosstalk that occurs between the endothelium and the podocytes. This review discusses both the physiological and pathological communication that occurs at the glomerular filtration barrier. It examines how these signaling components contribute to podocyte foot effacement, podocyte detachment and the progression of diabetic kidney disease.