Fig. 2: Overview of the pathogenesis of diabetic kidney disease (DKD).
From: Mitochondrial metabolic reprogramming in diabetic kidney disease
In a healthy kidney, the glomerular filtration barrier is formed by intact glomerular endothelial cells, basement membranes, and podocytes. This barrier effectively prevents the filtration of macromolecules like plasma albumin from the blood. The contractile action of mesangial cells regulate the tubular diameter of the afferent and efferent arterioles, thereby controlling the glomerular filtration rate. Additionally, mesangial cells support the position of vascular collaterals. Tubular epithelial cells play a role in regulating the formation of primary urine through functions like reabsorption, secretion, and excretion. However, hyperglycemia-induced changes in kidney hemodynamics, activation of the RASS, generation of AGEs leading to mitochondrial metabolic reprogramming, and excessive release of ROS trigger a cascade of signaling pathways, cytokines, and transcription factors. These factors contribute to the development of various pathological responses in renal cells, including inflammation, autophagy, apoptosis, and fibrosis.
