Molecular Mechanisms of Diabetic Kidney Disease

Abstract

The inflammatory component of diabetic kidney disease has become of great interest in recent years, with genetic and epigenetic variants playing a fundamental role in the initiation and progression of the disease. Cells of the innate immune system play a major role in the pathogenesis of diabetic kidney disease, with a lesser contribution from the adaptive immune cells. Other components such as the complement system also play a role, as well as specific cytokines and chemokines. The inflammatory component of diabetic kidney disease is of great interest and is an active research field, with the hope to find potential innovative therapeutic targets.

Keywords: adaptive; cytokines; epigenetic; genetics; inflammatory; innate; innovation.

Figure 1

Diabetes mellitus leads to both hemodynamic factors, which include increased blood pressure and intraglomerular pressure, and metabolic factors (including protein kinase C, Hexosamine, polyol and AGE-related pathways leading to ROS and activation of signaling pathways leading to inflammation and DKD.

Figure 2

Hyperglycemia leads to the production of pro-inflammatory cytokines and chemokines in several cell types in the kidney including endothelial cells, mesangial cells, podocytes and tubular epithelial cells, causing inflammation via signaling pathways such as the JAK/STAT, TGF- β, Notch among others, leading to fibrosis.

Figure 3

Aldosterone elevated blood pressure leading to tissue injury via ROS, increasing the brain to spleen sympathetic drive, which leads to activation of innate immunity. Cytokines such as IL-6 and IL-1β lead to the activation the adaptive immune system, which leads to further tissue inflammation and fibrosis.