IGFBP5 activates the expression of 6-phosphofructose-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) via EGR1, enhances ECM production, thereby promoting the production of pro-inflammatory molecules including interleukin-6 (IL-6), TNF-α (tumor necrosis factor-α), the chemokine monocyte chemoattractant protein-1 (MCP-1), and the adhesion molecule intercellular adhesion molecule-1 (ICAM-1), increases macrophage migration, promotes glycolysis and inflammatory responses in ECs, enhances renal inflammation, and promotes DKD progression. Here, IL6 is linked to diabetic kidney disease.