Advances in Targeting the AGEs-RAGE Pathway for the Treatment of Diabetic Kidney Disease

Diabetic kidney disease (DKD) represents the most severe microvascular complication of diabetes and is the leading cause of end-stage renal disease globally. Its pathogenesis is complex, and current treatments have limitations. Advanced glycation end products (AGEs) and AGEs receptor (RAGE), constitute a core mechanism driving DKD progression. AGEs accumulate abnormally in high-glucose environments. Upon activation, RAGE mediates oxidative stress, chronic inflammation, renal fibrosis, dysregulation of autophagy, and apoptosis through multiple signaling pathways, ultimately leading to damage to the glomerular filtration barrier and exacerbating renal injury from multiple dimensions. This paper aims to elucidate the role of the AGEs-RAGE pathway in DKD and systematically review therapeutic strategies targeting this pathway. These include AGEs antagonists, AGEs-RAGE axis modulators, RAGE ligand binding inhibitors, antibody-based therapeutics, and traditional Chinese medicine. Additionally, clinical studies of AGEs-RAGE axis-targeted drug therapies for DKD are analyzed. This paper provides theoretical foundations for developing novel therapeutic drugs in DKD.