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JRHMS 2025, 4(1): 46-53 |
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Kazemi H. The role of advanced glycation end products and RAGE in diabetic nephropathy: Pathophysiological mechanisms and therapeutic implications. JRHMS 2025; 4 (1) :46-53
URL: http://jrhms.thums.ac.ir/article-1-140-en.html
URL: http://jrhms.thums.ac.ir/article-1-140-en.html
Abstract: (2 Views)
Diabetic nephropathy (DN) is one of the most severe microvascular complications of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal failure worldwide. Persistent hyperglycemia triggers a network of pathogenic mechanisms, including increased formation of advanced glycation end products (AGEs), activation of the receptor for AGEs (RAGE), oxidative stress, chronic inflammation, and profibrotic signaling. AGEs accumulate in long-lived proteins and renal tissues under sustained hyperglycemia, and their interaction with RAGE activates multiple intracellular pathways that amplify oxidative damage, inflammatory mediator release, extracellular matrix deposition, and podocyte injury. The AGE/RAGE axis plays a central role in the development of glomerular hyperfiltration, albuminuria, mesangial expansion, basement membrane thickening, and progressive glomerulosclerosis. Furthermore, the phenomenon of metabolic memory indicates that early hyperglycemic exposure can induce long-term renal damage even after glycemic improvement. This review summarizes current insights into the molecular mechanisms linking AGE and RAGE to DN and highlights potential therapeutic strategies targeting this pathogenic pathway.
Keywords: Diabetic nephropathy, Advanced glycation end products, RAGE, Hyperglycemia, Oxidative stress, Renal fibrosis, Metabolic memory
Type of Study: Narrative Review |
Subject:
General
Received: 2026/05/4 | Accepted: 2026/05/4 | Published: 2026/05/23
Received: 2026/05/4 | Accepted: 2026/05/4 | Published: 2026/05/23
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