Advanced glycation end-products and the kidney

• Published in: European journal of clinical investigation 2010-08, Vol.40 (8), p.742-755
• Main Authors: Busch, Martin, Franke, Sybille, Rüster, Christiane, Wolf, Gunter
• Format: Article
• Language: English
• Subjects: Advanced glycation end-products; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; cardiovascular disease; Cardiovascular Diseases - metabolism; chronic kidney disease; diabetes mellitus; Diabetic Nephropathies - metabolism; diabetic nephropathy; General aspects; Glycation End Products, Advanced - antagonists & inhibitors; Glycation End Products, Advanced - metabolism; Glycation End Products, Advanced - physiology; Humans; Kidney - metabolism; Kidney - physiology; Kidneys; Medical sciences; Nephrology. Urinary tract diseases; podocytes; RAGE; Receptor for Advanced Glycation End Products; Receptors, Immunologic - metabolism; Urinary system involvement in other diseases. Miscellaneous
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2010.02317.x

Eur J Clin Invest 2010; 40 (8): 742–755 Background  Advanced glycation end‐products (AGEs) are increased in situations with hyperglycemia and oxidative stress such as diabetes mellitus. They are products of nonenzymatic glycation and oxidation of proteins and lipids. The kidney plays an important role in clearance and metabolism of AGEs. Methods  Medline© and other relevant databases were searched. In addition, key review articles were scanned for relevant original publication. Finally, original data from our research group were also included. Results  Kidney podocytes and endothelial cells express specific receptors for AGEs. Their activation leads to multiple pathophysiological effects including hypertrophy with cell cycle arrest and apoptosis, altered migration, and generation of proinflammatory cytokines. AGEs have been primarily implicated in the pathophysiology of diabetic nephropathy and diabetic microvascular complications. AGEs are also involved in other primary renal diseases as well as in the development and progression of atherosclerosis. However, serum or plasma concentrations of AGEs do not correlate well with cardiovascular events in patients with chronic kidney disease (CKD). This is likely due to the fact that serum concentrations failed to correlate with AGEs deposited in target tissues. Several inhibitors of the AGE‐RAGE axis are currently tested for various indications. Conclusion  AGEs and their receptors are involved in the pathogenesis of vascular and kidney disease. The role of circulating AGEs as biomarkers for cardiovascular risk estimation is questionable. Whether putative inhibitors of AGEs will get the maturity for its therapeutic use in the future remains open.