title: AGEs/RAGE in CKD: irreversible metabolic memory road toward CVD?
abstract: BACKGROUND
  Cardiovascular disease is the major cause of death in patients with renal insufficiency, accounting for 50% of all deaths in renal replacement therapy patients. Mortality from cardiovascular diseases in these patients is approximately 9% per year, which is about 30 times the risk in the general population. So far, intensive interventions to the general risk factors, such as high LDL-cholesterol or C-reactive protein, have not been successful in improving their cardiovascular outcomes, suggesting that the beneficial effect of risk reduction may be overwhelmed by accumulated risk memorized by long-term exposure to oxidative stress during the progression of renal failure.
  
  
  METHODS
  In this review, we propose that this irreversible memory effect in renal failure may be mediated by advanced glycation end-products (AGEs).
  
  
  RESULTS
  The generation of AGEs has been implicated to be deeply associated with increased oxidative stress. Moreover, interaction of the receptor for AGEs (RAGE) with AGEs leads to crucial biomedical pathway generating intracellular oxidative stress and inflammatory mediators, which could result in further amplification of the pathway involved in AGE generation. Several lines of evidence suggest that AGEs/RAGE axis can profoundly be involved in cardiovascular diseases. Recent advances in AGEs and RAGE measurements led us to be capable of understanding more about the role of AGEs/RAGE axis as a risk for cardiovascular diseases in patients with renal failure.
  
  
  CONCLUSIONS
  AGEs/RAGE axis could be a crucial mediator of oxidative stress in renal failure. RAGE could be not only a useful biomarker, but also a potentially therapeutic target to overcome the accumulated adverse metabolic memory in renal failure.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan. hidekoyama@med.osaka-cu.ac.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D000375:Aging / Q000502:physiology; D050197:Atherosclerosis / Q000473:pathology; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic