title: Uremic Toxicity of Advanced Glycation End Products in CKD.
abstract: Advanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product-specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD.
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) U-1088, Jules Verne University of Picardie, Amiens, France;
authors: Andréa E M
authors: AE
authors: Stinghen
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) U-1088, Jules Verne University of Picardie, Amiens, France; Division of Nephrology, Ambroise Paré University Medical Center, Assistance Publique-Hôpitaux de Paris (APHP), University of Paris Ouest, University Versailles-Saint Quentin, Boulogne Billancourt/Paris, France;
authors: Ziad A
authors: ZA
authors: Massy
authors: Division of Experimental Diabetes and Aging, Departments of Geriatrics and Palliative Care and Medicine and Division of Experimental Diabetes and Aging, Department of Geriatrics and Aging and Division of Nephrology, Department of Medicine, Icahn School of Medicine, New York, New York; and.
authors: Helen
authors: H
authors: Vlassara
authors: Division of Experimental Diabetes and Aging, Departments of Geriatrics and Palliative Care and Medicine and Division of Experimental Diabetes and Aging, Department of Geriatrics and Aging and Division of Nephrology, Department of Medicine, Icahn School of Medicine, New York, New York; and.
authors: Gary E
authors: GE
authors: Striker
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) U-1088, Jules Verne University of Picardie, Amiens, France; Biochemistry Laboratory, Amiens University Medical Center, Amiens, France agnes.boullier@u-picardie.fr.
authors: Agnès
authors: A
authors: Boullier
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D018384:Oxidative Stress; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism*; D014511:Uremia / Q000139:chemically induced* / Q000150:complications* / Q000628:therapy
chemical_list: D017127:Glycation End Products, Advanced
keywords: CKD; advanced glycation end product; uremia