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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Role of AGEs in Diabetic Nephropathy

Author(s): Kei Fukami, Sho-ichi Yamagishi, Seiji Ueda and Seiya Okuda

Volume 14 , Issue 10 , 2008

Page: [946 - 952] Pages: 7

DOI: 10.2174/138161208784139710

Price: $65

Abstract

Diabetic nephropathy is the most common cause of end-stage renal disease in the world, and accounts for a significant increase in morbidity and mortality in patients with diabetes. Therapeutic options such as strict blood pressure and/or glycemic control are effective for preventing the development and progression of diabetic nephropathy, but the number of diabetic patients on hemodialysis is still increasing. Therefore, a novel therapeutic strategy that could halt the progression of diabetic nephropathy should be developed. Advanced glycation end products (AGEs) are heterogeneous cross-linked sugar-derived proteins which could accumulate in glomerular basement membrane, mesangial cells, endothelial cells, and podocytes in patients with diabetes and/or end-stage renal failure. AGEs are thought to be involved in the pathogenesis of diabetic nephropathy via multifactorial mechanisms such as oxidative stress generation and overproduction of various growth factors and cytokines. Further, recently, the cross-talk between AGEs and the renin-angiotensin system (RAS) has been proposed to participate in diabetic nephropathy. In addition, activation of the RAS elicits ROS generation and subsequently stimulates growth factor and cytokine production by kidney cells as well. These observations suggest that combination therapy with inhibitors of the RAS and blockers of the AGEs formation and/or their downstream pathway may be a novel therapeutic option for preventing diabetic nephropathy. In this paper, we review the role of AGEs and their receptor system in the pathogenesis of diabetic nephropathy. We further discuss here the cross-talk between AGEs and the RAS in the development and progression of diabetic nephropathy.

Keywords: Diabetic nephropathy, AGEs, RAGE, ROS, renin-angiotensin system, TGF-β


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