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.