AGE/RAGE in diabetic kidney disease and ageing kidney

Abstract

Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease that inevitably progress to end-stage kidney disease. Intervention strategies such as blood glucose control is effective for preventing DKD, but many patients with DKD still reach end-stage kidney disease. Although comprehensive mechanisms shed light on the progression of DKD, the most compelling evidence has highlighted that hyperglycemia-related advanced glycation end products (AGEs) formation plays a central role in the pathogenesis of DKD. Pathologically, accumulation of AGEs-mediated receptor for AGEs (RAGE) triggers oxidative stress and inflammation, which is the major deleterious effect of AGEs in host and intestinal microenvironment of diabetic and ageing conditions. The activation of AGEs-mediated RAGE could evoke nicotinamide adenine dinucleotide phosphate oxidase-induced reactive oxygen and nitrogen species production and subsequently give rise to oxidative stress in DKD and ageing kidney. Therefore, targeting RAGE with its ligands mediated oxidative stress and chronic inflammation is considered as an additional intervention strategy for DKD and ageing kidney. In this review, we summarize AGEs/RAGE-mediated oxidative stress and inflammation signaling pathways in DKD and ageing kidney, discussing opportunities and challenges of targeting at AGEs/RAGE-induced oxidative stress that could hold the promising potential approach for improving DKD and ageing kidney.

Keywords: Advanced glycation end products; Ageing kidney; Diabetic kidney disease; Oxidative stress and inflammation; RAGE.