Advanced Glycation End Products (AGEs) and Chronic Kidney Disease: Does the Modern Diet AGE the Kidney?

Since the 1980s, chronic kidney disease (CKD) affecting all ages has increased by almost 25%. This increase may be partially attributable to lifestyle changes and increased global consumption of a western diet, which is typically energy dense, low in fruits and vegetables, and high in animal protein and ultra-processed foods. These modern food trends have led to an increase in the consumption of advanced glycation end products (AGEs) in conjunction with increased metabolic dysfunction, obesity and diabetes, which facilitates production of endogenous AGEs within the body. When in excess, AGEs can be pathological via both receptor-mediated and non-receptor-mediated pathways. The kidney, as a major site for AGE clearance, is particularly vulnerable to AGE-mediated damage and increases in circulating AGEs align with risk of CKD and all-cause mortality. Furthermore, individuals with significant loss of renal function show increased AGE burden, particularly with uraemia, and there is some evidence that AGE lowering via diet or pharmacological inhibition may be beneficial for CKD. This review discusses the pathways that drive AGE formation and regulation within the body. This includes AGE receptor interactions and pathways of AGE-mediated pathology with a focus on the contribution of diet on endogenous AGE production and dietary AGE consumption to these processes. We then analyse the contribution of AGEs to kidney disease, the evidence for dietary AGEs and endogenously produced AGEs in driving pathogenesis in diabetic and non-diabetic kidney disease and the potential for AGE targeted therapies in kidney disease.

Automated summary

Since the 1980s, the incidence of chronic kidney disease (CKD) has increased by almost 25%. This is partly due to changes in lifestyle and the global consumption of a western diet, which is high in energy, low in fruits and vegetables, and rich in animal protein and processed foods. These dietary trends have led to an increase in the consumption of advanced glycation end products (AGEs) and metabolic disorders, obesity, and diabetes, which contribute to the production of endogenous AGEs in the body. Excessive accumulation of AGEs can be pathologic through receptor-mediated and non-receptor-mediated pathways. AGEs are cleared by the kidneys, making them particularly susceptible to AGE-mediated damage, and high levels of circulating AGEs are associated with an increased risk of CKD and all-cause mortality. Individuals with significant loss of renal function have increased AGE burden, particularly in those with uremia, and there is evidence that lowering AGEs through diet or pharmacological inhibition may be beneficial for CKD. This review explores the pathways of AGE formation and regulation in the body, the impact of diet on endogenous AGE production and dietary AGE consumption, the contribution of AGEs to kidney disease, and the potential of AGE-targeted therapies for kidney disease.