Glycation in diabetic nephropathy

The kidney is an extremely complex organ with broad ranging functions in the body, including but not restricted to waste excretion, ion and water balance, maintenance of blood pressure, glucose homeostasis, generation of erythropoietin and activation of vitamin D. With diabetes, many of these integral processes are interrupted via a combination of haemodynamic and metabolic changes including increases in the accumulation of proteins modified by advanced glycation, known as advanced glycation end products (AGEs). Indeed, hyperglycaemia and the redox imbalances seen with diabetes are each independent accelerants for the production of AGEs, which synergistically combine in this disorder. In addition, as kidney function declines, characterised by a loss of glomerular filtration, the excretion of AGEs is decreased, possibly exacerbating renal injury by further elevating the body's tissue and circulating AGE pool. Therefore, it has become apparent that decreasing the accumulation of AGEs or interrupting their downstream effects on the kidney, are desirable therapeutic targets for the treatment of diabetic renal disease.