Toxicity of uraemia—does it come of AGE?

In the course of normal ageing, and more markedly during hyperglycaemia, proteins are covalently modified and cross-linked through the generation of a family of related adducts which form slowly and irreversibly on most body proteins. Reducing sugars, e.g. glucose, interact with free amino groups to yield Schiff bases; in the course of days these are rearranged to form Amadori products. Over weeks such reversible products are slowly transformed into irreversibly crosslinked advanced glycosylation end-products (AGE); furoyl-furanyl-imidazole (FFI) has been claimed to be one of the cross-linking multifunctional groups, although doubts about its existence in vivo and the possibility of isolation artefacts persist. The acronym AGE was specifically chosen to indicate that a relation exists to the normal ageing process [1]. The AGE reaction depends on the availability of reducing sugars; hence the formation of AGE occurs at a faster rate in patients with diabetes mellitus.