Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality;
hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called
uremic toxins. These include
advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between
proteins and
glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl)
glyoxal. AGE accumulate in tissue where they cross-link with
proteins, e.g.,
collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in
cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in
cardiovascular disease in
end stage renal disease (
ESRD). This review will also present the possibility of reducing the AGE accumulation in
ESRD patients using the following five methods: 1) use of low AGE
peritoneal dialysis solutions; 2) use of advanced
hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of
hemodialysis patients; and 5)
renal transplantation.