Association of Advanced Glycation End-product Accumulation and Adverse Outcomes in Peritoneal Dialysis and Haemodialysis Patients and the Impact of a Dietetic Intervention on Skin Autofluorescence

STUDY BACKGROUND

Chronic kidney disease (CKD) is a global public health problem and is associated with multiple adverse outcomes including reduced survival, especially in people requiring renal replacement therapy (peritoneal dialysis (PD), haemodialysis [HD] and transplantation). Multiple risk factors lead to the development and/or progression of CKD, such as obesity, hyperlipidaemia, glomerulonephritis, intercurrent infections, smoking, type 2 diabetes and hypertension, the two latter being considered as leading causes of CKD worldwide.

People on dialysis develop a variety of complications/abnormalities as a result of loss of endocrine or exocrine function of the kidneys, including anaemia, metabolic acidosis, bone and mineral disorders, fluid overload, hypertension, electrolyte disturbances and dyslipidaemia. In recent years, inflammation, oxidative stress and endothelial dysfunction (other common abnormalities in people on dialysis) have become areas of interest because of their strong relationship with higher rates of cardiovascular morbidity and mortality in people on dialysis.

Advanced glycation end-products (AGE) are uremic toxins that are markedly increased in people on dialysis. Formation of AGE starts with a non-enzymatic reaction between proteins and glucose molecules called the Maillard reaction; however, AGE are also formed more rapidly during oxidative stress with the subsequent formation of reactive carbonyl compounds like methyl glyoxal. At this point, AGE synthesis is irreversible and AGE will cross-link with tissue proteins; it seems that collagen in the skin and vascular basement membranes are especially susceptible to AGE accumulation and subsequent injury. AGE also interact with specific AGE receptors that will lead to the activation of systemic inflammation by increasing the release of cytokines and, consequently, exacerbate tissue damage. Importantly, AGE are also formed in food during cooking with dry heat at high temperatures such as in frying, grilling or roasting and about 10% of the ingested AGE is absorbed.

Skin autofluorescence (SAF) is a relatively new technique that measures the skin accumulation of AGE. It is a non-invasive, operator independent, quick (less than 5 minutes) and easy to perform technique that utilizes the fluorescent properties of AGE, like the extensively used collagen linked fluorescence (CLF) method, and has been validated with specific AGE measurements and CLF in skin biopsies. It has been reported that SAF is strongly correlated with overall and cardiovascular mortality in people with diabetes and undergoing HD. Several factors have been associated with higher SAF values in people on dialysis in cross-sectional studies, for instance, chronological age in both dialysis modalities, glucose exposure from peritoneal dialysis fluid and dialysis vintage only in people on PD and presence of diabetes in people on HD.