Abstract
Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, p<0.001). A skin AF value >2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4–6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, p<0.001) and LDL-cholesterol (r = -0.269, p = 0.001), and positively correlated with age (r = 0.472, p<0.001), pulse pressure (r = 0.238, p = 0.002), and SCORE risk (r = 0.451, p<0.001). A stepwise multivariate regression analysis showed that age and glomerular filtration rate independently predicted skin AF (R2 = 0.289, p<0.001). Skin AF is elevated in patients with mild-to-moderate CKD compared with control subjects. This finding may be independently associated with the glomerular filtration rate and the presence of subclinical atheromatous disease. Therefore, the use of skin AF may help to accurately evaluate the real cardiovascular risk at the early stages of CKD.
Highlights
Advanced glycation end products (AGEs) characterize a heterogeneous group of compounds formed by the non-enzymatic glycation of proteins after exposure to aldose sugars [1]
Skin AF has been previously validated in clinical settings, and its clinical value has been established in large studies including individuals with a high risk of atherosclerosis, as type 2 diabetes (T2D) and chronic kidney disease (CKD) [9,10,11,12]
To the best of our knowledge, this is the first study to show that subjects with early stages of CKD significantly increase skin AF values
Summary
Advanced glycation end products (AGEs) characterize a heterogeneous group of compounds formed by the non-enzymatic glycation of proteins after exposure to aldose sugars [1]. These reactions progress in normal aging, and are accelerated under chronic hyperglycemia [2, 3]. In this way, the concentration of AGEs is associated with a higher incidence and faster progression of chronic type 2 diabetes (T2D) microangiopathy, and it is an independent predictor of mortality in this population [4, 5]. AGEs promote the development and evolution of atherosclerosis through direct and receptor pathways [13]
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