Skin Autofluorescence and Subclinical Atherosclerosis in Mild to Moderate Chronic Kidney Disease: A Case-Control Study

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.

Advanced glycation end products (AGEs) estimated by skin autofluorescence are related with cardiovascular risk in renal transplant

“…Using a validated equation based on reference SAF values [ 23 ], we observed a marked increase in the vascular age of our patients (more than 30 years higher than chronological age). This disparity has also been documented in a recent research of Sanchez et al within CKD population with subclinical atherosclerosis [ 27 ].…”

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study

“…In a mixed study population of persons with predialysis CKD stage 5 or receiving HD and PD, higher SAF predicted ACM in a multivariable analysis that included traditional Framingham risk factors but was no longer significant after the addition of previous CVD, C reactive protein (CRP), and serum albumin [ 17 ]. In persons with earlier stages of CKD, higher SAF has been associated with several aspects of CVD including coronary artery calcification [ 18 ], subclinical atherosclerosis [ 19 ], and arterial stiffness [ 8 ]. Similarly, previous analyses from the RRID cohort reported independent associations between higher SAF and multiple cardiovascular risk factors including older age, male sex, diabetes, past history of CVD, smoking status, lower eGFR, higher urine protein to creatinine ratio, lower haemoglobin, and lower socioeconomic status [ 8 ].…”

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

“…AGEs increase with aging and their formation has been related to the level of carbohydrates; so, they have been linked to diabetes and obesity [ 207 ], as well as other diseases including atherosclerosis, Alzheimer's disease, and renal insufficiency [ 208 , 209 ]. Mass spectrometry-based techniques represent a key method in identifying protein adducts and the specific site of modification but their use is still limited in routine clinical analysis [ 210 , 211 ].…”