Skin Autofluorescence Associates With Vascular Calcification in Chronic Kidney Disease

Abstract

Objective— This study aims to evaluate the relationship between tissue advanced glycation end products, as reflected by skin autofluorescence, and vascular calcification in chronic kidney disease. Approach and Results— Three hundred patients with stage 3 to 5 chronic kidney disease underwent multislice computed tomography to estimate total coronary artery calcium score (CACS) and had tissue advanced glycation end product assessed using a skin autofluorescence reader. Intact parathyroid hormone ( P <0.001) displaced estimated glomerular filtration rate as third most significant factor associated with skin autofluorescence after age ( P <0.001) and diabetes mellitus ( P <0.001) in multiple regression analysis. On univariate multinomial logistic regression analysis, every 1-U increase in skin autofluorescence was associated with a 7.43-fold (95% confidence intervals, 3.59–15.37; P <0.001) increased odds of having CACS ≥400 compared with those with zero CACS. Skin autofluorescence retained significance in predicting CACS ≥400 (odds ratio, 3.63; 95% confidence intervals, 1.44–9.18; P =0.006) when adjusting for age, sex, serum calcium, phosphate, albumin, C-reactive protein, lipids, blood pressure, estimated glomerular filtration rate, and intact parathyroid hormone but marginally lost significance when additionally adjusting for diabetes mellitus (odds ratio, 2.23; 95% confidence intervals, 0.81–6.14; P =0.1). Combination of diabetes mellitus and higher intact parathyroid hormone was associated with greater skin autofluorescence and CACS versus those without diabetes mellitus and having lower intact parathyroid hormone. Conclusions— Tissue advanced glycation end product, as reflected by skin autofluorescence, showed a significant novel association with vascular calcification in chronic kidney disease. These data suggest that increased tissue advanced glycation end product may contribute to vascular calcification in chronic kidney disease and diabetes mellitus and warrant further experimental investigation.

Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

“…The relationship between coronary artery calcification and skin AF was also examined in Caucasian subjects with type 1 diabetes 18) and nondiabetes 30) . Several studies of Asian populations have identified associations of skin AF with markers of atherosclerosis, including coronary artery calcification in CKD subjects 31) . Furthermore, the associations of skin AF with the presence of CVD 32) and cardiovascular mortality 33) were also examined mainly in patients with CKD.…”

“…The most important aspect of this study is that several surrogate markers, such as carotid IMT, PWV, and CACS, widely used in daily practice, were comparatively assessed to demonstrate the significance of skin AF for the evaluation of atherosclerosis in a Japanese population. Previously, the relationships between skin AF and CACS were only reported in a European population with a small number of diabetic subjects 30) , American subjects with type 1 diabetes 18) and Chinese subjects with CKD 31) . Furthermore, the relationships between skin AF and IMT were assessed in European nondiabetic subjects 29) and Japanese CKD subjects 35) .…”

“…Second, the instrument used, the AGE reader, cannot be applied to subjects with dark skin because of the high absorption grade of the excited light. To address this problem, we excluded patients with skin reflectance below 6% in accordance with a recent report on a non-Caucasian population 31) . Although Meerwaldt et al demonstrated significant correlations of skin AF with tissue levels of N ε -(carboxymethyl) lysine, N ε -(carboxyethyl) lysine, and pentosidine 14, 41) , we did not directly perform histological examinations of skin accumulation of AGE in our subjects.…”

Bidirectional Translation in Cardiovascular Calcification

“…CKD patients are also prone to develop VC due in part to systemic and local aberrations in mineral homeostasis, with the former being a measurable biomarker and potential therapeutic target in this population 50 . Finally, advanced glycation end products (AGEs) can accumulate in CKD patients, which can be visualized non-invasively via skin autofluorescence and correlate with VC in CKD 51 .…”

A Comparative Study on Skin and Plasma Advanced Glycation End Products and Their Associations with Arterial Stiffness

“…Recent studies with this device measurement alone suggested that skin autofluorescence was associated with intermediate [15,16,17] and clinical cardiovascular outcomes [18,19]. However, the device-based skin autofluorescence and biochemical plasma measurements of AGEs have been rarely investigated simultaneously for their clinical relevance with regard to associations with known cardiovascular risk factors and arterial stiffness [20].…”