Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis

Wang, Chuncheng; Wang, Yao-Chang; Wang, Guei-Jane; Shen, Ming-Yi; Chang, Yen-Lin; Liou, Show-Yih; Chen, Hung-Chih; Chang, Chiz‐Tzung

doi:10.1371/journal.pone.0147771

Cited by 20 publications

(21 citation statements)

References 37 publications

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“…In addition, the AGEs contributed to the progression of kidney disease in non-diabetic nephropathy, the possible mechanisms for this included binding to the RAGE, inducing oxidative stress, endothelial dysfunction, inflammation, and podocyte injury [ 32 ]. Another study reported significant increases of AGEs in HD patients with cardiovascular diseases, compared with the non-CKD group [ 33 ]. This implied that the increased accumulation of AGEs in the subjects with uremia might have been because of the increased oxidative stress, rather than the increased glucose burden alone.…”

Section: Discussionmentioning

confidence: 99%

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients

2018

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The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD.

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Section: Discussionmentioning

confidence: 99%

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients

2018

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“…Cho et al proposed significantly higher skin AF in young adolescents of type 1 diabetes with retinopathy than those without retinopathy [ 18 ]. Higher skin AF associated with endothelial dysfunction [ 19 ] and arterial pulse wave velocity [ 20 ] has been described in subjects with end-stage renal failure. Recently, Sell et al proposed skin collagen fluorophore LW-1 to be a useful marker for the subclinical macrovascular disease in patients with type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Skin autofluorescence is associated with inappropriate left ventricular mass and diastolic dysfunction in subjects at risk for cardiovascular disease

Wang

et al. 2017

Cardiovasc Diabetol

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BackgroundEnhanced advanced glycation end products deposition within myocardial tissue may cause diastolic dysfunction. However, whether this is related to left ventricular hypertrophy or inappropriate left ventricular mass remains unclear.MethodsWe prospectively enrolled 139 subjects at risk for cardiovascular diseases. We used echocardiography for measurements of left ventricular mass and cardiac systolic and diastolic functional parameters. An advanced glycation end product reader was applied for measurements of skin autofluorescence values. Comparisons of left ventricular mass and echocardiographic parameters between the higher and lower skin autofluorescence groups were analyzed.ResultsCompared with the lower skin autofluorescence group, left ventricular mass index and the ratio of observed left ventricular mass/predicted left ventricular mass (oLVM/pLVM) was significantly higher in the higher skin autofluorescence group (61.22 ± 17.76 vs. 47.72 ± 11.62, P < 0.01, 1.62 ± 0.38 vs. 1.21 ± 0.21, P < 0.01). After adjustment for potential confounding factors, skin autofluorescence was an independent factor for left ventricular mass index (β = 0.32, P < 0.01) and the ratio of oLVM/pLVM (β = 0.41, P < 0.01). Skin autofluorescence ≥2.35 arbitrary unit predicted left ventricular hypertrophy at a sensitivity of 58.8%, and a specificity of 73.0% (P < 0.01). Skin autofluorescence ≥2.25 arbitrary unit predicted inappropriate left ventricular mass at a sensitivity of 71.1%, and a specificity of 83.9% (P < 0.01). Skin autofluorescence was positively correlated with E/E′, an indicator for diastolic dysfunction (r = 0.21, P = 0.01).ConclusionsSkin autofluorescence is a useful tool for detecting left ventricular hypertrophy, inappropriate left ventricular mass and diastolic dysfunction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0495-9) contains supplementary material, which is available to authorized users.

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“…When assessed using skin AF values, we observed a marked increase in vascular age, which is more than 10 years higher than the chronological age in patients with CKD. Vascular aging occurs along with endothelial dysfunction, vascular remodelling, inflammation, and increased stiffness, all of them previously associated with AGEs [ 16 , 38 ]. In this way, we observed a 3-fold increased risk of an atheromathous plaque in subjects with a skin AF value higher > 2.0 AU.…”

Section: Discussionmentioning

confidence: 99%

“…The progressive loss of glomerular filtration rate (GFR) is associated with systemic inflammation, as well as with an imbalance between oxygen reactive species production and antioxidant defenses [ 14 , 15 ]. Increased circulating levels of AGEs are found in patients with CKD undergoing hemodialysis regardless, of the presence of T2D [ 4 , 16 ]. Some additional factors have been associated with AGEs accumulation in renal failure because of decreased glomerular filtration, intraperitoneal formation during the time course of peritoneal dialysis, or dietary intake [ 17 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis

Cited by 20 publications

References 37 publications

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients

Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients

Skin autofluorescence is associated with inappropriate left ventricular mass and diastolic dysfunction in subjects at risk for cardiovascular disease

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

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