Skin autofluorescence, a marker for advanced glycation end product accumulation, is associated with arterial stiffness in patients with end-stage renal disease

Ueno, Hiroki; Koyama, Hideki; Tanaka, Shinji; Fukumoto, Shinya; Shinohara, K.; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawà, Yoshiki

doi:10.1016/j.metabol.2008.05.016

Cited by 87 publications

(88 citation statements)

References 30 publications

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“…Moreover, skin autofluorescence (a marker of AGE accumulation) is associated with arterial PWV (and therefore, arterial stiffness) in patients with ESRD. 126 This may be caused by the formation of irreversible crosslinks between the end products and long-lived structural proteins, such as collagen and elastin.…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Uremic Toxicity of Advanced Glycation End Products in CKD

Stinghen

Massy

Vlassara

et al. 2016

Journal of the American Society of Nephrology

195

175

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Advanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product-specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD.

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Section: Endothelial Dysfunctionmentioning

confidence: 99%

Uremic Toxicity of Advanced Glycation End Products in CKD

Stinghen

Massy

Vlassara

et al. 2016

Journal of the American Society of Nephrology

195

175

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“…Higher aPWV is reflective of AS. AGEs have been associated with an increase in aPWV in healthy individuals (Semba et al 2009), hypertensive individuals (McNulty et al 2007), subjects with end-stage renal failure (Ueno et al 2008) and patients with type 2 diabetes (Choi et al 2009). In type 1 diabetes, AGEs have been associated with an increase in pulse pressure, a surrogate marker for central AS (Schram et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Advanced glycation end products are associated with arterial stiffness in type 1 diabetes

Llauradó¹,

Ceperuelo-Mallafré²,

Vilardell³

et al. 2014

Journal of Endocrinology

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The aim of this study was to investigate the relationship between advanced glycation end products (AGEs) and arterial stiffness (AS) in subjects with type 1 diabetes without clinical cardiovascular events. A set of 68 patients with type 1 diabetes and 68 age-and sex-matched healthy subjects were evaluated. AGEs were assessed using serum concentrations of N-carboxymethyl-lysine (CML) and using skin autofluorescence. AS was assessed by aortic pulse wave velocity (aPWV), using applanation tonometry. Patients with type 1 diabetes had higher serum concentrations of CML (1.18 vs 0.96 mg/ml; PZ0.008) and higher levels of skin autofluorescence (2.10 vs 1.70; P!0.001) compared with controls. These differences remained significant after adjustment for classical cardiovascular risk factors. Skin autofluorescence was positively associated with aPWV in type 1 diabetes (rZ0.370; PZ0.003). No association was found between CML and aPWV. Skin autofluorescence was independently and significantly associated with aPWV in subjects with type 1 diabetes (bZ0.380; P!0.001) after adjustment for classical cardiovascular risk factors. Additional adjustments for HbA1c, disease duration, and low-grade inflammation did not change these results. In conclusion, skin accumulation of autofluorescent AGEs is associated with AS in subjects with type 1 diabetes and no previous cardiovascular events. These findings indicate that determination of tissue AGE accumulation may be a useful marker for AS in type 1 diabetes.

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“…Increased skin AF is associated with AGE accumulation and development of a range of vascular complications as well as allcause and cardiovascular mortality in people with diabetes (14)(15)(16)(17)(18). In people with end-stage kidney disease on dialysis, skin AF is associated with arterial stiffness (19). Skin AF is also independently associated with cardiovascular and all-cause mortality in hemodialysis patients (20,21).…”

Section: Introductionmentioning

confidence: 99%

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Fraser

Roderick

McIntyre

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied.Design, setting, participants, & measurements A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling for biochemistry, and measurement of skin autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality.Results In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P,0.001) on KaplanMeier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P,0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin.Conclusions Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD.

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Skin autofluorescence, a marker for advanced glycation end product accumulation, is associated with arterial stiffness in patients with end-stage renal disease

Cited by 87 publications

References 30 publications

Uremic Toxicity of Advanced Glycation End Products in CKD

Uremic Toxicity of Advanced Glycation End Products in CKD

Advanced glycation end products are associated with arterial stiffness in type 1 diabetes

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

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