Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women

Semba, Richard D.; Ferrucci, Luigi; Fink, Jeffrey C.; Sun, Kai; Beck, Justine; Dalal, Mansi; Guralnik, Jack M.; Fried, Linda P.

doi:10.1053/j.ajkd.2008.06.018

Cited by 64 publications

(53 citation statements)

References 54 publications

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“…A similar phenomenon has been demonstrated for hsCRP, leading to the suggestion that increased hsCRP concentrations are a marker of atherogenic processes [33]. In the same way, it is possible to hypothesise that the positive association of sRAGE with all-cause mortality observed in our study may indirectly reflect the overactivity of the AGE-RAGE axis in diabetic patients [11,34], which may not only accelerate the development and progression of vascular complications but also lead to the auto-induction of the production of RAGE and subsequent increased shedding of sRAGE into the circulation.…”

Section: Discussionsupporting

confidence: 87%

“…For example, we have previously shown that increased plasma adiponectin concentrations are associated with mortality in type 1 diabetes [20], whereas in patients with type 2 diabetes and the general population the relationship is the opposite [17,39]. In addition, none of these reports adjusted for the potentially confounding effects of renal function, which is a major determinant of sRAGE concentrations in individuals with type 2 diabetes [10,15,40,41] and in the general community [11]. The association between sRAGE and renal impairment partly represents the impaired renal clearance of AGEs and other RAGE ligands and may lead to increased tissue RAGE levels and/or sRAGE shedding.…”

Section: Discussionmentioning

confidence: 99%

“…sRAGE concentrations are positively correlated with circulating AGEs in patients with diabetes. In addition, sRAGE concentrations are influenced by body mass [8], drug treatment [9] and kidney function [10,11]. sRAGE production is also partly under genetic control, with a number of small studies showing an association between sRAGE and polymorphisms of AGER that codes for RAGE [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes

et al. 2011

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Aims/hypothesis Activation of the receptor for AGE (RAGE) is implicated in the development and progression of vascular complications of diabetes. In this study, we explore factors and mortality outcomes associated with soluble RAGE (sRAGE) in a multicentre nationwide cohort of Finnish adults with type 1 diabetes. Methods Baseline sRAGE concentrations were estimated in 3,100 adults with type 1 diabetes. Clinical and biological variables independently associated with sRAGE were identified using multivariate regression analysis. Independent predictors of mortality were determined using Cox and FineGray proportional-hazards models. Results The main independent determinants of sRAGE concentrations were estimated glomerular filtration rate, albuminuria, body mass index, age, duration of diabetes, HbA 1c and insulin dose (all p<0.05). During a median of 9.1 years of follow-up there were 202 deaths (7.4 per 1,000 patient years). sRAGE was independently associated with all-cause (Cox model: HR 1.03) and cardiovascular mortality (Fine-Gray competing risks model: HR 1.06) such that patients with the highest sRAGE concentrations had the greatest risk of mortality, after adjusting for age, sex, macrovascular disease, HDL-cholesterol, HbA 1c , triacylglycerol, high-sensitivity C-reactive protein (hsCRP) and the presence and severity of chronic kidney disease. Although polymorphisms in the gene coding for RAGE were significantly associated with sRAGE concentrations, none were associated with mortality outcomes. Conclusions/interpretation Increased concentrations of sRAGE are associated with increased all-cause and cardiovascular mortality in type 1 diabetes, potentially reflecting the activation and production of RAGE in the context of accelerated vascular disease. These novel findings highlight the importance of the RAGE activation in the prevention and management of diabetic complications.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes

et al. 2011

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“…In older community dwelling women, both esRAGE and sRAGE were found to be predictive of CVD mortality [68]. In a cross-sectional analysis of hypertensive patients, serum sRAGE correlated with systolic blood pressure [69].…”

Section: Discussionmentioning

confidence: 99%

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Sourris

Lyons

Dougherty

et al. 2014

Clinical Chemistry and Laboratory Medicine

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Background: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals. Methods: We measured body mass index (BMI), waistto-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carbo xymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC). Results: Plasma CML concentrations were related to diastolic blood pressure (r = −0.51, p < 0.01) independently of age, sex, BMI and WHR (p < 0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r = 0.47, p < 0.01) before and after adjustment for age, sex, BMI and WHR (p < 0.05). Plasma CML concentrations were related to the pulse pressure before (r = 0.42; p < 0.05) and after adjustment for age, sex, BMI and waist (p < 0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p = ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p = ns). Conclusions: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

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“…12-15 Advanced glycation end products, DAMPs that bind to RAGE rather than TLRs, are increased in renal failure and are involved in the progression of CKD in diabetic and nondiabetic kidney disease. 97,98 Acute Kidney Injury Acute kidney injury (AKI) results most commonly from IR, and although there are many causes, a common pathway leading to proximal tubule injury is activation of innate and adaptive immunity leading to inflammation. 99 Injury elicits release of pro-inflammatory DAMPs, 107 High concentrations of uric acid accumulate in ischemic tissues and precipitate to form monosodium urate crystals that elicit an immune response.…”

Section: Damps and Kidney Diseasementioning

confidence: 99%

Dangers Within

Rosin¹,

Okusa²

2011

Journal of the American Society of Nephrology

243

185

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Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women

Abstract: Background-Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of renal disease but their relation with level of kidney function has not been well characterized.

Cited by 64 publications

References 54 publications

Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes

Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure

Dangers Within

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