Accelerated AGEing: The Impact of Advanced Glycation End Products on the Prognosis of Chronic Kidney Disease

Dozio, Elena; Caldiroli, Lara; Molinari, Paolo; Castellano, Giuseppe; Delfrate, Nicholas Walter; Romanelli, Massimiliano Marco Corsi; Vettoretti, Simone

doi:10.3390/antiox12030584

Cited by 19 publications

(8 citation statements)

References 166 publications

(181 reference statements)

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“…AGEs induce pathophysiological changes during the aging process [ 37 , 38 ]. AGEs are known aging products, and they participate in the onset and progress of chronic kidney disease [ 39 ]. Resveratrol has been suggested to have the potential to suppress the AGEs-related complications [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Alleviates Advanced Glycation End-Products-Related Renal Dysfunction in D-Galactose-Induced Aging Mice

et al. 2023

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The elderly have higher concentrations of advanced glycation end-products (AGEs). AGEs are considered risk factors that accelerate aging and cause diabetic nephropathy. The effects of AGEs on renal function in the elderly remain to be clarified. This study aimed to explore the role of AGEs in renal function decline in the elderly and the protective effect of resveratrol, a stilbenoid polyphenol, comparing it with aminoguanidine (an AGEs inhibitor). A D-galactose-induced aging mouse model was used to explore the role of AGEs in the process of renal aging. The mice were administered D-galactose subcutaneously for eight weeks in the presence or absence of orally administered aminoguanidine or resveratrol. The results showed that the serum levels of AGEs and renal function markers BUN, creatinine, and cystatin C in the mice significantly increased after the administration of D-galactose, and this outcome could be significantly reversed by treatment with aminoguanidine or resveratrol. The protein expression levels for apoptosis, fibrosis, and aging-related indicators in the kidneys were significantly increased, which could also be reversed by treatment with aminoguanidine or resveratrol. These findings suggest that resveratrol could alleviate AGEs-related renal dysfunction through the improvement of renal cellular senescence, apoptosis, and fibrosis in D-galactose-induced aging in mice.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Alleviates Advanced Glycation End-Products-Related Renal Dysfunction in D-Galactose-Induced Aging Mice

et al. 2023

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“…A rise in sRAGE levels has also been linked to a higher mortality risk in hemodialysis and peritoneal dialysis patients [ 55 ]. Significantly lower levels of sRAGE have been described in patients with hypercholesterolemia, hypertension, chronic obstructive pulmonary disease, Alzheimer’s disease, and vascular dementia [ 56 , 57 , 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

AI-Enhanced Predictive Modeling for Identifying Depression and Delirium in Cardiovascular Patients Scheduled for Cardiac Surgery

Nowakowska,

Sakellarios,

Kaźmierski

et al. 2023

Diagnostics

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Several studies have demonstrated a critical association between cardiovascular disease (CVD) and mental health, revealing that approximately one-third of individuals with CVD also experience depression. This comorbidity significantly increases the risk of cardiac complications and mortality, a risk that persists regardless of traditional factors. Addressing this issue, our study pioneers a straightforward, explainable, and data-driven pipeline for predicting depression in CVD patients. Methods: Our study was conducted at a cardiac surgical intensive care unit. A total of 224 participants who were scheduled for elective coronary artery bypass graft surgery (CABG) were enrolled in the study. Prior to surgery, each patient underwent psychiatric evaluation to identify major depressive disorder (MDD) based on the DSM-5 criteria. An advanced data curation workflow was applied to eliminate outliers and inconsistencies and improve data quality. An explainable AI-empowered pipeline was developed, where sophisticated machine learning techniques, including the AdaBoost, random forest, and XGBoost algorithms, were trained and tested on the curated data based on a stratified cross-validation approach. Results: Our findings identified a significant correlation between the biomarker “sRAGE” and depression (r = 0.32, p = 0.038). Among the applied models, the random forest classifier demonstrated superior accuracy in predicting depression, with notable scores in accuracy (0.62), sensitivity (0.71), specificity (0.53), and area under the curve (0.67). Conclusions: This study provides compelling evidence that depression in CVD patients, particularly those with elevated “sRAGE” levels, can be predicted with a 62% accuracy rate. Our AI-driven approach offers a promising way for early identification and intervention, potentially revolutionizing care strategies in this vulnerable population.

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“…In addition, after exogenous AGEs are ingested, these AGE-modified proteins can interfere with normal cell-matrix contacts or inhibit physiological cellular growth and intercellular contact that are necessary to maintain tissue integrity and normal function. Of note, AGEs tend to accumulate in the serum and kidney which leads to the progression of diabetic nephropathy, and in turn promotes impaired excretion of AGEs in the kidneys of healthy mice (Dozio et al, 2023). Bases on these studies above, we used serum and kidney fluorescence values of AGEs to reflect the accumulation of AGEs in serum and kidney at different AGEs intakes.…”

Section: Discussionmentioning

confidence: 99%

Effects of exogenous advanced glycation end products on oxidative stress and renal injury in healthy mice

Wen

Zhang

Xia

et al. 2023

eFood

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This study evaluated the biological effects of exogenous advanced glycation end products (AGEs) on the induction of chronic kidney disease and the dose‐effect relationship. Male C57BL/6 mice were placed on four diets, including saline and three other diets differing only in AGEs content (low‐AGEs [LA], medium‐AGEs [MA], and high‐AGEs [HA] ratio, 1:3:5) for 4 weeks. With the increasing intake of AGEs, mice developed a significant increase in blood glucose and lipid levels, the fluorescence intensity of AGEs, Nε‐(carboxymethyl)‐lysine, Nε‐(carboxyethyl)‐lysine, and malondialdehyde levels, whereas their superoxide dismutase activity and glutathione levels were decreased significantly. HA had the highest urinary protein levels and the lowest creatinine clearance compared to the other groups. These suggested that AGEs are an essential contributor to increasing oxidative stress levels and intake of high‐level AGEs induces more severe kidney function impairment. Meanwhile, the AGEs intake damaged the kidney structure in a dose‐dependent manner, as evidenced by granular degeneration of kidney tubular epithelial cells and inflammatory cell infiltration. These findings shed light on the detrimental impacts of AGEs on human kidneys, which also will help reveal a dose‐effect relationship of AGEs.

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Accelerated AGEing: The Impact of Advanced Glycation End Products on the Prognosis of Chronic Kidney Disease

Cited by 19 publications

References 166 publications

Resveratrol Alleviates Advanced Glycation End-Products-Related Renal Dysfunction in D-Galactose-Induced Aging Mice

Resveratrol Alleviates Advanced Glycation End-Products-Related Renal Dysfunction in D-Galactose-Induced Aging Mice

AI-Enhanced Predictive Modeling for Identifying Depression and Delirium in Cardiovascular Patients Scheduled for Cardiac Surgery

Effects of exogenous advanced glycation end products on oxidative stress and renal injury in healthy mice

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