The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases.

Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, which may lead to an increase in the synthesis of advanced glycation end products (AGEs). Because AGEs are mostly removed by healthy kidneys, AGE accumulation is a result of both increased production and decreased kidney clearance. On the other hand, AGEs may potentially hasten decreasing kidney function in CKD patients, and are independently related to all-cause mortality. They are one of the non-traditional risk factors that play a significant role in the underlying processes that lead to excessive cardiovascular disease in CKD patients. When AGEs interact with their cell-bound receptor (RAGE), cell dysfunction is initiated by activating nuclear factor kappa-B (NF-κB), increasing the production and release of inflammatory cytokines. Alterations in the AGE-RAGE system have been related to the development of several chronic kidney diseases. Soluble RAGE (sRAGE) is a decoy receptor that suppresses membrane-bound RAGE activation and AGE-RAGE-related toxicity. sRAGE, and more specifically, the AGE/sRAGE ratio, may be promising tools for predicting the prognosis of kidney diseases. In the present review, we discuss the potential role of AGEs and sRAGE as biomarkers in different kidney pathologies.

Relationship between serum-soluble receptor for advanced glycation end products (sRAGE) and disease activity in rheumatoid arthritis patients.

Objective: Considering the important role of serum soluble receptor for advanced glycation end product (sRAGE/RAGE)-ligand system in rheumatoid arthritis (RA), this study aimed to evaluate serum sRAGE levels in RA patients compared to healthy subjects and to assess whether there is an association between sRAGE levels and disease characteristics in RA.Methods: In this cross-sectional study, 60 RA patients according to the ACR/EULAR 2010 criteria and 30 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and disease activity score 28 (DAS-28) measure of disease activity was assessed. Serum sRAGE level was measured using ELISA kit.Results: The mean ± SD age of patients and controls was 54.86 ± 11.65 and 50.71 ± 3.72 years, respectively). Serum sRAGE level was significantly higher in RA patients (median [25th and 75th percentiles], 1000.3 [792.00, 1486.8]) compared to healthy controls (median [25th and 75th percentiles], 293.25 [220.35, 364.24]) (p < .001). There was significant difference in serum sRAGE level according to the activity of disease (p < .001). There were significant positive correlations between serum sRAGE level with disease activity (r = 0.67, p < .001), ESR (r = 0.411, p = .001) and CRP (r = 0.273, p = .035). There were no significant correlations between serum sRAGE level with demographic characteristics as well as biochemical measurements including serum creatinine, BUN, RF, and Anti-CCP (p > .05).Conclusions: Our study revealed higher serum sRAGE levels in RA patients compared to healthy controls, which correlated positively with disease activity.

Oleic Acid Status Positively Correlates with the Soluble Receptor for Advanced Glycation End-Products (sRAGE) in Healthy Adults Who Are Homozygous for G Allele of RAGE G82S Polymorphism.

BACKGROUND: The soluble form of receptor for advanced glycation end products (sRAGE) have been implicated in the prevention of numerous pathologic states, and highlights as an attractive therapeutic target. Because diets rich in monounsaturated fatty acids (MUFA) reduce postprandial oxidative stress and inflammation that is related to better health during aging, we investigated the association between red blood cell (RBC) fatty acids with circulatory AGE biomarkers and further stratified this correlation based on GG and GA + AA genotype. METHODS: A total of 172 healthy participants (median age = 53.74 ± 0.61 years) were recruited for the study. RBC fatty acid was analysed using gas chromatography and sRAGE was measured using a commercial ELISA kit. RESULTS: The result showed a non-significant correlation between total MUFA with sRAGE however oleic acid (C18:1) exhibited a positive correlation (r = 0.178, p = 0.01) that remained statistically significant (ß = 0.178, p = 0.02) after a stepwise multivariate regression analysis after adjusting for age, BMI and gender. In a univariate analysis, a positive significant correlation between C18:1 and sRAGE in GG genotype (r = 0.169, p = 0.02) and a non-significant correlation with GA + AA genotype (r = 0.192, p = 0.21) was evident. When C18:1 was stratified, a significant difference was observed for oleic acid and G82S polymorphism: low C18:1/GA + AA versus high C18:1/GG (p = 0.015) and high C18:1/GA + AA versus high C18:1/GG (p = 0.02). CONCLUSION: Our study suggests that increased levels of C18:1 may be a potential therapeutic approach in increasing sRAGE in those with GG genotype and play a role in modulating AGE metabolism.