Indoxyl Sulfate, Not P-Cresyl Sulfate, is Associated with Advanced Glycation end Products in Patients on Long-Term Hemodialysis

Abstract

Background/Aims: Advanced glycation end products (AGEs) are pro-inflammatory and pro-oxidative compounds that play a critical role in endothelial dysfunction and atherosclerosis. Protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), inhibit endothelial function. We explored the association of IS and PCS with AGEs in a hemodialysis (HD) cohort. Methods: This study was a cross-sectional study that recruited 129 stable patients on maintenance HD in a single medical center from July 1 to July 15, 2011. Serum levels of total and free IS, PCS and AGEs were measured concurrently. General laboratory results and patient background were also investigated. Results: Serum levels of AGEs were associated with total IS (r = 2.7, p < 0.01) but not total PCS (r = 0.01, NS), free IS (r = 0.11, NS) or free PCS (r = 0.04, NS) using Pearson's analysis. Multiple linear regression analysis showed that total IS was significantly related to AGEs (β = 0.296, p < 0.01), free IS (β = 0.502, p < 0.01) and creatinine (β = 0.294, p < 0.01). Serum AGEs levels were also independently correlated with diabetes status (β = 0.250, p = 0.01) and total IS (β = 0.341, p < 0.01) concentrations after adjusting for other confounding variables. Moreover, patients with diabetes had higher serum AGEs levels than patients without diabetes (p < 0.01). Conclusions: These findings suggest that serum levels of total IS were associated with AGEs levels, which may participate in the process of atherosclerosis.

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease

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Non-Diabetic Kidney Disease in Type 2 Diabetic Patients: Prevalence, Clinical Predictors and Outcomes

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N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats

“…Although the first studies addressing AGEs-RAGE signaling had been focused on its participation in the development of diabetic nephropathy, growing evidence suggests that this signaling pathway may also participate in the pathogenesis of non-diabetic kidney diseases such as those associated with hypertension, obesity, sepsis and lupus [12][13][14]. Beyond that, genetic RAGE deletion or blockade with neutralizing antibodies was able to prevent the progression of a broad range of kidney diseases [15,16].…”