The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis

Lin, Cheng‐Jui; Pan, Chi-Feng; Liu, Hsuan‐Liang; Chen, Chuang; Jayakumar, Thanasekaran; Wang, Tuen-Jen; Chen, Han‐Hsiang; Wu, Chih‐Jen

doi:10.1016/j.atherosclerosis.2012.07.012

Cited by 57 publications

(43 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study showed that IS was independently related to pentosidine levels, and the results suggested that IS is involved in the pathogenesis of atherosclerosis. Recent studies also indicated that elevated IS and PCS levels are associated with more frequent vascular access failure and dysfunction in HD patients [28,29]. However, the present report is the first study …”

Section: Discussioncontrasting

confidence: 49%

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

Lin

Pan

et al. 2015

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 49%

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

Lin

Pan

et al. 2015

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Multivariable linear regression was performed to identify independent associations between dietary fiber, protein, the protein-fiber index and toxins after adjustment for other known predictors of toxins including kidney function (eGFR), gender and diabetes [18,19]. The likelihood ratio test was used to compare regression models and the Steiger's formula [20] was used to compare the strength of related correlation coefficients (r 2 ).…”

Section: Discussionmentioning

confidence: 99%

Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients

Rossi

Johnson

et al. 2015

Nutrition, Metabolism and Cardiovascular Diseases

123

View full text Add to dashboard Cite

“…In hemodialyzed patients, the KYN/TRP ratio is positively associated with thrombosis markers [75], and IS level correlates with vascular access intervention [104]. In CKD patients, the levels of the indolic uremic toxins IS and IAA correlate with the levels and activity of tissue factor [30], the main initiator of the blood coagulation cascade.…”

Section: Involvement Of Ahr-activating Uremic Toxins In Thrombosismentioning

confidence: 99%

The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

Sallée

Dou

Cérini

et al. 2014

Toxins

208

178

View full text Add to dashboard Cite

Patients with chronic kidney disease (CKD) have a higher risk of cardiovascular diseases and suffer from accelerated atherosclerosis. CKD patients are permanently exposed to uremic toxins, making them good candidates as pathogenic agents. We focus here on uremic toxins from tryptophan metabolism because of their potential involvement in cardiovascular toxicity: indolic uremic toxins (indoxyl sulfate, indole-3 acetic acid, and indoxyl-β-d-glucuronide) and uremic toxins from the kynurenine pathway (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and quinolinic acid). Uremic toxins derived from tryptophan are endogenous ligands of the transcription factor aryl hydrocarbon receptor (AhR). AhR, also known as the dioxin receptor, interacts with various regulatory and signaling proteins, including protein kinases and phosphatases, and Nuclear Factor-Kappa-B. AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and some polychlorinated biphenyls is associated with an increase in cardiovascular disease in humans and in mice. In addition, this AhR activation mediates cardiotoxicity, vascular inflammation, and a procoagulant and prooxidant phenotype of vascular cells. Uremic toxins derived from tryptophan have prooxidant, proinflammatory, procoagulant, and pro-apoptotic effects on cells involved in the cardiovascular system, and some of them are related with cardiovascular complications in CKD. We discuss here how the cardiovascular effects of these uremic toxins could be mediated by AhR activation, in a “dioxin-like” effect.

show abstract

The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis

Cited by 57 publications

References 31 publications

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

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

Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients

The Aryl Hydrocarbon Receptor-Activating Effect of Uremic Toxins from Tryptophan Metabolism: A New Concept to Understand Cardiovascular Complications of Chronic Kidney Disease

Contact Info

Product

Resources

About