ArticleJournal of the American Society of Nephrology : JASN2019
Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance.
Article in Journal of the American Society of Nephrology : JASN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
115 citing papers in PubMed, 4 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Chronic kidney disease increases the risks of age-related macular degeneration: a systematic review and meta-analysis.Frontiers in medicine · 2025Pooled it
- Animal Models for Studying Protein-Bound Uremic Toxin Removal-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Effects of Microbiota-Driven Therapy on Circulating Indoxyl Sulfate and P-Cresyl Sulfate in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Advances in nutrition (Bethesda, Md.) · 2022Pooled it
- Pooled it
- Trial
- Comparison of uremic toxin removal between expanded hemodialysis and high volume online hemodiafiltrations in different modes.Acta biochimica Polonica · 2024Trial
- Trial
- Cardiovascular-kidney-metabolic syndrome through the lens of gut‑derived uremic toxins.Gut microbes · 2026Review
- Combined Docosahexaenoic Acid and Captopril Treatment Attenuates Indole Acetic Acid Induced Cardiovascular Injury in Chronic Kidney Disease.Molecular nutrition & food research · 2026Article
- Indoxyl Sulfate Promotes Vascular Calcification in Association with Oxidative Stress and Activation of ERK and Wnt/β-Catenin Signaling Pathways.International journal of molecular sciences · 2026Article
- Review
- Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function.Nature microbiology · 2026Article
- The Role and Mechanism of Gut Microbiota and Metabolites in Vascular Calcification.International journal of molecular sciences · 2026Review
- Improving immune function and mitochondrial health in patients undergoing hemodialysis: benefits of combining high-flux dialysis with hemoperfusion.Frontiers in medicine · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Metabolic reprogramming in chronic kidney disease-cardiovascular disease comorbidity: from molecular mechanisms to therapeutic strategies.Frontiers in pharmacology · 2026Review
- Calciphylaxis diagnosis, management and future directions: a comprehensive update on behalf of the European Renal Association CKD-MBD Working Group.Clinical kidney journal · 2025Review
- Discovery of non-invasive biomarkers for accurate detection of membranous nephropathy.Scientific reports · 2025Article
- Serum P-Cresyl Sulfate Is Associated with Peripheral Arterial Stiffness in Chronic Hemodialysis Patients.Diagnostics (Basel, Switzerland) · 2025Article
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProtein-bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) have been associated with cardiovascular morbidity and mortality in patients with CKD. However, direct evidence for a role of these toxins in CKD-related vascular calcification has not been reported.
methodsTo study early and late vascular alterations by toxin exposure, we exposed CKD rats to vehicle, IS (150 mg/kg per day), or PCS (150 mg/kg per day) for either 4 days (short-term exposure) or 7 weeks (long-term exposure). We also performed unbiased proteomic analyses of arterial samples coupled to functional bioinformatic annotation analyses to investigate molecular signaling events associated with toxin-mediated arterial calcification.
resultsLong-term exposure to either toxin at serum levels similar to those experienced by patients with CKD significantly increased calcification in the aorta and peripheral arteries. Our analyses revealed an association between calcification events, acute-phase response signaling, and coagulation and glucometabolic signaling pathways, whereas escape from toxin-induced calcification was linked with liver X receptors and farnesoid X/liver X receptor signaling pathways. Additional metabolic linkage to these pathways revealed that IS and PCS exposure engendered a prodiabetic state evidenced by elevated resting glucose and reduced GLUT1 expression. Short-term exposure to IS and PCS (before calcification had been established) showed activation of inflammation and coagulation signaling pathways in the aorta, demonstrating that these signaling pathways are causally implicated in toxin-induced arterial calcification.
conclusionsIn CKD, both IS and PCS directly promote vascular calcification
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.