Observational studyPloS one2015
Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.
Observational study in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Indoxyl sulfate in the gut-kidney axis: from diet-microbiome interactions to renal injury and targeted therapies.Frontiers in nutrition · 2026Review
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
- Nonatherosclerotic Cardiovascular Disease in Chronic Kidney Disease.Cardiology clinics · 2025Review
- Indoxyl Sulfate Induces Ventricular Arrhythmias Attenuated by Secretoneurin in Right Ventricular Outflow Tract Cardiomyocytes.Cardiovascular toxicology · 2025Article
- Benefits and Pitfalls of Uraemic Toxin Measurement in Peritoneal Dialysis.Journal of clinical medicine · 2025Review
- Indoxyl Sulfate-Induced Macrophage Toxicity and Therapeutic Strategies in Uremic Atherosclerosis.Toxins · 2024Review
- Indoxyl sulphate-initiated activation of cardiac fibroblasts is modulated by aryl hydrocarbon receptor and nuclear factor-erythroid-2-related factor 2.Journal of cellular and molecular medicine · 2024Article
- Impact of Impaired Kidney Function on Arrhythmia-Promoting Cardiac Ion Channel Regulation.International journal of molecular sciences · 2023Review
- Pro-Arrhythmic Potential of Accumulated Uremic Toxins Is Mediated via Vulnerability of Action Potential Repolarization.International journal of molecular sciences · 2023Article
- The Effects of Indoxyl Sulfate and Oxidative Stress on the Severity of Peripheral Nerve Dysfunction in Patients with Chronic Kidney Diseases.Antioxidants (Basel, Switzerland) · 2022Article
- Uremic toxins in chronic kidney disease highlight a fundamental gap in understanding their detrimental effects on cardiac electrophysiology and arrhythmogenesis.Acta physiologica (Oxford, England) · 2022Review
- Fibroblast growth factor 21 is associated with widening QRS complex and prolonged corrected QT interval in patients with stable angina.BMC cardiovascular disorders · 2022Article
- Chronic Kidney Disease Is Associated With Increased Cardiac Corin Expression But Decreased Proatrial Natriuretic Peptide Conversion Activity.Journal of the American Heart Association · 2022Article
- Review
- Indoxyl sulfate reduces Ito,f by activating ROS/MAPK and NF-κB signaling pathways.JCI insight · 2022Article
- The role of AMP-activated protein kinase α1-mediated endoplasmic reticulum stress in alleviating the toxic effect of uremic toxin indoxyl sulfate on vascular endothelial cells by Klotho.Journal of applied toxicology : JAT · 2021Article
- Fibroblast Growth Factor-23-Klotho Axis in Cardiorenal Syndrome: Mediators and Potential Therapeutic Targets.Frontiers in physiology · 2021Review
- Gut-Derived Protein-Bound Uremic Toxins.Toxins · 2020Review
- Improved cardiovascular autonomic function and decreased protein-bound uremic toxins in patients with end-stage renal disease after peritoneal dialysis.The Journal of international medical research · 2020Article
- The Arrhythmogenic Effect of Protein-Bound Uremic ToxinActa Cardiologica Sinica · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD). In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS) is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc) prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK) was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD) and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.
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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.