ArticlePloS one2012
Chronic kidney disease-induced cardiac fibrosis is ameliorated by reducing circulating levels of a non-dialysable uremic toxin, indoxyl sulfate.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 3 of them syntheses that pooled it.
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
95 citing papers in PubMed, 3 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- Pooled it
- Animal Models for Studying Protein-Bound Uremic Toxin Removal-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Protein-bound uremic toxin lowering strategies in chronic kidney disease: a systematic review and meta-analysis.Journal of nephrology · 2021Pooled it
- The Heart-Kidney Axis in Heart Failure and Chronic Kidney Disease: Mechanisms, Mediators, and Therapeutic Implications.Biomolecules · 2026Review
- Microparticles at the crossroads of the gut-kidney axis: Mechanistic drivers and therapeutic horizons in hemodialysis.World journal of nephrology · 2026Review
- Review
- In vitro modeling of renal injury-induced cardiac effects using human iPSC-derived organoids.Cell communication and signaling : CCS · 2026Article
- Review
- Sex-specific cardiac dysfunction in mice with chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Observational
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
- Renal Denervation Improves Uremic Cardiomyopathy in Rats With Chronic Kidney Disease.Journal of the American Heart Association · 2025Article
- Gut-Heart Axis: The Role of Gut Microbiota and Metabolites in Heart Failure.Circulation research · 2025Review
- Colonization withbioRxiv : the preprint server for biology · 2025Article
- 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
- Review
- Acute kidney disease in mice is associated with early cardiovascular dysfunction.Renal failure · 2024Article
- Rat Models of Cardiorenal Syndrome and Methods for Functional Assessment.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The AKI-to-CKD Transition: The Role of Uremic Toxins.International journal of molecular sciences · 2023Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiovascular death commonly occurs in patients with chronic kidney disease. Indoxyl sulfate (IS), a uremic toxin, has been demonstrated in vitro as a contributory factor in cardiac fibrosis, a typical pathological finding in uremic cardiomyopathy. This study aimed to determine if cardiac fibrosis is reversible by lowering serum IS levels using an oral charcoal adsorbent, AST-120. Subtotal-nephrectomized (5/6-STNx) Sprague-Dawley rats were randomized to receive either AST-120 (AST-120, n=13) or no treatment (vehicle, n=17) for 12 weeks. Sham operated rats (n=12) were used as controls. Early left ventricular (LV) diastolic dysfunction was demonstrated by an increase in peak velocity of atrial filling [A and A' waves] and a decrease of E/A and E'/A' ratios obtained by echocardiography. This was accompanied by a 4.5-fold increase in serum IS (p<0.001) as well as elevated tail-cuff blood pressure (p<0.001) and heart weight (p<0.001). Increased LV fibrosis (p<0.001), gene expression of pro-fibrotic (TGF-β, CTGF) and hypertrophic (ANP, β-MHC and α-skeletal muscle actin) markers, as well as TGF-β and phosphorylated NF-κB protein expression were observed in STNx + vehicle rats. Treatment with AST-120 reduced serum creatinine (by 54%, p<0.05) and urine total protein (by 27%, p<0.05) vs vehicle whilst having no effect on blood pressure (AST-120=227 ± 11 vs vehicle =224 ± 8 mmHg, ns) and heart weight. The increase in serum IS was prevented with AST-120 (by 100%, p<0.001) which was accompanied by reduced LV fibrosis (68%, p<0.01) and TGF-β and phosphorylated NF-κB protein expression (back to sham levels, p<0.05) despite no significant change in LV function. In conclusion, STNx resulted in increased cardiac fibrosis and circulating IS levels. Reduction of IS with AST-120 normalizes cardiac fibrosis, in a blood pressure independent manner.
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Registered trials
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