ArticleCritical care (London, England)2014
Renal effects of treatment with a TLR4 inhibitor in conscious septic sheep.
Article in Critical care (London, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Research hotspots and future trends in sepsis-associated acute kidney injury: a bibliometric and visualization analysis.Frontiers in medicine · 2024Pooled it
- Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study.Critical care (London, England) · 2022Trial
- Exploring the mechanism of polymorphonuclear neutrophils against sepsis based on immune model.Annals of medicine · 2026Review
- Comparative Analysis of Intestinal TLR4 Gene Expression and Functional Verification in Lepus yarkandensis and Oryctolagus cuniculus.Biochemical genetics · 2025Article
- Plasma expansion and renal perfusion in critical COVID-19 with AKI: A prospective case control study.Acta anaesthesiologica Scandinavica · 2025Article
- Sepsis-Associated Acute Kidney Injury: What's New Regarding Its Diagnostics and Therapeutics?Diagnostics (Basel, Switzerland) · 2024Review
- TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway.Renal failure · 2024Article
- Dexmedetomidine ameliorates acute kidney injury by regulating mitochondrial dynamics via the α2-AR/SIRT1/PGC-1α pathway activation in rats.Molecular medicine (Cambridge, Mass.) · 2024Article
- Vitamin C as a treatment for organ failure in sepsis.European journal of medical research · 2023Review
- Toll-like Receptor 4 in Acute Kidney Injury.International journal of molecular sciences · 2023Review
- Role of Toll-like receptor 4 in intravascular hemolysis-mediated injury.The Journal of pathology · 2022Article
- Ibrutinib does not prevent kidney fibrosis following acute and chronic injury.Scientific reports · 2021Article
- Review
- Toll-Like Receptors in Acute Kidney Injury.International journal of molecular sciences · 2021Review
- The Correlation Between the Types of Initial Bacterial Infection and Clinical Prognosis in Patients With Septic AKI.Frontiers in medicine · 2021Article
- Current Status of Septic Cardiomyopathy: Basic Science and Clinical Progress.Frontiers in pharmacology · 2020Review
- High mobility group box protein 1 neutralization therapy in ovine bacteremia: Lessons learned from an ovine septic shock model incorporating intensive care support.Experimental and therapeutic medicine · 2019Article
- LPS-Binding Protein Modulates Acute Renal Fibrosis by Inducing Pericyte-to-Myofibroblast Trans-Differentiation through TLR-4 Signaling.International journal of molecular sciences · 2019Article
- miR-146a targeted to splenic macrophages prevents sepsis-induced multiple organ injury.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Role of TLR4 signaling in the nephrotoxicity of heme and heme proteins.American journal of physiology. Renal physiology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAcute kidney injury (AKI) is a common and feared complication of sepsis. The pathogenesis of sepsis-induced AKI is largely unknown, and therapeutic interventions are mainly supportive. In the present study, we tested the hypothesis that pharmacological inhibition of Toll-like receptor 4 (TLR4) would improve renal function and reduce renal damage in experimental sepsis, even after AKI had already developed.
methodsSheep were surgically instrumented and subjected to a 36-hour intravenous infusion of live Escherichia coli. After 12 hours, they were randomized to treatment with a selective TLR4 inhibitor (TAK-242) or vehicle.
resultsThe E. coli caused normotensive sepsis characterized by fever, increased cardiac index, hyperlactemia, oliguria, and decreased creatinine clearance. TAK-242 significantly improved creatinine clearance and urine output. The increase in N-acetyl-beta-D-glucosaminidas, a marker of tubular damage, was attenuated. Furthermore, TAK-242 reduced the renal neutrophil accumulation and glomerular endothelial swelling caused by sepsis. These effects were independent of changes in renal artery blood flow and renal microvascular perfusion in both cortex and medulla. TAK-242 had no effect per se on the measured parameters.
conclusionsThese results show that treatment with a TLR4 inhibitor is able to reverse a manifest impairment in renal function caused by sepsis. In addition, the results provide evidence that the mechanism underlying the effect of TAK-242 on renal function does not involve improved macro-circulation or micro-circulation, enhanced renal oxygen delivery, or attenuation of tubular necrosis. TLR4-mediated inflammation resulting in glomerular endothelial swelling may be an important part of the pathogenesis underlying Gram-negative septic acute kidney injury.
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Registered trials
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.