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Review, Journal: Intestinal Chelators, Sorbants, and Gut-Derived Uremic Toxins. (Pubmed Central) - Jul 3, 2021 Furthermore, AST-120 is an orally administered activated charcoal adsorbent that is widely used in Asian countries to specifically decrease uremic toxin levels. In this narrative review, we examine the latest data on the use of oral nonspecific and specific intestinal chelators to reduce levels of gut-derived uremic toxins.
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Review, Journal: Chronic Antibiotic-Refractory Pouchitis: Management Challenges. (Pubmed Central) - Jun 25, 2021 The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.
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Review, Journal: Targeting Uremic Toxins to Prevent Peripheral Vascular Complications in Chronic Kidney Disease. (Pubmed Central) - Jun 24, 2021 Moreover, growing evidence has shown the promising role of uremic toxins as a therapeutic target for PVD in CKD. This review focused on uremic toxins in the pathophysiology, in vitro and animal models, and current novel clinical approaches in reducing the uremic toxin to prevent peripheral vascular complications in CKD patients.
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Journal: Indoxyl sulfate induces intestinal barrier injury through IRF1-DRP1 axis-mediated mitophagy impairment. (Pubmed Central) - May 4, 2021 Administration of AST-120 or genetic knockout of IRF1 attenuated IS-induced DRP1 reduction, mitophagic impairment and intestinal barrier injury in mice. These findings suggest that reducing IS accumulation or targeting the IRF1-DRP1 axis may be a promising therapeutic strategy for alleviating CKD-associated intestinal dysfunction.
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Journal: Indoxyl Sulfate Contributes to Adipose Tissue Inflammation through the Activation of NADPH Oxidase. (Pubmed Central) - Mar 9, 2021 Using 5/6-nephrectomized mice, the administration of AST-120 suppressed oxidative stress and the expression of MCP-1, F4/80 and TNF-α in epididymal adipose tissue. These collective data suggest IS could be a therapeutic target for the CKD-related inflammatory response in adipose tissue, and that AST-120 could be useful for the treatment of IS-induced adipose tissue inflammation.
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Review, Journal: Indoxyl Sulfate, a Uremic Endotheliotoxin. (Pubmed Central) - Mar 3, 2021 IS reduction by AST-120 reverse these abnormalities...Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients.
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Journal: Oral Charcoal Adsorbents Attenuate Neointima Formation of Arteriovenous Fistulas. (Pubmed Central) - Mar 3, 2021 Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.
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Journal: TRPV1 Hyperfunction Involved in Uremic Toxin Indoxyl Sulfate-Mediated Renal Tubular Damage. (Pubmed Central) - Feb 26, 2021 These results clearly indicated that IS activated AhR and then upregulated ALOX12, and this induced endovanilloid 12(S)-HETE synthesis and contributed to TRPV1 hyperfunction in IS-treated tubular cells. Further study on TRPV1 may attenuate kidney susceptibility to the functional loss of end-stage kidney disease via IS.
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Trial completion, Trial completion date, Trial primary completion date: RECOVERY: Role of AST120 for Sarcopenia Prevention in Pre-dialysis Chronic Kidney Disease (clinicaltrials.gov) - Dec 17, 2020 P4, N=150, Completed, It is necessary to validate the renal protective effect of AST-120, as expected from the basic study on IS, including more patients with slowly progressive CKD in a large-scale clinical study in the future. Active, not recruiting --> Completed | Trial completion date: Dec 2020 --> Jul 2020 | Trial primary completion date: Dec 2020 --> Jul 2020
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Journal: Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition. (Pubmed Central) - Nov 6, 2020 Especially, AST-120 reduced the abundance of Erysipelotrichaceae uncultured and Clostridium sensu stricto 1, which have a gene involved in p-cresol production. Our findings suggest that, in addition to the adsorption of the uremic toxin precursors, AST-120 affects the abundance of some gut microbiota in normal and renal failure conditions, thereby explaining the different attenuation effects on IS and pCS.
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Review, Journal: Uremic Toxins and Atrial Fibrillation: Mechanisms and Therapeutic Implications. (Pubmed Central) - Oct 22, 2020 We have recently reported that patients with a higher serum IS level exhibit a higher rate of AF recurrence after catheter ablation, with serum IS being a significant predictor of AF recurrence. In this review, we discuss the possible mechanisms behind the AF-promoting effects of uremic toxins and summarize the reported clinical studies of uremic toxin-induced AF.
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Indoxyl sulfate causes mineralocorticoid receptor activation in chronic kidney disease () - Aug 30, 2020 - Abstract #JSN2020JSN_553; [Methods] 9-week-old CKD model rats (5/6 nephrectomy) were prepared and divided into sham group, CKD group, and CKD+AST-120 administration group, and blood, urine, and renal tissues at 13-week-old were evaluated...Activation of MR transcription and elevation of MR protein levels were significantly suppressed by co-treatment with α-lipoic acid, an antioxidant. [Conclusion] Part of MR activation in CKD is mediated by IS, suggesting the involvement of oxidative stress as a mechanism.
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A Study on the Optimal Treatment Intervention Timing of AST-120 in CKD () - Aug 30, 2020 - Abstract #JSN2020JSN_28; [Conclusion] This study showed that administration of AST-120 could slow down the decrease of eGFR. Furthermore, it was considered to be useful to administer the drug from a stage with relatively low renal function (eGFR≧40).
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Preclinical, Journal: In vitro activity of AST-120 that suppresses indole signaling in Escherichia coli, which attenuates drug tolerance and virulence. (Pubmed Central) - Jul 22, 2020 However, fosfomycin, in addition to rifampicin, colistin and amikacin were not adsorbed, thus AST-120 can be used together with these drugs for therapy to treat infections. These results suggest another benefit of AST-120, i.e., that it assists antibacterial chemotherapy.
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AST-120 Can Delay the Decline of Renal Function in Patients with CKD (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1250; Background AST-120 (KREMEZIN®, Kureha Chemical, Tokyo, Japan) consists of oral spherical carbonaceous adsorbent, which was approved for use in delaying the initiation of dialysis and ameliorating the symptoms of uremia in patients with progressive chronic kidney disease (CKD)...AST120 is useful for management of CKD patients. Funding Government Support - Non-U.S.
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Oral Adsorbent AST-120 Improves Microcirculatory Impairment in Patients with CKD (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1249; Although FMD did not change during study period, SPP values in lower limbs constantly elevated, and was significantly improved at 12 months after AST-120 administration compared to baseline values (69.7 ± 14.6 vs. 78.8 ± 18.9 mmHg, p<0.05). Conclusion IS-lowering therapy significantly improved micro-circulatory impairment in non-diabetic pre-dialysis CKD patients.
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Glycogen Hepatopathy: An Unusual Cause of Liver Enzymes Elevation in Diabetic Patients (Exhibit Halls 3 and 4 (Street Level)) - Aug 8, 2019 - Abstract #ACG2019ACG_1229; Liver enzymes were, ALP-201 U/L, AST-120 U/L, ALT-125 U/L, GGT 98 U/L)...One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. Future progress is required in understanding the biochemical defects underlying GH and an ideal diagnostic test instead of biopsy to avoid the extensive workup in evaluating suspected cases of GH.
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Review, Journal: Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins. (Pubmed Central) - Apr 26, 2019 Clinical trials that have examined interventions to trap toxic products or reverse gut microbial dysbiosis via oral activated charcoal AST-120, prebiotics and probiotics have not shown impact on cardiovascular or survival outcomes but were limited by sample size and short trials. In summary, the gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD.
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Clinical, Journal: Review of the efficacy of AST-120 (KREMEZIN) on renal function in chronic kidney disease patients. (Pubmed Central) - Apr 7, 2019 In addition, AST-120 may prolong the time to the initiation of dialysis, especially in patients with progressive CKD. For further verification of the clinical efficacy of AST-120, future study inclusion criteria should be determined carefully, defining progressive CKD using markers such as declines in eGFR and sCr elevation.
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Trial completion: A Multicenter, Randomized, Open-labeled, Cross-over, Active-controlled, Phase IV Clinical Trial to Evaluate the Preference of Formulation and the Efficacy and Safety of Renamezin and Kremezin in Pre-dialysis Patients With Chronic Renal Failure (clinicaltrials.gov) - Jul 6, 2017 P4, N=153, Completed, For further verification of the clinical efficacy of AST-120, future study inclusion criteria should be determined carefully, defining progressive CKD using markers such as declines in eGFR and sCr elevation. Active, not recruiting --> Completed
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Enrollment closed, Trial primary completion date: A Multicenter, Randomized, Open-labeled, Cross-over, Active-controlled, Phase IV Clinical Trial to Evaluate the Preference of Formulation and the Efficacy and Safety of Renamezin and Kremezin in Pre-dialysis Patients With Chronic Renal Failure (clinicaltrials.gov) - Oct 11, 2016 P4, N=153, Active, not recruiting, Active, not recruiting --> Completed Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2016 --> Dec 2016
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