Abstract
Elevated circulating uremic toxins are associated with a variety of symptoms and organ dysfunction observed in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are representative uremic toxins that exert various harmful effects. We recently showed that IS induces metabolic alteration in skeletal muscle and causes sarcopenia in mice. However, whether organ-specific accumulation of IS and PCS is associated with tissue dysfunction is still unclear. We investigated the accumulation of IS and PCS using liquid chromatography/tandem mass spectrometry in various tissues from mice with adenine-induced CKD. IS and PCS accumulated in all 15 organs analyzed, including kidney, skeletal muscle, and brain. We also visualized the tissue accumulation of IS and PCS with immunohistochemistry and mass spectrometry imaging techniques. The oral adsorbent AST-120 prevented some tissue accumulation of IS and PCS. In skeletal muscle, reduced accumulation following AST-120 treatment resulted in the amelioration of renal failure-associated muscle atrophy. We conclude that uremic toxins can accumulate in various organs and that AST-120 may be useful in treating or preventing organ dysfunction in CKD, possibly by reducing tissue accumulation of uremic toxins.
Highlights
We demonstrated that the uremic toxins Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) accumulate in systemic organs and the circulation
We recently reported that accumulated IS in skeletal muscle induces metabolic alterations We recently reported that accumulated IS in skeletal muscle induces metabolic alterations by by oxidative stress, leading to uremic sarcopenia in chronic kidney disease (CKD) [17]
The present findings suggest that tissue that tissue accumulation of uremic toxins results in increased Pai1 expression and aryl hydrocarbon receptor (AhR) signaling, accumulation of uremic toxins results in increased Pai1 expression and AhR signaling, implying the implying the induction of inflammatory processes
Summary
Uremic toxins accumulate in the circulation with the progression of chronic kidney disease (CKD).Because the accumulated uremic toxins exert deleterious effects, they increase morbidity in CKD.Beyond affecting the kidney, retention of uremic toxins is involved in the various complications that occur in CKD, including hypertension, cardiovascular diseases, neurological impairment, bone disorders, and muscle wasting syndrome [1,2,3,4,5].Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are well-studied representative uremic toxins with cytotoxic, pro-inflammatory, and pro-fibrotic effects [5,6,7,8,9]. Uremic toxins accumulate in the circulation with the progression of chronic kidney disease (CKD). Because the accumulated uremic toxins exert deleterious effects, they increase morbidity in CKD. Retention of uremic toxins is involved in the various complications that occur in CKD, including hypertension, cardiovascular diseases, neurological impairment, bone disorders, and muscle wasting syndrome [1,2,3,4,5]. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are well-studied representative uremic toxins with cytotoxic, pro-inflammatory, and pro-fibrotic effects [5,6,7,8,9]. IS and PCS induce oxidative stress and pro-inflammatory effects in the kidney. The pro-inflammatory effect of IS occurs at least partly through activation of the aryl hydrocarbon receptor (AhR)/NF-κB pathway.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
