title: Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120.
abstract: Chronic kidney disease (CKD) results in the accumulation of metabolic waste products that are normally cleared by the kidney, known as uremia. Many of these waste products are from bacteria metabolites in the gut. Accumulation of uremic toxins in plasma and tissue, as well as the gut-plasma-tissue metabolic axis are important for understanding pathophysiological mechanisms of comorbidities in CKD. In this study, an untargeted metabolomics approach was used to determine uremic toxin accumulation in plasma, liver, heart and kidney tissue in rats with adenine-induced CKD. Rats with CKD were also given AST-120, a spherical carbon adsorbent, to assess metabolic changes in plasma and tissues with the removal of gut-derived uremic toxins. AST-120 decreased >55% of metabolites that were increased in plasma, liver and heart tissue of rats with CKD. CKD was primarily defined by 8 gut-derived uremic toxins, which were significantly increased in plasma and all tissues. These metabolites were derived from aromatic amino acids and soy protein including: indoxyl sulfate, p-cresyl sulfate, hippuric acid, phenyl sulfate, pyrocatechol sulfate, 4-ethylphenyl sulfate, p-cresol glucuronide and equol 7-glucuronide. Our results highlight the importance of diet and gut-derived metabolites in the accumulation of uremic toxins and define the gut-plasma-tissue metabolic axis in CKD.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Velenosi
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Anzel
authors.initials: A
authors.lastname: Hennop
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Feere
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Alvin
authors.initials: A
authors.lastname: Tieu
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Kucey
authors.affiliation: Department of Chemistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Polydoros
authors.initials: P
authors.lastname: Kyriacou
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Laura E
authors.initials: LE
authors.lastname: McCuaig
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Nevison
authors.affiliation: Department of Chemistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kerr
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.|Lawson Health Research Institute, London, Ontario, Canada.|Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Urquhart
mesh_terms: D000368:Aged; D000818:Animals; D002244:Carbon / Q000008:administration & dosage*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D010087:Oxides / Q000008:administration & dosage*; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010087:Oxides; D002244:Carbon; C040896:AST 120