title: Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study.
abstract: OBJECTIVE
  There is a growing body of evidence supporting the nephrovascular toxicity of indoxyl sulphate (IS) and p-cresyl sulphate (PCS). Nonetheless, a comprehensive description of how these toxins accumulate over the course of chronic kidney disease (CKD) is lacking.
  
  
  RESULTS
  This cross-sectional observational study included a convenience sample of 327 participants with kidney function categorised as normal, non-dialysis CKD and end-stage kidney disease (ESKD). Participants underwent measurements of serum total and free IS and PCS and assessment of cardiovascular history and structure (carotid intima-media thickness [cIMT, a measure of arterial stiffness]), and endothelial function (brachial artery reactivity [flow-mediated dilation (BAR-FMD); glyceryl trinitrate (BAR-GTN)]). Across the CKD spectrum there was a significant increase in both total and free IS and PCS and their free fractions, with the highest levels observed in the ESKD population. Within each CKD stage, concentrations of PCS, total and free, were significantly greater than IS (all p < 0.01). Both IS and PCS, free and total, were correlated with BAR-GTN (ranging from r = -0.33 to -0.44) and cIMT (r = 0.19 to 0.21), even after adjusting for traditional risk factors (all p < 0.01). Further, all toxins were independently associated with the presence of cardiovascular disease (all p < 0.02).
  
  
  CONCLUSIONS
  More advanced stages of CKD are associated with progressive increases in total and free serum IS and PCS, as well as increases in their free fractions. Total and free serum IS and PCS were independently associated with structural and functional markers of cardiovascular disease. Studies of therapeutic interventions targeting these uraemic toxins are warranted.
authors.affiliation: School of Medicine, University of Queensland, Australia; Translational Research Institute, Brisbane, Queensland, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia. Electronic address: megan_rossi@msn.com.
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.affiliation: School of Medicine, University of Queensland, Australia; Translational Research Institute, Brisbane, Queensland, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Campbell
authors.affiliation: School of Medicine, University of Queensland, Australia; Translational Research Institute, Brisbane, Queensland, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Johnson
authors.affiliation: School of Medicine, University of Queensland, Australia; Department of Cardiology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Stanton
authors.affiliation: School of Medicine, University of Queensland, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Pascoe
authors.affiliation: School of Medicine, University of Queensland, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Hawley
authors.affiliation: School of Medicine, University of Queensland, Australia; Department of Chemical Pathology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Dimeski
authors.affiliation: Department of Chemical Pathology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: B
authors.initials: B
authors.lastname: McWhinney
authors.affiliation: Department of Chemical Pathology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Ungerer
authors.affiliation: School of Medicine, University of Queensland, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: N
authors.initials: N
authors.lastname: Isbel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery; D002318:Cardiovascular Diseases / Q000097:blood*; D059168:Carotid Intima-Media Thickness; D003408:Cresols / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007200:Indican / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D013463:Sulfuric Acid Esters / Q000097:blood*; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; D007200:Indican
keywords: Cardiovascular disease; Chronic kidney disease; Indoxyl sulphate; Uraemic toxins; p-Cresyl sulphate