Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study

M Rossi, K Campbell, D Johnson, T Stanton, E Pascoe, C Hawley, G Dimeski, B McWhinney, J Ungerer, N Isbel

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Abstract

BACKGROUND AND AIMS: 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.

METHODS AND 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).

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1035-42
Number of pages8
JournalNutrition, Metabolism and Cardiovascular Diseases
Volume24
Issue number9
DOIs
Publication statusPublished - Sep 2014
Externally publishedYes

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Indican
Chronic Renal Insufficiency
Sulfates
Observational Studies
Cardiovascular Diseases
Chronic Kidney Failure
Serum
Carotid Intima-Media Thickness
Vascular Stiffness
Brachial Artery
Nitroglycerin
Dilatation
Cross-Sectional Studies
History
Kidney

Cite this

Rossi, M ; Campbell, K ; Johnson, D ; Stanton, T ; Pascoe, E ; Hawley, C ; Dimeski, G ; McWhinney, B ; Ungerer, J ; Isbel, N. / Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum : an observational study. In: Nutrition, Metabolism and Cardiovascular Diseases. 2014 ; Vol. 24, No. 9. pp. 1035-42.
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title = "Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study",
abstract = "BACKGROUND AND AIMS: 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.METHODS AND 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).CONCLUSION: 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.",
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Rossi, M, Campbell, K, Johnson, D, Stanton, T, Pascoe, E, Hawley, C, Dimeski, G, McWhinney, B, Ungerer, J & Isbel, N 2014, 'Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study' Nutrition, Metabolism and Cardiovascular Diseases, vol. 24, no. 9, pp. 1035-42. https://doi.org/10.1016/j.numecd.2014.04.006

Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum : an observational study. / Rossi, M; Campbell, K; Johnson, D; Stanton, T; Pascoe, E; Hawley, C; Dimeski, G; McWhinney, B; Ungerer, J; Isbel, N.

In: Nutrition, Metabolism and Cardiovascular Diseases, Vol. 24, No. 9, 09.2014, p. 1035-42.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum

T2 - an observational study

AU - Rossi, M

AU - Campbell, K

AU - Johnson, D

AU - Stanton, T

AU - Pascoe, E

AU - Hawley, C

AU - Dimeski, G

AU - McWhinney, B

AU - Ungerer, J

AU - Isbel, N

N1 - Copyright © 2014 Elsevier B.V. All rights reserved.

PY - 2014/9

Y1 - 2014/9

N2 - BACKGROUND AND AIMS: 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.METHODS AND 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).CONCLUSION: 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.

AB - BACKGROUND AND AIMS: 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.METHODS AND 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).CONCLUSION: 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.

U2 - 10.1016/j.numecd.2014.04.006

DO - 10.1016/j.numecd.2014.04.006

M3 - Article

VL - 24

SP - 1035

EP - 1042

JO - Nutrition, Metabolism and Cardiovascular Diseases

JF - Nutrition, Metabolism and Cardiovascular Diseases

SN - 0939-4753

IS - 9

ER -