Accepted Manuscript Uremic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study M. Rossi, BS K. Campbell, PhD D. Johnson, MBBS PhD PSM T. Stanton, MBBS PhD E. Pascoe, MBiostat C. Hawley, MBBS M Med Sci G. Dimeski, PhD B. McWhinney, MS J. Ungerer, MBBS N. Isbel, MBBS PhD PII:
S0939-4753(14)00138-0
DOI:
10.1016/j.numecd.2014.04.006
Reference:
NUMECD 1282
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 28 January 2014 Revised Date:
12 March 2014
Accepted Date: 8 April 2014
Please cite this article as: Rossi M, Campbell K, Johnson D, Stanton T, Pascoe E, Hawley C, Dimeski G, McWhinney B, Ungerer J, Isbel N, Uremic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study, Nutrition, Metabolism and Cardiovascular Diseases (2014), doi: 10.1016/j.numecd.2014.04.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE PAGE Title: Uremic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study
RI PT
Authors: Rossi M, BS1,3,4 Campbell K, PhD1,4
SC
Johnson D, MBBS PhD PSM1,3,4
Pascoe E, MBiostat1 Hawley C, MBBS M Med Sci1,4 Dimeski G, PhD1,6 McWhinney B, MS 7
Isbel N, MBBS PhD1,4 Affiliations:
TE D
Ungerer J, MBBS7
M AN U
Stanton T, MBBS PhD1,5
Australia
EP
School of Medicine1, and Human Movement Studies2, University of Queensland,
AC C
Translational Research Institute3, Brisbane, Queensland, Australia Department of Nephrology4, Cardiology5 and Chemical Pathology6, Princess Alexandra Hospital, Brisbane, Queensland, Australia Department of Chemical Pathology7, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
1
ACCEPTED MANUSCRIPT
Corresponding author: Megan Rossi, Department if Nephrology, Level 2, ARTS Building, princess Alexandra Hospital,
Fax: 61 731 765 480; Ph: 61 731 765 080 Email: [email protected]
SC
Corresponding author:
RI PT
Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.
Megan Rossi,
AC C
EP
TE D
cresyl sulphate; uremic toxins
M AN U
Key words: Chronic kidney disease; cardiovascular disease; indoxyl sulphate; p-
2
ACCEPTED MANUSCRIPT ABSTRACT Background and aims: There is a growing body of evidence supporting the nephrovascular toxicity of indoxyl sulphate (IS) and p-cresyl sulphate (PCS).
course of chronic kidney disease (CKD) is lacking.
RI PT
Nonetheless, a comprehensive description of how these toxins accumulate over the
Methods and results: This cross-sectional observational study included a convenience sample of 327 participants with kidney function categorised as normal, non-dialysis
SC
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
M AN U
(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
TE D
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 p1g/ 24 hours), overweight (classified as a BMI of 25 or above), poor diabetic control (HbA1c >7%), or hyperlipidemia (defined as low density lipoprotein (LDL)
S0939-4753(14)00138-0
DOI:
10.1016/j.numecd.2014.04.006
Reference:
NUMECD 1282
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 28 January 2014 Revised Date:
12 March 2014
Accepted Date: 8 April 2014
Please cite this article as: Rossi M, Campbell K, Johnson D, Stanton T, Pascoe E, Hawley C, Dimeski G, McWhinney B, Ungerer J, Isbel N, Uremic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study, Nutrition, Metabolism and Cardiovascular Diseases (2014), doi: 10.1016/j.numecd.2014.04.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE PAGE Title: Uremic toxins and cardiovascular disease across the chronic kidney disease spectrum: an observational study
RI PT
Authors: Rossi M, BS1,3,4 Campbell K, PhD1,4
SC
Johnson D, MBBS PhD PSM1,3,4
Pascoe E, MBiostat1 Hawley C, MBBS M Med Sci1,4 Dimeski G, PhD1,6 McWhinney B, MS 7
Isbel N, MBBS PhD1,4 Affiliations:
TE D
Ungerer J, MBBS7
M AN U
Stanton T, MBBS PhD1,5
Australia
EP
School of Medicine1, and Human Movement Studies2, University of Queensland,
AC C
Translational Research Institute3, Brisbane, Queensland, Australia Department of Nephrology4, Cardiology5 and Chemical Pathology6, Princess Alexandra Hospital, Brisbane, Queensland, Australia Department of Chemical Pathology7, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
1
ACCEPTED MANUSCRIPT
Corresponding author: Megan Rossi, Department if Nephrology, Level 2, ARTS Building, princess Alexandra Hospital,
Fax: 61 731 765 480; Ph: 61 731 765 080 Email: [email protected]
SC
Corresponding author:
RI PT
Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia.
Megan Rossi,
AC C
EP
TE D
cresyl sulphate; uremic toxins
M AN U
Key words: Chronic kidney disease; cardiovascular disease; indoxyl sulphate; p-
2
ACCEPTED MANUSCRIPT ABSTRACT Background and aims: There is a growing body of evidence supporting the nephrovascular toxicity of indoxyl sulphate (IS) and p-cresyl sulphate (PCS).
course of chronic kidney disease (CKD) is lacking.
RI PT
Nonetheless, a comprehensive description of how these toxins accumulate over the
Methods and results: This cross-sectional observational study included a convenience sample of 327 participants with kidney function categorised as normal, non-dialysis
SC
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
M AN U
(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
TE D
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 p1g/ 24 hours), overweight (classified as a BMI of 25 or above), poor diabetic control (HbA1c >7%), or hyperlipidemia (defined as low density lipoprotein (LDL)
