Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease

Megan Rossi, Katrina L Campbell, David W Johnson, Tony Stanton, David A Vesey, Jeff S Coombes, Kassia S Weston, Carmel M Hawley, Brett C McWhinney, Jacobus P J Ungerer, Nicole Isbel

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Abstract

BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are nephro- and cardiovascular toxins, produced solely by the gut microbiota, which have pro-inflammatory and pro-oxidative properties in vitro. We undertook this study to investigate the associations between IS and PCS and both inflammation and oxidative stress in the chronic kidney disease (CKD) population.

METHODS: In this cross-sectional observational cohort study, participants with stage 3-4 CKD who enrolled in a randomized controlled trial of cardiovascular risk modification underwent baseline measurements of serum total and free IS and PCS (measured by ultraperformance liquid chromotography), inflammatory markers (interferon gamma [IFN-γ], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), antioxidant and oxidative stress markers (plasma glutathione peroxidase [GPx] activity, total antioxidant capacity [TAC] and F2-isoprostanes) and pulse wave velocity (PWV), a marker of arterial stiffness.

RESULTS: There were 149 CKD patients (59% male; age 60 ± 10 years; 44% diabetic) with a mean eGFR of 40 ± 9 mL/min/1.73 m(2) (range 25-59). Serum free and total IS were independently associated with serum IL-6, TNF-α and IFN-γ, whereas serum free and total PCS were independently associated with serum IL-6 and PWV. Free IS and PCS were additionally independently associated with serum GPx but not with TAC or F2-isoprostanes.

CONCLUSIONS: IS and PCS were associated with elevated levels of selected inflammatory markers and an antioxidant in CKD patients. PCS was also associated with increased arterial stiffness. Inflammation and oxidative stress may contribute to the nephro- and cardiovascular toxicities of IS and PCS. Intervention studies targeting production of IS and PCS by dietary manipulation and the subsequent effect on cardiovascular-related outcomes are warranted in the CKD population.

Original languageEnglish
Pages (from-to)309-17
Number of pages9
JournalArchives of Medical Research
Volume45
Issue number4
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Indican
Chronic Renal Insufficiency
Sulfates
Oxidative Stress
Cross-Sectional Studies
Inflammation
Proteins
Antioxidants
Serum
F2-Isoprostanes
Interleukin-6
Pulse Wave Analysis
Vascular Stiffness
Glutathione Peroxidase
Interferon-gamma
Tumor Necrosis Factor-alpha
Interferon-alpha
Population
Observational Studies
Cohort Studies

Cite this

Rossi, Megan ; Campbell, Katrina L ; Johnson, David W ; Stanton, Tony ; Vesey, David A ; Coombes, Jeff S ; Weston, Kassia S ; Hawley, Carmel M ; McWhinney, Brett C ; Ungerer, Jacobus P J ; Isbel, Nicole. / Protein-bound uremic toxins, inflammation and oxidative stress : a cross-sectional study in stage 3-4 chronic kidney disease. In: Archives of Medical Research. 2014 ; Vol. 45, No. 4. pp. 309-17.
@article{7f2361b55bd34864b581e153d16d673d,
title = "Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease",
abstract = "BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are nephro- and cardiovascular toxins, produced solely by the gut microbiota, which have pro-inflammatory and pro-oxidative properties in vitro. We undertook this study to investigate the associations between IS and PCS and both inflammation and oxidative stress in the chronic kidney disease (CKD) population.METHODS: In this cross-sectional observational cohort study, participants with stage 3-4 CKD who enrolled in a randomized controlled trial of cardiovascular risk modification underwent baseline measurements of serum total and free IS and PCS (measured by ultraperformance liquid chromotography), inflammatory markers (interferon gamma [IFN-γ], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), antioxidant and oxidative stress markers (plasma glutathione peroxidase [GPx] activity, total antioxidant capacity [TAC] and F2-isoprostanes) and pulse wave velocity (PWV), a marker of arterial stiffness.RESULTS: There were 149 CKD patients (59{\%} male; age 60 ± 10 years; 44{\%} diabetic) with a mean eGFR of 40 ± 9 mL/min/1.73 m(2) (range 25-59). Serum free and total IS were independently associated with serum IL-6, TNF-α and IFN-γ, whereas serum free and total PCS were independently associated with serum IL-6 and PWV. Free IS and PCS were additionally independently associated with serum GPx but not with TAC or F2-isoprostanes.CONCLUSIONS: IS and PCS were associated with elevated levels of selected inflammatory markers and an antioxidant in CKD patients. PCS was also associated with increased arterial stiffness. Inflammation and oxidative stress may contribute to the nephro- and cardiovascular toxicities of IS and PCS. Intervention studies targeting production of IS and PCS by dietary manipulation and the subsequent effect on cardiovascular-related outcomes are warranted in the CKD population.",
author = "Megan Rossi and Campbell, {Katrina L} and Johnson, {David W} and Tony Stanton and Vesey, {David A} and Coombes, {Jeff S} and Weston, {Kassia S} and Hawley, {Carmel M} and McWhinney, {Brett C} and Ungerer, {Jacobus P J} and Nicole Isbel",
note = "Copyright {\circledC} 2014 IMSS. Published by Elsevier Inc. All rights reserved.",
year = "2014",
doi = "10.1016/j.arcmed.2014.04.002",
language = "English",
volume = "45",
pages = "309--17",
journal = "Archivos de Investigacion Medica",
issn = "0188-4409",
publisher = "Elsevier",
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Rossi, M, Campbell, KL, Johnson, DW, Stanton, T, Vesey, DA, Coombes, JS, Weston, KS, Hawley, CM, McWhinney, BC, Ungerer, JPJ & Isbel, N 2014, 'Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease' Archives of Medical Research, vol. 45, no. 4, pp. 309-17. https://doi.org/10.1016/j.arcmed.2014.04.002

Protein-bound uremic toxins, inflammation and oxidative stress : a cross-sectional study in stage 3-4 chronic kidney disease. / Rossi, Megan; Campbell, Katrina L; Johnson, David W; Stanton, Tony; Vesey, David A; Coombes, Jeff S; Weston, Kassia S; Hawley, Carmel M; McWhinney, Brett C; Ungerer, Jacobus P J; Isbel, Nicole.

In: Archives of Medical Research, Vol. 45, No. 4, 2014, p. 309-17.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Protein-bound uremic toxins, inflammation and oxidative stress

T2 - a cross-sectional study in stage 3-4 chronic kidney disease

AU - Rossi, Megan

AU - Campbell, Katrina L

AU - Johnson, David W

AU - Stanton, Tony

AU - Vesey, David A

AU - Coombes, Jeff S

AU - Weston, Kassia S

AU - Hawley, Carmel M

AU - McWhinney, Brett C

AU - Ungerer, Jacobus P J

AU - Isbel, Nicole

N1 - Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

PY - 2014

Y1 - 2014

N2 - BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are nephro- and cardiovascular toxins, produced solely by the gut microbiota, which have pro-inflammatory and pro-oxidative properties in vitro. We undertook this study to investigate the associations between IS and PCS and both inflammation and oxidative stress in the chronic kidney disease (CKD) population.METHODS: In this cross-sectional observational cohort study, participants with stage 3-4 CKD who enrolled in a randomized controlled trial of cardiovascular risk modification underwent baseline measurements of serum total and free IS and PCS (measured by ultraperformance liquid chromotography), inflammatory markers (interferon gamma [IFN-γ], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), antioxidant and oxidative stress markers (plasma glutathione peroxidase [GPx] activity, total antioxidant capacity [TAC] and F2-isoprostanes) and pulse wave velocity (PWV), a marker of arterial stiffness.RESULTS: There were 149 CKD patients (59% male; age 60 ± 10 years; 44% diabetic) with a mean eGFR of 40 ± 9 mL/min/1.73 m(2) (range 25-59). Serum free and total IS were independently associated with serum IL-6, TNF-α and IFN-γ, whereas serum free and total PCS were independently associated with serum IL-6 and PWV. Free IS and PCS were additionally independently associated with serum GPx but not with TAC or F2-isoprostanes.CONCLUSIONS: IS and PCS were associated with elevated levels of selected inflammatory markers and an antioxidant in CKD patients. PCS was also associated with increased arterial stiffness. Inflammation and oxidative stress may contribute to the nephro- and cardiovascular toxicities of IS and PCS. Intervention studies targeting production of IS and PCS by dietary manipulation and the subsequent effect on cardiovascular-related outcomes are warranted in the CKD population.

AB - BACKGROUND AND AIMS: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are nephro- and cardiovascular toxins, produced solely by the gut microbiota, which have pro-inflammatory and pro-oxidative properties in vitro. We undertook this study to investigate the associations between IS and PCS and both inflammation and oxidative stress in the chronic kidney disease (CKD) population.METHODS: In this cross-sectional observational cohort study, participants with stage 3-4 CKD who enrolled in a randomized controlled trial of cardiovascular risk modification underwent baseline measurements of serum total and free IS and PCS (measured by ultraperformance liquid chromotography), inflammatory markers (interferon gamma [IFN-γ], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), antioxidant and oxidative stress markers (plasma glutathione peroxidase [GPx] activity, total antioxidant capacity [TAC] and F2-isoprostanes) and pulse wave velocity (PWV), a marker of arterial stiffness.RESULTS: There were 149 CKD patients (59% male; age 60 ± 10 years; 44% diabetic) with a mean eGFR of 40 ± 9 mL/min/1.73 m(2) (range 25-59). Serum free and total IS were independently associated with serum IL-6, TNF-α and IFN-γ, whereas serum free and total PCS were independently associated with serum IL-6 and PWV. Free IS and PCS were additionally independently associated with serum GPx but not with TAC or F2-isoprostanes.CONCLUSIONS: IS and PCS were associated with elevated levels of selected inflammatory markers and an antioxidant in CKD patients. PCS was also associated with increased arterial stiffness. Inflammation and oxidative stress may contribute to the nephro- and cardiovascular toxicities of IS and PCS. Intervention studies targeting production of IS and PCS by dietary manipulation and the subsequent effect on cardiovascular-related outcomes are warranted in the CKD population.

U2 - 10.1016/j.arcmed.2014.04.002

DO - 10.1016/j.arcmed.2014.04.002

M3 - Article

VL - 45

SP - 309

EP - 317

JO - Archivos de Investigacion Medica

JF - Archivos de Investigacion Medica

SN - 0188-4409

IS - 4

ER -