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Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease
Rossi, Megan Campbell, Katrina Johnson, David Stanton, Tony Vesey, David Coombes, Jeff S. Weston, Kassia S. Hawley, Carmel McWhinney, Brett Ungerer, Jacobus
Rossi, Megan
Campbell, Katrina
Johnson, David
Stanton, Tony
Vesey, David
Coombes, Jeff S.
Weston, Kassia S.
Hawley, Carmel
McWhinney, Brett
Ungerer, Jacobus
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 proinflammatory 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 3e4 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-g], interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-a]), 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 m2 (range 25e59). Serum free and total IS were independently associated with serum IL-6, TNF-a and IFN-g, 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.
Keywords
Date
2014
Type
Journal article
Journal
Archives of Medical Research
Book
Volume
45
Issue
4
Page Range
309-317
Article Number
ACU Department
School of Education
Faculty of Education and Arts
Faculty of Education and Arts
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Event URL
Open Access Status
License
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Controlled