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

Rossi M., Campbell K.L., Johnson D.W., Stanton T., Vesey D.A., Coombes J.S., Weston K.S., Hawley C.M., McWhinney B.C., Ungerer J.P.J. and Isbel N. (2013) Protein-bound uremic toxins, inflammation and oxidative stress: A cross-sectional study in stage 3-4 chronic kidney disease. Archives of Medical Research, 45 4: 309-317. doi:10.1016/j.arcmed.2014.04.002


Author Rossi M.
Campbell K.L.
Johnson D.W.
Stanton T.
Vesey D.A.
Coombes J.S.
Weston K.S.
Hawley C.M.
McWhinney B.C.
Ungerer J.P.J.
Isbel N.
Title Protein-bound uremic toxins, inflammation and oxidative stress: A cross-sectional study in stage 3-4 chronic kidney disease
Journal name Archives of Medical Research   Check publisher's open access policy
ISSN 1873-5487
0188-4409
Publication date 2013-11-30
Sub-type Article (original research)
DOI 10.1016/j.arcmed.2014.04.002
Open Access Status Not Open Access
Volume 45
Issue 4
Start page 309
End page 317
Total pages 9
Place of publication Philadelphia, PA, U.S.A.
Publisher Elsevier Inc.
Language eng
Subject 2700 Medicine
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% ma≤ age 60 ± 10 years; 44% diabetic) with a mean eGFR of 40 ± 9 mL/min/1.73 m2 (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.
Keyword Indoxyl sulfate
Inflammation
Oxidative stress
P-cresyl sulfate
Uremic toxins
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Human Movement and Nutrition Sciences Publications
School of Medicine Publications
 
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