Back to Search
Start Over
The cardiovascular effect of the uremic solute indole-3 acetic acid.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2015 Apr; Vol. 26 (4), pp. 876-87. Date of Electronic Publication: 2014 Aug 21. - Publication Year :
- 2015
-
Abstract
- In CKD, uremic solutes may induce endothelial dysfunction, inflammation, and oxidative stress, leading to increased cardiovascular risk. We investigated whether the uremic solute indole-3 acetic acid (IAA) predicts clinical outcomes in patients with CKD and has prooxidant and proinflammatory effects. We studied 120 patients with CKD. During the median study period of 966 days, 29 patients died and 35 experienced a major cardiovascular event. Kaplan-Meier analysis revealed that mortality and cardiovascular events were significantly higher in the higher IAA group (IAA>3.73 µM) than in the lower IAA group (IAA<3.73 µM). Multivariate Cox regression analysis demonstrated that serum IAA was a significant predictor of mortality and cardiovascular events after adjustments for age and sex; cholesterol, systolic BP, and smoking; C-reactive protein, phosphate, body mass index, and albumin; diastolic BP and history of cardiovascular disease; and uremic toxins p-cresyl sulfate and indoxyl sulfate. Notably, IAA level remained predictive of mortality when adjusted for CKD stage. IAA levels were positively correlated with markers of inflammation and oxidative stress: C-reactive protein and malondialdehyde, respectively. In cultured human endothelial cells, IAA activated an inflammatory nongenomic aryl hydrocarbon receptor (AhR)/p38MAPK/NF-κB pathway that induced the proinflammatory enzyme cyclooxygenase-2. Additionally, IAA increased production of endothelial reactive oxygen species. In conclusion, serum IAA may be an independent predictor of mortality and cardiovascular events in patients with CKD. In vitro, IAA induces endothelial inflammation and oxidative stress and activates an inflammatory AhR/p38MAPK/NF-κB pathway.<br /> (Copyright © 2015 by the American Society of Nephrology.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Cardiovascular Diseases etiology
Cyclooxygenase 2 metabolism
Female
Human Umbilical Vein Endothelial Cells
Humans
Male
Middle Aged
Reactive Oxygen Species metabolism
Renal Insufficiency, Chronic complications
Renal Insufficiency, Chronic mortality
Signal Transduction
Uremia complications
Young Adult
Cardiovascular Diseases blood
Endothelium, Vascular metabolism
Indoleacetic Acids blood
Oxidative Stress
Renal Insufficiency, Chronic blood
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 26
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 25145928
- Full Text :
- https://doi.org/10.1681/ASN.2013121283