The cardiovascular effect of the uremic solute indole-3 acetic acid.

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.

Dou L ，Sallée M ，Cerini C ，Poitevin S ，Gondouin B ，Jourde-Chiche N ，Fallague K ，Brunet P ，Calaf R ，Dussol B ，Mallet B ，Dignat-George F ，Burtey S ... -  《-》

Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells.

Addi T ，Poitevin S ，McKay N ，El Mecherfi KE ，Kheroua O ，Jourde-Chiche N ，de Macedo A ，Gondouin B ，Cerini C ，Brunet P ，Dignat-George F ，Burtey S ，Dou L ... -  《-》

Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway.

Gondouin B ，Cerini C ，Dou L ，Sallée M ，Duval-Sabatier A ，Pletinck A ，Calaf R ，Lacroix R ，Jourde-Chiche N ，Poitevin S ，Arnaud L ，Vanholder R ，Brunet P ，Dignat-George F ，Burtey S ... -  《-》

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

Bennis Y ，Cluet Y ，Titeca-Beauport D ，El Esper N ，Ureña P ，Bodeau S ，Combe C ，Dussol B ，Fouque D ，Choukroun G ，Liabeuf S ... -  《Toxins》

Aryl Hydrocarbon Receptor and Uremic Toxins from the Gut Microbiota in Chronic Kidney Disease Patients: Is There a Relationship between Them?

Brito JS ，Borges NA ，Anjos JSD ，Nakao LS ，Stockler-Pinto MB ，Paiva BR ，Cardoso-Weide LC ，Cardozo LFMF ，Mafra D ... -  《-》