ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-PO469

Levels of Interleukin 8 and Monocyte Chemoattractant Protein-1 Are Associated with Arteriovenous Fistula Events and Upregulated in the Endothelium by Indoxyl Sulfate and TGF-β Pathway

Session Information

  • Dialysis: Vascular Access
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 803 Dialysis: Vascular Access

Authors

  • Bataille, Stanislas, Institut Phocéen de Néphrologie, Clinique Bouchard, ELSAN, Marseille, France
  • Chermiti, Rania, C2VN, Aix-Marseille Université, INSERM, INRAE, Marseille, France
  • Giaime, Philippe, Institut Phocéen de Néphrologie, Clinique Bouchard, ELSAN, Marseille, France
  • Pedinielli, Nathalie, Institut Phocéen de Néphrologie, Clinique Bouchard, ELSAN, Marseille, France
  • Mc kay, Nathalie, C2VN, Aix-Marseille Université, INSERM, INRAE, Marseille, France
  • Lano, Guillaume, C2VN, Aix-Marseille Université, INSERM, INRAE, Marseille, France
  • Tawfik, Addi, C2VN, Aix-Marseille Université, INSERM, INRAE, Marseille, France
  • Mancini, Julien, APHM, Hop Timone, Public Health Department (BIOSTIC), Marseille, France
  • Burtey, Stephane, C2VN, Aix-Marseille Université, INSERM, INRAE, Marseille, France
  • Dou, Laetitia, C2VN, Aix-Marseille Université, INSERM, INRAE, Marseille, France
Background

Arteriovenous fistula (AVF) failure due to stenosis or acute thrombosis is a major concern in haemodialysis (HD) patients. Intimal hyperplasia responsible for AVF stenosis can be caused by several factors like endothelial dysfunction, uremic toxins, and inflammatory/profibrotic molecules. Studies suggest that endothelium-secreted inflammatory molecules Interleukin 8 (IL8) and Monocyte Chemoattractant Protein-1 (MCP-1) trigger intimal invasion of smooth muscle cells and enhance intimal thickening. We investigated the association of IL8 and MCP-1 serum levels with AVF events in haemodialysis patients and studied the ability of the uremic toxin indoxyl sulfate to upregulate IL8 and MCP-1 expression in endothelial cells.

Methods

We conducted a retrospective observational study in 205 haemodialysis patients with AVF. In vitro, we studied the mRNA expression of IL8 and MCP-1 in endothelial cells incubated with indoxyl sulfate at uremic concentration (200µM).

Results

During the study period of 731 days, 64 patients had an AVF event defined as a composite of the first occurrence of AVF thrombosis or AVF stenosis requiring endovascular treatment. Kaplan-Meier analysis revealed that patients with serum levels of IL8 > 0 pg/ml or MCP-1> 720 pg/ml had significantly more AVF events. Serum levels of IL8 and MCP-1 were positively correlated with the levels of the pro-fibrotic molecule TGFβ1 in HD patients. In addition, serum levels of MCP-1 were positively correlated with indoxyl sulfate. In vitro, indoxyl sulfate upregulated endothelial expression of IL8 and MCP-1 by activating its receptor, aryl hydrocarbon receptor, which in turn activated the non-canonical TGFβ pathway involving TAK1, p38 MAPK, and the transcription factor AP-1. The stimulation of the TGFβ signalling pathway by TGFβ1 amplified indoxyl sulfate-mediated IL8 and MCP-1 expression.

Conclusion

We demonstrated that AVF events are associated with high serum levels of IL8 and MCP-1, which are upregulated in the endothelium by activation of the TGFβ non-canonical pathway by the uremic toxin indoxyl sulfate. Our study could provide therapeutic targets to limit intimal hyperplasia and prevent AVF events in haemodialysis patients.

Funding

  • Private Foundation Support