Abstract 194: Increased Monocyte Adhesion and Infiltrative Activity Inhibits Arteriovenous Fistula Maturation for Hemodialysis Access in Patients With End-stage Renal Disease
Introduction Patients with end-stage renal disease (ESRD) require hemodialysis access and arteriovenous fistulas (AVFs) are the preferred method for hemodialysis access. However, 60% of surgically constructed AVFs do not functionally mature and 80% of the reported AVF failures are caused by stenosis at the venous outflow of the fistula. Stenosis is commonly associated with deregulated inflammatory mechanisms and prolonged systemic inflammation is proposed to upregulate monocyte activity within the vessel, affecting vascular remodeling.
Hypothesis We hypothesize that excessive monocyte interaction with the vessel endothelium from systemic inflammation attenuates AVF maturation and prevents appropriate vascular remodeling. The purpose of this study is to compare monocyte activity through adhesion molecule expression, adhesion to endothelium, and transendothelial migration in patients with a matured AVF versus patients with a failed AVF.
Methods Peripheral blood was collected from control subjects (n=4) and ESRD patients with failed (n=4) and matured (n=8) AVFs. Endothelial cell adhesion, transendothelial migration, and permeability assays were assessed under static conditions. Flow cytometry was used to determine the presence of monocyte adhesion molecules CD18, CD11a, CD11b, and CD11c.
Results Monocytes from failed AVF patients exhibited greater expression of CD18 (p= 0.03) and CD11b (p= 0.03) compared to matured AVF patients. Monocytes from failed AVF patients had greater adherence to endothelium in untreated (p= 0.02) conditions compared to matured AVF patients. Monocytes from failed AVF patients had insignificantly greater transendothelial migration towards fMLP (p= 0.2) compared to matured AVF patients. Monocytes from all ESRD patients had more adhesion to endothelium compared to controls (p= 0.01). All ESRD patients had greater transmigration towards fMLP (p= 0.03) compared to controls.
Conclusion In conclusion, monocytes isolated from patients with failed AVFs have greater CD18/CD11 expression, cell adhesion to the vessel endothelium, and endothelial dysfunction than those from matured AVFs.
- © 2013 by American Heart Association, Inc.