Thrombosed Arteriovenous Fistula for Hemodialysis Access is Characterized by a Marked Inflammatory Activity

Background: Thrombosis is the dominant cause of failure of arteriovenous fistulas for hemodialysis access. Vascular inflammation, an important pathologic change in various human vascular diseases, may be involved in the thrombotic process of arteriovenous fistulas.

Methods: The inflammatory activities of 23 thrombosed and 13 non-thrombosed stenotic arteriovenous fistulas were compared by investigating the contents of macrophages and lymphocytes, and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) using immunohistochemistry method. The expression of matrix metalloproteinase (MMP)-2 and MMP-9, which play important roles in thrombosis of human coronary artery, was also investigated. The immunoreaction results were characterized using a semiquantitative scoring system.

Results: The macrophage and lymphocyte contents of the thrombosed group were abundant, and markedly greater than those of the non-thrombosed group (P < 0.001 and P = 0.001, respectively). The infiltration of macrophages and neovasculature were spatially closely correlated. The expressions of VCAM-1, IL-6, and TNF-alpha, but not ICAM-1, were significantly higher in the thrombosed group (P = 0.031, P = 0.010, P < 0.001, and P= 1.000, respectively). The expression of MMP-2 was not different in either groups (P = 0. 344). Differential expression of MMP-9 by macrophages near the vascular lumen, but not those distant from the lumen, was observed in most thrombosed specimens.

Conclusion: This study demonstrated that the thrombosed arteriovenous fistula was characterized by marked inflammation. We hypothesize that the preferential expression of MMP-9 at luminal edge may cause disruption of the anticoagulant endothelial barrier and contribute to luminal thrombosis of arteriovenous fistulas.