A snapshot of early venous remodeling in a 7-day-old arteriovenous fistula

Abstract

Early remodeling of the arteriovenous fistula (AVF) determines maturation outcomes. However, the cellular response of the venous wall early after AVF creation remains largely enigmatic because of the lack of venous biopsies obtained shortly after anastomosis. This report presents a detailed immunohistochemistry analysis of a pre-access cephalic vein and the resulting seven-day-old AVF that required ligation due to steal syndrome. We test for markers of mature and progenitor endothelial cells (CD31, CD34, VWF), contractile smooth muscle cells and myofibroblasts (MYH11, SMA), and immune cell populations (CEACAM8, CD3, CD20, CD11b, CD45, CD68, CD163, tryptase). We demonstrated near complete endothelial coverage of the fistula at 7 days, a high degree of wall neovascularization, pronounced loss of myofibroblasts and smooth muscle cells, and significant infiltration of mast cells, neutrophils, monocytes, and macrophages. Of interest, the presence of CD163⁺ macrophages in the AVF suggests a reactive response to increased intramural oxygenation. In conclusion, these images provide for the first time a glimpse of early remodeling in a human AVF by immunohistochemistry. This case demonstrates the possibility to obtain additional precious samples of this early stage through future multicenter collaborative efforts.

Keywords: AV fistula; dialysis access; endothelium; inflammation; smooth muscle cells; vascular remodeling.

Figure 1.

Smooth muscle cells, endothelial cells, and leukocyte infiltration in a 7-day-old arteriovenous fistula (AVF). Immunohistochemistry analysis of myosin heavy chain 11 (MYH11) for contractile smooth muscle cells (SMC), α-smooth muscle actin (SMA) for SMC and myofibroblasts, CD31 for endothelial cells, and CD45 for leukocytes in the ligated AVF. Boxes I and II in panel A are magnified in B and C, respectively. The scale bar is 400 μm in A and 100 μm in B–C.

Figure 2.

Progenitor and mature endothelial cells (ECs) in the AVF. Immunohistochemistry stainings for von Willebrand factor (VWF) and CD34 in the ligated AVF. The main endothelium contains mature VWF⁺ CD34⁻ ECs, while microvessels in the media and adventitia are positive for the progenitor EC marker CD34. Boxes I and II are magnified in B and C, respectively. The scale bar is 400 μm in A and 100 μm in B–C.

Figure 3.

Immune cell infiltration in a 7-day-old arteriovenous fistula (AVF). Identification of infiltrated immune cells in the ligated AVF by immunohistochemistry. Neutrophils are positive for CEACAM8, monocytes for CD11b, mast cells for tryptase, T cells for CD3, and B cells for CD20. CD68 and CD163 are markers of macrophages. Boxes in A and C are magnified in B and D, respectively, except for CD3 and CD20 which only appear in the lower magnification. The scale bar is 100 μm in A and C and 60 μm in B and D, except for 100 μm in CD20.