Intimal Changes in the Cephalic Vein of Renal Failure Patients before Arterio-Venous Fistula (AVF) Construction

Abstract

Native cephalic vein remains the superior dialysis conduit, even thirty years after it was first described. However, up to 37% of hemodialysis patients develop progressive stenosis in the venous circuit of arterio-venous fistula (AVF), which may later cause thrombosis and occlusion. To study the pre-existing morphological changes in the wall of the cephalic vein before AVF construction, we collected 23 cephalic vein specimens from 3 normal, young trauma and twenty renal failure patients. The samples were collected at the time of vascular repair in the first group and AVF construction in the second group. Sections were prepared and stained for both light and transmission electron microscopy (TEM) examination. Compared with normal cephalic vein, all pre-access cephalic veins showed thickening of the wall and intimal hyperplasia. Other changes were loss of internal elastic lamina in 9 (45%) patients, loss of endothelial cell layer in 6 (30%), inflammatory cell infiltration of the wall in 5 (25%), mural calcification in 3 (15%) and telangiectasia in 2 (10%). Other ultrastructural changes observed were intimal hypertrophy, degeneration and loss of the endothelial cells, degeneration and fraying of smooth muscle cells (SMCs) and loss of wall components into the lumen. In conclusion, most of the apparently normal cephalic veins of renal failure patients showed morphological abnormalities at the time of AVF construction, which may well influence the outcome of shunts in terms of future stenosis and failure. It seems likely that the later development of AVF stenosis may be the result of pre-existing disease rather than the direct insult of arterialization.

Structural and Functional Properties of Venous Wall: Relationship between Elastin, Collagen, and Smooth Muscle Components and Viscoelastic Properties

“…According to the findings reported in this study, the viscoelastic differences were associated with structural variations that could be involved in the origin of the intimal hyperplasia and the vascular access dysfunction. Indeed, several works pointed out that veins collected from different territories exhibit functional changes originated at the end stage renal failure [24,25]; these changes are disadvantages additional to the previously existing physiological structural and functional differences described in this study.…”

Novel Paradigms for Dialysis Vascular Access

“…In patients undergoing AVF creation, preexisting radial artery neointimal hyperplasia (16) and increased intima-media thickness in the radial artery correlated with early failure of radiocephalic AVFs (17). In these patients, there is preexisting neointimal hyperplasia on the cephalic vein (12,18) and major changes in the vascular SMC component (19) are present even before AVF construction, making arterial vessel less compliant. Thus, previous conditions of arm blood vessels strongly influence the outcome of vascular access, in early as well as in late AVF failure.…”

Hemodialysis Vascular Access Dysfunction

“…At a histological level early AVF failure is also characterized by aggressive neointimal hyperplasia in both animal and human models, seen as early as 1 month in animals 63,71 and 3 months in humans 64,66 . The underlying factors (upstream events) which may contribute to early AVF failure, include 4,[72][73][74][75][76][77][78][79][80][81] : (1) small diameter sizes in the vein and artery, (2) surgical injury at the time AV fistula placement, (3) previous venipunctures, (4) development of accessory veins after surgery, (5) hemodynamic shear stress at the AV anastomosis, (6) a genetic predisposition to vascular constriction and neointimal hyperplasia, and (7) pre-existing venous neointimal hyperplasia. The subsequent sections will focus on the downstream events and three main mechanisms responsible for neointimal hyperplasia such as oxidative stress, inflammation, endothelial dysfunction, and alternative origins of neointimal-derived cells.…”

“…The presence of uremia in hemodialysis patients has been shown to exacerbate endothelial dysfunction, possibly through the pathways of inflammation and oxidative stress described above 101,102 . In the specific context of vascular access stenosis, endothelial dysfunction is likely to be responsible for the development of pre-existing venous neointimal hyperplasia [77][78][79][80][81] , medial hypertrophy 77,81 and radial artery intima-media thickening [103][104][105] that is present even before the creation of AVFs in uremic patients. Pre-existing arterial intima-media thickness has been correlated with future AVF dysfunction 103 .…”