Preexisting venous calcification prior to dialysis vascular access surgery.
ABSTRACT Vascular calcification is present in arterial vessels used for dialysis vascular access creation prior to surgical creation. Calcification in the veins used to create a new vascular access has not previously been documented. The objective of this study was to describe the prevalence of venous calcification in samples collected at the time of vascular access creation. Sixty-seven vein samples were studied. A von Kossa stain was performed to quantify calcification. A semi-quantitative scoring system from 0 to 4+ was used to quantify the percentage positive area for calcification as a fraction of total area (0: 0; 1+: 1-10%; 2+: 11-25%; 3+: 26-50%; 4+: >50% positive). Twenty-two of 67 (33%) samples showed evidence of venous calcification. Histologic examination showed varying degrees of calcification within each cell layer. Among the subset of patients with calcification, 4/22 (18%), 19/22 (86%), 22/22 (100%), and 7/22 (32%) had calcification present within the endothelium, intima, media, and adventitia, respectively. The mean semi-quantitative scores of the 22 samples with calcification were 0.18 ± 0.08, 1.2 ± 0.14, 1.6 ± 0.13, and 0.36 ± 0.12 for the endothelium, intima, media, and adventitia, respectively. Our results demonstrate that vascular calcification is present within veins used to create new dialysis vascular access, and located predominately within the neointimal and medial layers.
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ABSTRACT: Vascular access dysfunction is the most important cause of morbidity and hospitalization in the hemodialysis population in the United States at a cost of well over one billion dollars per annum. Venous neointimal hyperplasia characterized by stenosis and subsequent thrombosis, is the major cause of polytetrafluoroethylene (PTFE) dialysis graft failure. Despite the magnitude of the problem, there are currently no effective therapies for the prevention or treatment of venous neointimal hyperplasia in PTFE dialysis grafts. We believe that this is partly due to the lack of a validated large animal model of arteriovenous stenosis that could be used to test out novel interventions. Seven-centimeter PTFE loop grafts were placed between the femoral artery and vein of domestic pigs. The grafts were removed at 2, 4, 7, 14 and 28 days after surgery and subjected to a detailed histological and immunohistochemical examination. Significant neointimal hyperplasia and venous stenosis developed by 28 days at the graft-vein anastomosis. There was minimal neointimal hyperplasia at the graft-artery anastomosis. Venous neointimal hyperplasia (VNH) was characterized by (a) the presence of smooth muscle cells/myofibroblasts; (b) angiogenesis within both the neointima and adventitia; and (c) the presence of an active macrophage cell layer lining the PTFE graft material. These results are very similar to the human lesion previously described by us in dialysis patients. We have developed and validated a pig model of venous neointimal hyperplasia that is very similar to the human lesion. We believe that this is an ideal model in which to test out novel interventions for the prevention and treatment of clinical hemodialysis vascular access dysfunction.Kidney International 01/2003; 62(6):2272-80. · 7.92 Impact Factor
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ABSTRACT: Arterial calcification in chronic kidney disease (CKD) is associated with increased cardiovascular risk. The mechanisms responsible for arterial calcification include alterations of mineral metabolism and expression of mineral-regulating proteins. Arterial calcification is similar to bone formation, involving differentiation of vascular smooth muscle cells (VSMCs) into phenotypically distinct osteoblast-like cells. Elevated phosphate and/or calcium trigger a concentration-dependent increase of calcium precipitates in VSMC in vitro. The calcification is initiated by VSMC release of membrane-bound matrix vesicles and formation of apoptotic bodies. The presence of serum prevents these changes, indicating the presence of calcification inhibitors. Arterial calcification occurs in two sites: the tunica intima and tunica media. Intimal calcification is a marker of atherosclerotic disease and is associated with arterial stenotic lesions. Medial calcification influences outcome by promoting arterial stiffening whose principal consequences are left-ventricular hypertrophy and altered coronary perfusion. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in CKD patients. Age, duration of dialysis, smoking and diabetes are risk factors for the development of arterial calcification in end-stage renal disease. Oversuppression of parathyroid hormone and low bone turnover potentiate the development of arterial calcification. Arterial disease in CKD patients is characterized by extensive calcification. Evidence has accumulated pointing to the active and regulated nature of the calcification process. Elevated phosphate and calcium may stimulate sodium-dependent phosphate cotransport involving osteoblast-like changes in cellular gene expression. Arterial calcification is responsible for stiffening of the arteries with increased left-ventricular afterload and abnormal coronary perfusion as the principal clinical consequences.Current Opinion in Nephrology and Hypertension 12/2005; 14(6):525-31. · 3.96 Impact Factor
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ABSTRACT: Hemodialysis vascular access dysfunction currently is a huge clinical problem. Although arteriovenous fistulas (AVFs) are the preferred form of permanent dialysis access, they continue to have significant problems with early AVF failure. Although inadequate dilatation of the venous segment was believed to have a role in early AVF failure, the exact pathogenesis of early AVF failure is unknown despite the magnitude of the clinical problem. Case series. Hemodialysis patients. Stenotic venous segments from 4 patients with early AVF failure were subjected to a detailed histological, morphometric, and immunohistochemical analysis. All 4 patients had significant luminal stenosis, primarily as a result of eccentric neointimal hyperplasia. This was confirmed through morphometric analysis, which documented intima-media area and thickness ratios that were greater than unity. Cellular phenotyping studies showed that the majority of cells within the region of neointimal hyperplasia were myofibroblasts, with smaller numbers of contractile smooth muscle cells. We described only a limited number of specimens. We show for the first time that aggressive neointimal hyperplasia is present in venous segment specimens from patients with early AVF failure. Future therapies to address this problem will need to target this pathogenetic pathway.American Journal of Kidney Diseases 11/2007; 50(5):782-90. · 5.29 Impact Factor