Transforming Growth Factor-β₁ May Be Involved in Shunt Obstruction in Patients on Chronic Hemodialysis

Abstract

Obstructed shunt vessels were studied immunohistochemically to clarify the mechanism of shunt obstruction in hemodialysis patients. The subjects were 12 hemodialysis patients with shunt obstruction, and 8 patients newly started on hemodialysis were used as the controls. Cryosections of shunt tissue were prepared and stained for thrombomodulin as well as transforming growth factor-β₁ using the enzyme antibody method. In the obstructed shunt group, the intima was significantly thicker than in the control group. In addition, staining of the intima for thrombomodulin was decreased in the obstructed shunt group when compared with the controls. Staining for transforming growth factor-β₁ was related to intimal thickening and cell proliferation. These results indicate that release of thrombomodulin occurs with vascular endothelial cell damage and that transforming growth factor-β₁ may be involved in intimal hypertrophic change and shunt obstruction.

Physiologic Inhibitors of Coagulation in Patients on Chronic Hemodialysis

“…Ishii et al [30] reported that thrombomodulin was only increased in patients dialyzed with regenerated cellulose and polymethylmethacrylate membranes, but not in those dialyzed with ethylene vinyl alcohol and polysulfone membranes. As thrombomodulin values correlated with the failure rate of hemodialysis vascular access, it was also taken as a marker for endothelial injury leading to arteriovenous shunt failure, which is in agreement with data from other reports [48,51].…”

“…It must be cautioned, however, that TFPI may only be a surrogate marker of thrombosis, as it cannot be directly involved in thrombin generation due to its blocking effect on the TF pathway. More recently, the same group of researchers reported a possible role for transforming growth factor‐β1 in shunt obstruction, with release of thrombomodulin as a marker of endothelial injury [51].…”

Low Plasma Activated Protein C-Protein C Inhibitor Complex Concentration Is Associated with Vascular Access Failure in Hemodialysis Patients

“…In addition, patients with impaired kidney function have higher than normal levels of P-TM-ag. We were not able to confirm that postdialysis P-TM-ag levels were significantly elevated compared to predialysis levels [10,11,12,13] or that the P-TM-ag values were correlated with failure of the vascular access [14, 15]. Our results regarding P-TM-ag are supported by the fact that we also measured P-TM-act, which was not correlated with the failure of vascular access.…”

“…Significantly elevated predialysis plasma levels of soluble plasma TM fragments (P-TM-ag) have been demonstrated in HD patients relative to healthy controls [5,6,7,8,9,10]. In addition, postdialysis P-TM-ag levels have been shown to be significantly elevated compared to predialysis levels [11,12,13]. Finally, P-TM-ag values have been found to correlate with the failure of vascular access [11, 12].…”

“…In addition, postdialysis P-TM-ag levels have been shown to be significantly elevated compared to predialysis levels [11,12,13]. Finally, P-TM-ag values have been found to correlate with the failure of vascular access [11, 12]. The concentration of the complex between APC and PCI in plasma (P-APC-PCI complex) is an indirect measure of the amount of APC.…”