谷口 良輔

<jats:p> D-dimer is a recognized tool for screening venous thromboembolism, with the standardized cutoff value for the possibility of acute deep vein thrombosis (DVT) being 1 μg/mL. For patients above the threshold, noninvasive ultrasonography examination is recommended. However, considering that carcinomatous status potentially increases D-dimer levels and shortage of ultrasonography technologists in Japan, the cutoff value should be optimized for patients with carcinomas. In total, 1124 consecutive cases from 2017 to 2021 in our division were evaluated. In the carcinoma group (n = 225), no significant association was found between the carcinoma stage (0–3 vs 4) and D-dimer levels ( <jats:italic toggle="yes">P = </jats:italic> .54); therefore, staging was not considered in determining the optimal cutoff value. The median D-dimer level differed by 3.1 μg/mL between carcinomatous and non-carcinomatous states in cases without acute DVT in lower limbs. Thus, we tested the cutoff value of increasing D-dimer concentrations, and a cutoff value of 5 μg/mL demonstrated a high specificity of 42.9%. In screening for acute DVT in lower limbs for carcinoma cases, the D-dimer cutoff value may be increased from 1 to 5 μg/mL. </jats:p>

<h4>Background</h4>Arteriovenous fistulae (AVFs) are the preferred vascular access for hemodialysis in patients with end-stage kidney disease. Chronic kidney disease (CKD) is associated with endothelial injury, impaired AVF maturation, and reduced patency, as well as utilization. Because CKD is characterized by multiple pathophysiological processes that induce endothelial-to-mesenchymal transition (EndMT), we hypothesized that CKD promotes EndMT during venous remodeling and that disruption of endothelial TGF (transforming growth factor)-β signaling inhibits EndMT to prevent AVF failure even in the end-stage kidney disease environment.<h4>Methods</h4>The mouse 5/6 nephrectomy and aortocaval fistula models were used. CKD was created via 5/6 nephrectomy, with controls of no (0/6) or partial (3/6) nephrectomy in C57BL/6J mice. AVFs were created in mice with knockdown of TGF-βR1/R2 (TGF-β receptors type 1/2) in either smooth muscle cells or endothelial cells. AVF diameters and patency were measured and confirmed by serial ultrasound examination. AVF, both murine and human, were examined using Western blot, histology, and immunofluorescence. Human and mouse endothelial cells were used for in vitro experiments.<h4>Results</h4>CKD accelerates TGF-β activation and promotes EndMT that is associated with increased AVF wall thickness and reduced patency in mice. Inhibition of TGF-β signaling in both endothelial cells and smooth muscle cells decreased smooth muscle cell proliferation in the AVF wall, attenuated EndMT, and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. Human AVF also showed increased TGF-β signaling and EndMT.<h4>Conclusions</h4>CKD promotes EndMT and reduces AVF patency. Inhibition of TGF-β signaling, especially disruption of endothelial cell-specific TGF-β signaling, attenuates EndMT and improves AVF patency in mouse AVF. Inhibition of EndMT may be a therapeutic approach of translational significance to improve AVF patency in human patients with CKD.