NDT Advance Access originally published online on March 22, 2006
Nephrology Dialysis Transplantation 2006 21(9):2432-2438; doi:10.1093/ndt/gfl070
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
Paclitaxel-coated expanded polytetrafluoroethylene haemodialysis grafts inhibit neointimal hyperplasia in porcine model of graft stenosis
1 Clinical Research Center, Samsung Biomedical Research Institute, 2 Department of Chemistry and Molecular Engineering, Seoul National University, 3 Division of Vascular Surgery, 4 Department of Pathology, 5 Division of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine and 6 Mitech Co., Seoul, Korea
Correspondence and offprint requests to: Dae Joong Kim, MD, Division of Nephrology, Samsung Medical Center, 50 Ilwondong, Kangnamgoo, Seoul, Korea 135-710. Email: kimdjsmc{at}dreamwiz.com, kimdjmed{at}hanmail.net
Background. The main pathology of haemodialysis graft stenosis is venous neointimal hyperplasia at graft–venous anastomoses. Neointimal hyperplasia is also observed in cases of coronary artery in-stent restenosis. Paclitaxel is a chemotherapeutic agent used to treat cancer, and has been proven to inhibit neointimal hyperplasia of coronary artery in-stent restenosis. In this study, we examined whether a paclitaxel-coated haemodialysis graft could inhibit neointimal hyperplasia and prevent stenosis.
Methods. We dip-coated paclitaxel on expanded polytetrafluoroethylene (ePTFE) grafts at a dose density of 0.59 µg/mm2. In vitro release tests showed an initial paclitaxel burst followed by a long-term slow release. Using ePTFE grafts with (coated group, n = 8) or without a paclitaxel coating (control group, n = 11), we constructed arteriovenous (AV) grafts connecting the common carotid artery and the external jugular vein in Landrace pigs.
Results. After excluding seven pigs for technical failure, cross-sections of graft–venous anastomoses obtained 6 weeks after placing the AV grafts were analysed. Percentage luminal stenosis, ratios of intima to media in whole cross-sections, areas of intima in the peri-junctional areas (within 2 mm above and 2 mm below the graft–venous junction), and the mean thickness of intima within venous sides of cross-sections, were 60.5% (range, 41.5–60.7), 13.0 (range, 8.6–20.4), 23.7 mm2 (range, 10.8–32.1) and 2.1 mm (range, 1.1–3.0), respectively, in the control group, whereas corresponding median values in the coated group were 10.4% (range, 1.0–17.8), 1.0 (range, 0.7–5.1), 1.6 mm2 (range, 0.2–8.0) and 0.3 mm (range, 0.1–2.2). All parameters were significantly different between the two groups (P<0.05 by Mann–Whitney test).
Conclusion. Paclitaxel-coated ePTFE grafts could prevent neointimal hyperplasia and the stenosis of AV haemodialysis grafts.
Keywords: access; graft; haemodialysis; paclitaxel; polytetrafluoroethylene; stenosis
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