Inflammation, oxidation and venous neointimal hyperplasia precede vascular injury from AVF creation in CKD patients

• Authors: Haimanot Wasse, Emory University; Rong Huang, Emory University; Nawazish Ali Naqvi, Emory University; Eileen Smith, Emory University; dezhi Wang, University of Alabama at Birmingham; Ahsan Husain, Emory University
• Journal Title: Journal of Vascular Access
• Volume: Volume 13, Number 2
• Publisher: Wichtig Editore | 2012-04, Pages 168-174
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.5301/jva.5000024
• Keywords: AVF; CKD; Dialysis access; Inflammation; Oxidation

Abstract

Purpose Intimal hyperplasia (IH), a well-recognized cause of dialysis vascular access failure, is generally believed to be an acquired pathologic lesion. Recent data suggests that IH is present prior to AVF creation. We sought to determine whether pre-existing inflammation and oxidation co-exist with IH prior to their incorporation into an AVF conduit, as their presence may predispose the AVF to further IH following AVF creation. Methods At the time of first AV access surgery, vein segments were collected from ten Stage 4 and 5 CKD patients undergoing AVF creation 6-12 months prior to anticipated dialysis initiation. Morphometry and immunohistochemistry was performed to detect inflammatory markers IL-6, TGF-β1, and TNFa, and markers of DNA oxidative damage (8-Hydroxy-2′-deoxyguanosine [HNE]) and lipid peroxidation (4-Hydroxy-2-Nonenal [8OHdG]). Results The degree of IH severity was variable. IL-6, TGF-β1, and TNFa co-localized with a-smooth muscle actin prominently within the venous intima and media. Although more diffuse, HNE and 8OHdG were intensely expressed in parallel with the inflammatory markers. In spite of these findings, however, neither extant IH nor the intensity of inflammatory or oxidative markers were associated with primary or secondary AVF failure at 12 month follow-up. Conclusions Not only does venous IH pre-exist, but inflammation and oxidation markers are present within veins used for the AVF conduit prior to its creation in CKD patients as early as one year before dialysis is commenced. Nevertheless, short and long-term AVF outcomes were not associated with the inflammatory or oxidative burden, suggesting the complexity of AVF dysfunction in humans with CKD.