Inflammation, oxidation and venous neointimal hyperplasia precede vascular injury from AVF creation in CKD patients.
OBJECTIVE
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-ß1, 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-ß1, 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.
Division of Nephrology, Emory University, Atlanta, GA 30322, USA. hwasse@emory.edu
Haimanot
H
Wasse
Rong
R
Huang
Nawazish
N
Naqvi
Eileen
E
Smith
Dezhi
D
Wang
Ahsan
A
Husain
D000368:Aged; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004249:DNA Damage; D005260:Female; D005845:Georgia; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000097:blood / Q000150:complications*; D018836:Inflammation Mediators / Q000097:blood; D007674:Kidney Diseases / Q000628:therapy*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D058426:Neointima; D018384:Oxidative Stress; D010865:Pilot Projects; D011446:Prospective Studies; D006435:Renal Dialysis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D034941:Upper Extremity / Q000098:blood supply*; D057772:Vascular System Injuries / Q000097:blood / Q000209:etiology* / Q000473:pathology; D014680:Veins / Q000293:injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D015415:Biomarkers; D018836:Inflammation Mediators