title: Chronic kidney disease aggravates arteriovenous fistula damage in rats.
abstract: Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.
authors.affiliation: European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, University Hospital RWTH Aachen, Aachen, Germany. slanger@ukaachen.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Langer
authors.forename: Maria
authors.initials: M
authors.lastname: Kokozidou
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kranz
authors.forename: Tina
authors.initials: T
authors.lastname: Kessler
authors.forename: Niklas
authors.initials: N
authors.lastname: Paulus
authors.forename: Thilo
authors.initials: T
authors.lastname: Krüger
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jacobs
authors.forename: Christina
authors.initials: C
authors.lastname: Lente
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Koeppel
mesh_terms: D000225:Adenine / Q000009:adverse effects; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001794:Blood Pressure / Q000502:physiology; D002114:Calcinosis / Q000209:etiology* / Q000503:physiopathology*; D002908:Chronic Disease; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000601:surgery; D005268:Femoral Vein / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000601:surgery; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D014463:Ultrasonography
chemical_list: D000225:Adenine