Abstract
BackgroundAutologous arteriovenous (AV) fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO)-signaling. Chronic kidney disease (CKD) is associated with oxidative stress that can disturb NO-signaling. Here, we evaluated the influence of CKD on AV fistula maturation and NO-signaling.MethodsCKD was established in rats by a 5/6th nephrectomy and after 6 weeks, an AV fistula was created between the carotid artery and jugular vein, which was followed up at 3 weeks with ultrasound and flow assessments. Vessel wall histology was assessed afterwards and vasoreactivity of carotid arteries was studied in a wire myograph. The soluble guanylate cyclase (sGC) activator BAY 60–2770 was administered daily to CKD animals for 3 weeks to enhance fistula maturation.ResultsCKD animals showed lower flow rates, smaller fistula diameters and increased oxidative stress levels in the vessel wall. Endothelium-dependent relaxation was comparable but vasorelaxation after sodium nitroprusside was diminished in CKD vessels, indicating NO resistance of the NO-receptor sGC. This was confirmed by stimulation with BAY 60–2770 resulting in increased vasorelaxation in CKD vessels. Oral administration of BAY 60–2770 to CKD animals induced larger fistula diameters, however; flow was not significantly different from vehicle-treated CKD animals.ConclusionsCKD induces oxidative stress resulting in NO resistance that can hamper AV fistula maturation. sGC activators like BAY 60–2770 could offer therapeutic potential to increase AV fistula maturation.
Highlights
The prevalence of end-stage renal disease (ESRD) has increased during the last decade and amounted over 500.000 patients in the United States in 2009.[1]
Endothelium-dependent relaxation was comparable but vasorelaxation after sodium nitroprusside was diminished in Chronic kidney disease (CKD) vessels, indicating nitric oxide (NO) resistance of the NO-receptor soluble guanylate cyclase (sGC)
CKD induces oxidative stress resulting in NO resistance that can hamper AV fistula maturation. sGC activators like BAY 60–2770 could offer therapeutic potential to increase AV fistula maturation
Summary
The prevalence of end-stage renal disease (ESRD) has increased during the last decade and amounted over 500.000 patients in the United States in 2009.[1]. Non-maturation occurs in 28–53% of the radiocephalic fistulas, with higher incidence in older, female patients and patients with extensive vascular disease.[4, 5] According to the Dialysis Access Consortium, maturation of an AV fistula is defined as the ability to use the fistula for dialysis within 4 months after fistula creation, and a minimum flow of 300mL/min for at least 8 dialysis sessions during the ensuing 30 days.[6]. Increased flow will raise shear stress that stimulates endothelial cells (ECs) to synthesize nitric oxide (NO) that induces vessel dilation via cyclic guanosine monophosphate (cGMP) signaling.[8,9,10] NO binds to its cognate receptor soluble guanylate cyclase (sGC) in the smooth muscle cell (SMC), facilitating the conversion of guanosine triphosphate (GTP) into the second messenger cGMP. Autologous arteriovenous (AV) fistulas are the first choice for vascular access but have a high risk of non-maturation due to insufficient vessel adaptation, a process dependent on nitric oxide (NO)-signaling. We evaluated the influence of CKD on AV fistula maturation and NO-signaling.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
