Aortic Arch Calcification Predicts Patency Loss of Arteriovenous Fistula in End-Stage Renal Disease Patients.
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SUBMITTER: Yap YS
PROVIDER: S-EPMC4840307 | biostudies-other | 2016 Apr
REPOSITORIES: biostudies-other
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Project description:Rationale & objectiveThe current clinical guidelines for vascular access do not have specific recommendations for older hemodialysis patients. Our study aimed to determine the association of age with arteriovenous fistula (AVF) placement, maturation, and primary and secondary patency loss among older hemodialysis recipients.Study designRetrospective cohort study.Setting & participantsA US national cohort of incident hemodialysis patients 67 years or older (N = 43,851) assembled from the US Renal Data System.ExposureAge at dialysis initiation.OutcomesAVF placement, maturation, primary patency loss, and abandonment.Analytical approachCause-specific and subdistribution proportional hazards models were used to examine the association of age and AVF outcomes, with kidney transplantation, peritoneal dialysis, and death treated as competing events. Age cutoff was identified by restricted cubic splines. We compared crude and inverse probability-weighted cumulative incidence functions using Gray's test.ResultsAs compared with those aged 67-<77 years, patients 77 years or older had significantly lower probabilities of AVF placement (adjusted cause-specific HR [cHR], 0.96 [95% CI, 0.92-0.99]; adjusted subdistribution HR [sHR], 0.92 [95% CI, 0.89-0.95]; Gray's test P < 0.001) and maturation (adjusted cHR, 0.95 [95% CI, 0.91-0.99]; adjusted sHR, 0.93 [95% CI, 0.90-0.97]; P < 0.001). However, age was not associated with AVF primary (adjusted cHR, 1.05 [95% CI, 1.00-1.11]; adjusted sHR, 1.04 [95% CI, 0.99-1.09]; P = 0.09) or secondary (adjusted cHR, 1.06 [95% CI, 0.94-1.20]; adjusted sHR, 1.05 [95% CI, 0.93-1.18]; P = 0.4) patency loss.LimitationsReliance on administrative claims to ascertain AVF outcomes.ConclusionsThe likelihood of AVF maturation is an important consideration for vascular access planning. Age alone should not be the basis for excluding older dialysis patients from AVF creation because maintenance of fistula patency was not reduced with older age despite a modest reduction in fistula maturation.
| S-EPMC7534584 | biostudies-literature
Project description:Objective- Arteriovenous fistulae (AVF) are the most common access created for hemodialysis; however, many AVF fail to mature and require repeated intervention, suggesting a need to improve AVF maturation. Eph-B4 (ephrin type-B receptor 4) is the embryonic venous determinant that is functional in adult veins and can regulate AVF maturation. Cav-1 (caveolin-1) is the major scaffolding protein of caveolae-a distinct microdomain that serves as a mechanosensor at the endothelial cell membrane. We hypothesized that Cav-1 function is critical for Eph-B4-mediated AVF maturation. Approach and Results- In a mouse aortocaval fistula model, both Cav-1 mRNA and protein were increased in the AVF compared with control veins. Cav-1 KO (knockout) mice showed increased fistula wall thickening ( P=0.0005) and outward remodeling ( P<0.0001), with increased eNOS (endothelial NO synthase) activity compared with WT (wild type) mice. Ephrin-B2/Fc inhibited AVF outward remodeling in WT mice but not in Cav-1 KO mice and was maintained in Cav-1 RC (Cav-1 endothelial reconstituted) mice (WT, P=0.0001; Cav-1 KO, P=0.7552; Cav-1 RC, P=0.0002). Cavtratin-a Cav-1 scaffolding domain peptide-decreased AVF wall thickness in WT mice and in Eph-B4 het mice compared with vehicle alone (WT, P=0.0235; Eph-B4 het, P=0.0431); cavtratin also increased AVF patency (day 42) in WT mice ( P=0.0275). Conclusions- Endothelial Cav-1 mediates Eph-B4-mediated AVF maturation. The Eph-B4-Cav-1 axis regulates adaptive remodeling during venous adaptation to the fistula environment. Manipulation of Cav-1 function may be a translational strategy to enhance AVF patency.
| S-EPMC6436985 | biostudies-literature
Project description:The protective effects of statins against stenosis for permanent hemodialysis access have been repeatedly demonstrated in animal studies, but remain controversial in human studies. This study aims to evaluate the association between statin use and permanent hemodialysis access patency using a nationwide hemodialysis cohort. A total of 9862 pairs of statin users and non-users, matched by age and gender, were selected for investigation from 75404 new hemodialysis patients during 2000-2008. The effect of statins on permanent hemodialysis access patency was evaluated using Cox proportional hazards models. Compared with non-users, statin users had an overall 18% risk reduction in the composite endpoint in which angioplasty and recreation were combined (adjusted hazard ratio?=?0.82 [95%CI, 0.78-0.87]) and 21% in recreation of permanent hemodialysis access (adjusted hazard ratio?=?0.79 [95%CI, 0.69-0.80]). Specifically, the protective effect was found for arteriovenous fistula (adjusted hazard ratio?=?0.78[95% CI, 0.73-0.82] for composite endpoint and 0.74 [95% CI, 0.69-0.80] for vascular recreation), but not for arteriovenous grafts (adjusted hazard ratio?=?1.10 [95% CI, 0.98-1.24] and 0.94 [95% CI, 0.83-1.07]). Statins possess a protective effect for arteriovenous fistula against the recreation of permanent hemodialysis access. The results provide a pharmaco-epidemiologic link between basic research and clinical evidence.
| S-EPMC4763284 | biostudies-literature
Project description:Objective:The arteriovenous fistula (AVF) is the preferred method of dialysis access because of its proven superior long-term outcomes.However, women havelower rates of AVF patency andutilizationthan men.We used a novel mouseAVF model that recapitulates human AVF maturation to determine whether there are differences in AVF patency in female and male mice. Methods:Aortocaval fistulas were created in female and male C57BL/6 mice (9-10 weeks). At days 0, 3, 7, and 21, infrarenal inferior vena cava (IVC) and aortic diameters and flow velocity were monitored by Doppler ultrasound and used to calculate the vessel diameter, blood flow, and shear stress. AVF were harvested, and expression of proteins was examined by proteomic analysis and immunofluorescence and of messenger RNA by quantitative polymerase chain reaction analysis. Results:At baseline, female mice weighed less and had lower IVC velocity and smaller magnitudes of shear stress, but there was no significant difference in IVC diameter and thickness. After AVF creation, both female and male mice had similar IVC dilation and thickening with no significant differences in IVC wall thickness at day 21. However, female mice had diminished AVF patency by day 42 (25.7% vs 64.3%; P = .039). During fistula remodeling, female mice had lower IVC mean velocity and shear stress magnitude and increased spectral broadening (days 0-21). Messenger RNA and protein expression of Krüppel-like factor 2, endothelial nitric oxide synthase, and vascular cell adhesion molecule 1 was similar at baseline in female and male mice but increased in the AVF only in male mice but not in female mice (day 21). Proteomic analysis of female and male mice detected 56 proteins expressed at significantly higher levels in the IVC of female mice and 67 proteins expressed at significantly higher levels in the IVC of male mice (day 7); function-specific analysis showed that the IVC of male mice overexpressed proteins that belong to pathways implicated in the regulation of vascular function, thrombosis, response to flow, and vascular remodeling. Conclusions:AVF in female mice have diminished patency, preceded by lower velocity, reduced magnitudes of shear stress, and less laminar flow during remodeling. There is also sex-specific differential expression of proteins involved in thrombosis, response to laminar flow, inflammation, and proliferation. These findings suggest that hemodynamic changes during fistula maturation may play an important role underlying the diminished rates of AVF utilization in women. Clinical Relevance:Women have lower rates of arteriovenous fistula (AVF) utilization than men. Using a mouse AVF model that recapitulates human AVF maturation, we show that female mice have similar AVF remodeling but diminished patency. AVF remodeling in female mice is associated with reduced shear stress and laminar flow; lack of increased transcription and translation of several anti-inflammatory, antiproliferative, and laminar flow response proteins (endothelial nitric oxide synthase, Krüppel-like factor 2, and vascular cell adhesion molecule 1); and different patterns of expression of pathways that regulate thrombosis and venous remodeling. Identifying downstream targets involved in these mechanisms may improve AVF outcomes in female patients.
| S-EPMC7402599 | biostudies-literature
Project description:Low rates of arteriovenous fistula (AVF) maturation prevent optimal fistula use for hemodialysis; however, the mechanism of venous remodeling in the fistula environment is not well understood. We hypothesized that the embryonic venous determinant Eph-B4 mediates AVF maturation. In human AVF and a mouse aortocaval fistula model, Eph-B4 protein expression increased in the fistula vein; expression of the arterial determinant Ephrin-B2 also increased. Stimulation of Eph-B-mediated signaling with Ephrin-B2/Fc showed improved fistula patency with less wall thickness. Mutagenesis studies showed that tyrosine-774 is critical for Eph-B4 signaling and administration of inactive Eph-B4-Y774F increased fistula wall thickness. Akt1 expression also increased in AVF; Akt1 knockout mice showed reduced fistula diameter and wall thickness. In Akt1 knockout mice, stimulation of Eph-B signaling with Ephrin-B2/Fc showed no effect on remodeling. These results show that AVF maturation is associated with acquisition of dual arteriovenous identity; increased Eph-B activity improves AVF patency. Inhibition of Akt1 function abolishes Eph-B-mediated venous remodeling suggesting that Eph-B4 regulates AVF venous adaptation through an Akt1-mediated mechanism.
| S-EPMC5684317 | biostudies-literature
Project description:IntroductionThe 2019 Kidney Disease Outcome Quality Initiative (K/DOQI) guideline recommended evaluating arteriovenous fistula (AVF) malfunction risks primarily based on clinical monitoring, which can be assisted with the value of vascular access flow (Qa). Nevertheless, Qa thresholds recommended by different guidelines vary, ranging from 300 to 500 ml/min. This study investigated the optimal Qa threshold to predict future functional patency in AVFs with Qa <500 ml/min.MethodsBoth the clinical indicators of access dysfunction and the Qa value were monitored in patients receiving hemodialysis by the radiocephalic AVF. Routine access flow surveillance was performed by the ultrasound dilution method (HD03, Transonic Inc.). The development of clinically significant indicators of access dysfunction, which necessitated percutaneous transluminal angiography (PTA) to maintain functional patency, was analyzed in this cohort.ResultsAmong the enrolled 302 patients, Qa of 52 patients was under 500 ml/min. These 52 patients received 2 Qa measurements during the follow-up period. Of these 52 patients, serial Qa of 17 patients varied trivially and their AVF remained functional. Multivariable logistic regression analysis revealed that a low Qa per ideal body weight (IBW) is an independent predictor of AVF functional loss. Receiver operating characteristic curve analysis of Qa/IBW in predicting future AVF functional loss revealed that the best cutoff value of Qa is 7.1 times the IBW.ConclusionFor radiocephalic AVFs with Qa <500 ml/min, the minimally required Qa to maintain access function is associated with individual IBW. The IBW-based Qa threshold assessment would allow more flexibility in the treatment of patients and reduce unnecessary invasive measures.
| S-EPMC8897684 | biostudies-literature
Project description:Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, but 60% of conventional [vein-to-artery (V-A)] AVF fail to mature, and only 50% remain patent at 1 year. We previously showed improved maturation and patency in a pilot study of the radial artery deviation and reimplantation (RADAR) technique that uses an artery-to-vein (A-V) configuration. Here, we show that RADAR exhibits higher rates of maturation, as well as increased primary and secondary long-term patencies. RADAR is also protective in female patients, where it is associated with decreased reintervention rates and improved secondary patency. RADAR and conventional geometries were compared further in a rat bilateral carotid artery-internal jugular vein fistula model. There was decreased cell proliferation and neointimal hyperplasia in the A-V configuration in male and female animals, but no difference in hypoxia between the A-V and V-A configurations. Similar trends were seen in uremic male rats. The A-V configuration also associated with increased peak systolic velocity and expression of Kruppel-like factor 2 and phosphorylated endothelial nitric oxide synthase, consistent with improved hemodynamics. Computed tomography and ultrasound-informed computational modeling showed different hemodynamics in the A-V and V-A configurations, and improving the hemodynamics in the V-A configuration was protective against neointimal hyperplasia. These findings collectively demonstrate that RADAR is a durable surgical option for patients requiring radial-cephalic AVF for hemodialysis access.
| S-EPMC7705473 | biostudies-literature
Project description:Arteriovenous fistulae (AVF) are the most common access created for hemodialysis, but up to 60% do not sustain dialysis within a year, suggesting a need to improve AVF maturation and patency. In a mouse AVF model, Akt1 regulates fistula wall thickness and diameter. We hypothesized that inhibition of the Akt1-mTORC1 axis alters venous remodeling to improve AVF patency. Daily intraperitoneal injections of rapamycin reduced AVF wall thickness with no change in diameter. Rapamycin decreased smooth muscle cell (SMC) and macrophage proliferation; rapamycin also reduced both M1 and M2 type macrophages. AVF in mice treated with rapamycin had reduced Akt1 and mTORC1 but not mTORC2 phosphorylation. Depletion of macrophages with clodronate-containing liposomes was also associated with reduced AVF wall thickness and both M1- and M2-type macrophages; however, AVF patency was reduced. Rapamycin was associated with improved long-term patency, enhanced early AVF remodeling and sustained reduction of SMC proliferation. These results suggest that rapamycin improves AVF patency by reducing early inflammation and wall thickening while attenuating the Akt1-mTORC1 signaling pathway in SMC and macrophages. Macrophages are associated with AVF wall thickening and M2-type macrophages may play a mechanistic role in AVF maturation. Rapamycin is a potential translational strategy to improve AVF patency.
| S-EPMC6667481 | biostudies-literature
Project description:We sought to confirm and extend the understanding of clinical outcomes following creation of a common distal autogenous access, the radiocephalic arteriovenous fistula (RCAVF).BackgroundInterdisciplinary guidelines recommend distal autogenous arteriovenous fistulae as the preferred hemodialysis (HD) access, yet uncertainty about durability and function present barriers to adoption.MethodsPooled data from the 2014-2019 multicenter randomized-controlled PATENCY-1 and PATENCY-2 trials were analyzed. New RC-AVFs were created in 914 patients, and outcomes were tracked prospectively for 3-years. Cox proportional hazards and Fine-Gray regression models were constructed to explore patient, anatomic, and procedural associations with access patency and use.ResultsMean (SD) age was 57 (13) years; 45% were on dialysis at baseline. Kaplan-Meier estimates of 3-year primary, primary-assisted, and secondary patency were 27.6%, 56.4%, and 66.6%, respectively. Cause-specific 1-year cumulative incidence estimates of unassisted and overall RC-AVF use were 46.8% and 66.9%, respectively. Patients with larger baseline cephalic vein diameters had improved primary (per mm, hazard ratio [HR] 0.89, 95% confidence intervals 0.81-0.99), primary-assisted (HR 0.75, 0.64-0.87), and secondary (HR 0.67, 0.57-0.80) patency; and higher rates of unassisted (subdistribution hazard ratio 1.21, 95% confidence intervals 1.02-1.44) and overall RCAVF use (subdistribution hazard ratio 1.26, 1.11-1.45). Similarly, patients not requiring HD at the time of RCAVF creation had better primary, primary-assisted, and secondary patency. Successful RCAVF use occurred at increased rates when accesses were created using regional anesthesia and at higher volume centers.ConclusionsThese insights can inform patient counseling and guide shared decision-making regarding HD access options when developing an individualized end-stage kidney disease life-plan.
| S-EPMC9508986 | biostudies-literature
Project description:BackgroundVery limited therapeutic strategies exist to prevent the primary failure of arteriovenous (AV) fistulas in patients with diabetes.ObjectivesTo investigate whether rosuvastatin could improve the primary patency of AV fistulas in diabetic patients with stage 5 chronic kidney disease (CKD).MethodsThis was a double-blind randomized clinical trial. From July 2012 to September 2018, patients aged between 18 and 65 years with type 2 diabetes and stage 5 CKD were randomized to receive placebo or rosuvastatin (5 mg/day) for 7 days prior to the creation of an AV fistula on the forearm until the 21st day after surgery. Patients were followed up for 180 days after the operation. The primary composite endpoint was the development of fistula immaturity or stenosis. The secondary endpoints were changes in inflammatory markers, oxidative stress, and occurrence of postoperative complications.ResultsA total of 60 patients were enrolled in the study. Rosuvastatin resulted in a 20% reduction in total cholesterol from postoperative day 0 to 28 (p = .0006). The overall rate of AV fistula failure (immaturity or stenosis) was 30%, with no significant difference between patients receiving rosuvastatin and those receiving the placebo (33.3% vs. 26.7%, p = .5731). Although not statistically significant, the administration of rosuvastatin might have increased the incidence of postoperative complications (2.99 vs. 2.39 event rate per 1000 patient-days; odds ratio, 1.33; p = .5986).ConclusionsRosuvastatin showed no significant beneficial effects on the primary patency of AV fistulas in diabetic patients with stage 5 CKD, but might have been associated with the risk of drug-related complications.
| S-EPMC7814325 | biostudies-literature