Arteriovenous Fistula Maturation Research Articles

Arteriovenous Fistula Placement, Maturation, and Patency Loss in Older Patients Initiating Hemodialysis

The 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. Retrospective cohort study. A US national cohort of incident hemodialysis patients 67 years or older (N= 43,851) assembled from the US Renal Data System. Age at dialysis initiation. AVF placement, maturation, primary patency loss, and abandonment. Cause-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. As 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) andmaturation (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. Reliance on administrative claims to ascertain AVF outcomes. The 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.

Authors' Reply

In our paper[1][1] “Early predictors of arteriovenous fistula maturation: A novel perspective on an enduring problem,” we demonstrated a linear relationship between the preoperative arterial diameter and arteriovenous fistula (AVF) maturation. Our finding is novel given that, in much of the

Endovascular Management of The Failure of Maturation of Native Arterio-Venous Fistula due to Outflow Stenosis for Hemodialysis

Abstract Background: Arteriovenous fistula (AVF) is a significant procedure for patient in need of hemodialysis. Failure of maturation due to stenosis is a challenge that needs further intervention. Endovascular treatment allows salvaging these fistulae. Aim of the work: To identify the anatomical causes of maturation failure and to assess immediate and long-term clinical effects of PTA of non-mature native (AVF) caused by outflow stenosis using currently available endovascular techniques. Materials and Methods: This study was performed on forty patient complaining of stenosis of primary AVF. The mean age is 60.5. Patient were followed-up every two weeks for the first 2 months, then every month for 6 months post-intervention clinically and radiologically. Collected data includes patient's demographics, cause of renal failure, characters of primary AVF, variables of endovascular intervention, primary patency, and recurrence of stenosis. Results: AVF type was either brachiocephalic (57.5%), brachiobasilic (32.5%) or radiocephalic (10.0%). Fistulography revealed peripheral venous stenosis in 18 patient (45.0%), central venous stenosis in 14 patient (35.0%) , and juxta-anastomotic stenosis in 8 patient (20%). Our technical success was achieved in 87.5% of cases; the patency rate was 91.0% in a month , 86.0% in 3 months , and 80.0% in 6 months. Complications were reported in 10 cases. The recurrence was reported in 7 patient (17.5% of cases). Conclusion: Endovascular salvage of failing A-V fistulas with PTA and Stenting is safe and effective. It is associated with high success rates, low complication rates, and rendering the immediate reuse of the failing shunt.

A prospective study of arteriovenous fistula failure in a tertiary teaching hospital of Andhra Pradesh, India

Background: An arteriovenous (AV) fistula is an abnormal connection between an artery and a vein. Normally, blood flows from your arteries to your capillaries to your veins. Nutrients and oxygen in your blood travel from your capillaries to tissues in your body. With an arteriovenous fistula, blood flows directly from an artery into a vein, bypassing some capillaries. When this happens, tissues below the bypassed capillaries receive diminished blood supply. Arteriovenous fistula (AVF) is the preferred access for hemodialysis in patients with chronic kidney disease. This study aimed to report the outcomes and common complications of AVF. Methodology: A prospective, study was conducted on 120 patients on hemodialysis in the Department of Surgery GEMS Srikakulam from February-November 2017. The failure rates, complications, and outcomes were assessed in this study. Results: A total of 120 AVF fistulae were created. It was radiocephalic in 94 cases and brachial fistula in 26 cases all of which were constructed in an end-side fashion. AVF maturation was seen in n=105 (87.5%) with the majority occurring in the first 6 weeks with a failure rate of 12.5 % (n=15) who were excluded from the further follow-up. Conclusion: Complications developed in 27.5% (n=33) of patients who were managed appropriately.

Arteriovenous fistula maturation and the influence of fluid dynamics.

Arteriovenous fistula creation is the preferred vascular access for haemodialysis therapy, but has a large failure rate in the maturation period. This period generally lasts 6 to 8 weeks after surgical creation, in which the vein and artery undergo extensive vascular remodelling. In this review, we outline proposed mechanisms for both arteriovenous fistula maturation and arteriovenous fistula failure. Clinical, animal and computational studies have not yet shown a definitive link between any metric and disease development, although a number of theories based on wall shear stress metrics have been suggested. Recent work allowing patient-based longitudinal studies may hold the key to understanding arteriovenous fistula maturation processes.

Creating percutaneous radiocephalic arteriovenous fistulas at the wrist.

Background:The first arteriovenous fistulas were created at the wrist more than 60 years ago. Basic surgical construction techniques remain unchanged with mobilization and repositioning of the vessels followed by a sutured anastomosis. We used the Ellipsys device to construct percutaneous radiocephalic–arteriovenous fistulas at the wrist and report the results.Methods:Data were reviewed retrospectively for all patients who had a percutaneous radiocephalic–arteriovenous fistula created during a 6-month period. Each individual underwent ultrasound vessel mapping in addition to physical examination. When a radiocephalic–arteriovenous fistula was feasible and a communicating vein ⩾ 2 mm in diameter was noted in the distal forearm along with a radial artery ⩾ 2 mm, a percutaneous radiocephalic–arteriovenous fistula was considered and reviewed with the patient.Results:Four individuals met the criteria to consider a percutaneous radiocephalic–arteriovenous fistula and all elected to have the procedure performed. Ages were 54–85 years. Three were diabetic and one was female. All percutaneous radiocephalic–arteriovenous fistulas were technically successful. Two individuals had not yet started dialysis therapy. Successful and repetitive cannulation for the two individuals with catheters was initiated at 4 and 8 weeks post procedure. The two pre-dialysis patients had physiologic arteriovenous fistula maturation (6 mm vein diameter and >500 mL/min flow) at 4 and 12 weeks. There were no procedural or late complications and none required intervention. Follow-up was 8–23 months (mean 16 months).Conclusion:The success of these percutaneous radiocephalic–arteriovenous fistulas suggests that use of the Ellipsys device will be applicable at the wrist in selected patients where appropriate vessel sizes and configurations are found.

Radial artery diameterand and age related functional maturation of the radio-cephalic arteriovenous fistula

BackgroundPrevious studies have not described the relationship between reducing radial artery diameter as well as increasing age and functional maturation of the radio-cephalic arteriovenous fistula (RCAVF) and no data identify these as linear relationship. The objective of this study was to perform trend analysis to assess these aspects.MethodsOur retrospective cohort study enrolled and analyzed 353 follow-up cases that underwent first AVF creation. The artery and vein sizes were measured by ultrasound. We performed follow-up, a minimum of 3 months after surgery. Multivariable logistic regression analysis was used to identify independent risk factors inmaturation. Participant age was categorized into four groups (age ≤ 29, 30–49, 50–69, and 70–90 years). Radial artery diameter was categorized into four groups (≤ 1.9, >1.9 and ≤ 2.1, >2.1 and ≤ 2.4, >2.4 mm) according to median and interquartile ranges. We adjusted for confounders in four logistic models, and primary analyses were based on building ordered category models and tested P values for trends to estimate the relationship of radial artery diameter and each 20-year increase in age with risk of maturation.ResultsThe mature RCAVF group included 301 cases, and the immature group included 52 cases. Radial artery diameter, age, and diabetes were independent risk factors of maturation. Odds ratios (ORs) associated with maturation reduced with increasing age, while ORs increased with increasing radial artery diameter. P values for trends(<0.05) were observed in all four models. A reduction in radial artery diameter and higher age were significantly associated with a higher incidence of immaturity after adjusting the multivariate models. The risks of immaturation were increased by more than 1.54 fold for each 20-year increase and increased by more than 1.34 fold for the smaller radial artery diameter group.ConclusionOur findings suggest that a significantly higher immaturity risk of RCAVF was associated with increasing age and a reduction in radial artery diameter. Our study identified a linear exposure-response relationship of age and radial artery diameter with immaturity incident. A careful selection of patients will be helpful in improving AVF functional maturation.

Prognostic factors for radiocephalic arteriovenous fistula maturation in patients with prior placement of a central venous catheter and relationship with inflammation

Aim: A mature and functional arteriovenous fistula (AVF) is considered the best modality for vascular access(VA) for hemodialysis (HD) treatment but the incidence of early failure is high, especially in patients start their HD with a central venous catheter. The aim of this study was to evaluate the prognostic value and association of certain patient characteristics and specific inflammatory markers with early failure of AVF in patients who started their HD therapy with a CVC and a first autogenous radiocephalic AVF (RCAVF) was created after vascular consultation. Material and Methods: A retrospective review of 168 patients with end-stage renal disease who underwent RCAVF creation by the same surgeon by using the same surgical technique and whose primary vascular access for HD treatment was obtained via CVC at the time of access consultation was performed. The patients enrolled into this study were categorized into two groups as Group 1: patients with early failure (n=46) and Group 2: patients with no failure (n=122).Demographic characteristics, medical comorbidities, preoperative doppler ultrasound mapping results, laboratory parameters, postoperative follow-up details of these patients were collected. Primary patency of all patients, early failure rate, maturation failure rate, duration of CVC was calculated. Results: Female gender was found to be a significant risk factor in early failure of RCAVF (69.5% vs 36.1%; p=0.001). The number of patients whose diameter of cephalic vein&amp;lt; 2 mm were significantly higher in EF group (78.3% vs 22.1 ; p=0.028). The duration of CVC access of group 1 was significantly longer than group 2 (6.8 ± 3.6 months vs 2.3 ± 1.7 months, respectively; p&amp;lt;0.05). Overall maturation failure rate was 12.5% and primary patency at 1 year was 72.6%. Levels of C-Reactive protein (7.2 ± 9.6 vs 3.1 ± 3.3 mg/L, respectively; p=0.001) and neutrophil lymphocyte ratio (2.91± 0.30 vs 2.17 ± 0.22, respectively; p&amp;lt;0.05) was significantly lower at group 2 at one year. Conclusion:In patients whose VA for HD treatment was provided by CVC, small cephalic vein diameter, female gender and systemic inflammation may play a role in early failure of RCAVF.

Laterality of Tunneled Dialysis Catheter Does Not Affect Patency of Subsequent Arteriovenous Access but Has Increased Rates of Reintervention and Swelling

The goal for reliable hemodialysis is establishing permanent vascular access, typically arteriovenous fistulae (AVF) or grafts (AVG) in the upper extremity. However, most patients have a tunneled catheter placed at first to initiate dialysis, usually in an upper extremity central vein. The primary aim of this study is to assess whether the laterality of the dialysis catheter affects the patency of the eventual vascular access. Prior studies have had small sample sizes, been limited to single centers, and looked primarily at AVF maturation and not at patency and important secondary outcomes. The Vascular Quality Initiative data registry was queried retrospectively from August 2011 through May 2019. Subjects were at least 18 years old, required hemodialysis, underwent a vascular access procedure in the upper extremity, and did or did not receive a tunneled catheter in an internal jugular or subclavian vein prior to the vascular access procedure. Subjects with the catheter and AVF/AVG in the same arm were part of the ipsilateral group, and those with the catheter and vascular access in opposite arms were in the contralateral group. We analyzed our data to compare secondary patency between the two groups. Secondary outcomes were rates of upper extremity swelling on the side of the vascular access and reintervention (endovascular or open) for the AVF/AVG. During the study period, 42,921 vascular access procedures were performed with prior tunneled catheter placement: 35,447 (83%) were contralateral, and 7,474 (17%) were ipsilateral. The mean age for all patients was 61.89 ± 14.51 years, and 56.05% (24,057) were male. A Cox regression model showed no association between the loss of secondary patency and laterality group (P = .77). The average time from procedure to occlusion was 308 ± 257.8 days in the contralateral group and 342 ± 312.9 days in the ipsilateral group. In terms of secondary outcomes, a Cox regression model using hazard ratios (HR) showed the ipsilateral group had a 26% higher reintervention rate (HR, 1.26; 95% confidence interval, 1.19-1.34; P < .0001). The ipsilateral group had a 38% higher rate of swelling (HR, 1.38; 95% confidence interval, 1.18-1.62; P < .0001). Both were statistically significant. There is no difference in secondary patency between ipsilateral and contralateral procedures. However, swelling and reintervention rates were higher in the ipsilateral group. The side of the body a dialysis catheter is placed may not affect patency, but one may choose to place the catheter and vascular access on opposite sides to avoid swelling and reintervention.

A Novel Technique to Increase the Maturation Rate of Arteriovenous Fistulae

Given the superior patency of arteriovenous (AV) fistulae and the decreased risk of infection compared with AV grafts, the Kidney Disease Outcomes Quality Initiative guidelines recommend the Fistula First approach. Unfortunately, approximately 18% to 53% of all AV fistulae fail to mature. Our objective is to describe a single-center experience with a novel technique using bovine pericardial patch angioplasty to increase the rate of AV fistula maturation.

Vasoreactivity of the Murine External Jugular Vein and Carotid Artery

Introduction: Impaired venous reactivity has potential to contribute to clinically significant pathologies such as arteriovenous fistula (AVF) maturation failure. Vascular segments commonly used in murine preclinical models of AVF include the carotid artery and external jugular vein. Detailed descriptions of isometric procedures to evaluate function of murine external jugular vein ex vivo have not been previously published. Objective: To establish isometric procedures to measure naive murine external jugular vein reactivity ex vivo. Methods: Vasomotor responses of external jugular veins and ipsilateral common carotid arteries from C57BL/6 mice were evaluated using isometric tension procedures. Results: External jugular veins developed tension (p < 0.05) to potassium chloride and U-46619, but not to phenylephrine, whereas common carotid arteries responded to all 3 agents (p < 0.05). While maximal responses to acetylcholine (ACh) were similar between the venous and arterial segments, the dose required to achieve this value was lower (p < 0.05) in the artery versus vein. Nitric oxide synthase inhibition attenuated (p < 0.05) but did not abolish ACh-evoked vasorelaxation in both vascular segments, whereas cyclooxygenase blockade had no effect. Endothelium-independent vasorelaxation to sodium nitroprusside was similar in the artery and vein. Conclusion: Vasorelaxation and vasocontraction can be reliably assessed in the external jugular vein in C57BL/6 mice using isometric procedures.

P1342OUTCOME OF ELDERLY PATIENTS AFTER PREDIALYSIS VASCULAR ACCESS CREATION

Abstract Background and Aims Guidelines to create vascular access for elderly patients is guided by a number of factors i.e. competing risk of death, high rate of arteriovenous fistula (AVF) maturation failure, and poor vascular access outcomes, influencing the outcomes in this population . Does early creation of AVF in elderly patients with advanced CKD influence dialysis outcomes needs evaluation. Method We conducted a retrospective study among elderly (&amp;gt; 65 years ) who chose to create a permanent vascular access before dialysis initiation were identified between Jan 2014-Jan 2017 in Tertiary care hospital, Lucknow and assessed in 43 elderly patients (aged ≥65 years) with CKD undergoing predialysis AVF . Results They were observed for the frequencies of dialysis initiation, death before dialysis initiation, and dialysis-free survival for 2 years after vascular access creation. 45.6 % were diabetic, 78.9% were hypertensive, and 14.2 % had peripheral vascular disease. In all, 67% of patients with predialysis AVF initiated dialysis within 1 years of access placement, but the overall risk of dialysis initiation was modified by patient age. Only one half of patients initiated dialysis with a functioning AVF, 47.9% of AVFs were created &amp;lt;90 days before dialysis initiation. The primary patency rates were 42.7% at one year and 37.8 % at 2 years. Catheter dependence at dialysis initiation was more common in patients receiving predialysis AVF. In conclusion, most elderly patients with advanced CKD who received predialysis vascular access creation initiated dialysis within 1 year. As a consequence of late predialysis placement or maturation failure, almost one half of patients receiving AVFs initiated dialysis with a catheter. Conclusion Insertion of an AVF closer to dialysis initiation may serve as a “catheter-sparing” approach and allow delay of permanent access placement in selected elderly patients with CKD.

P1335AA NOVEL NON-INVASIVE DOPPLER ULTRASOUND GUIDED MANAGEMENT TECHNIQUE OF ACCESSORY CEPHALIC VEIN AS A CAUSE OF MATURATION FAILURE IN RADIOCEPHALIC DIALYSIS ACCESS

Abstract Background and Aims: Background Arterio-venous fistulae (AVF) are the primary access in considerable number of patients on hemodialysis or approaching hemodialysis. A distally created AVF are preferred over proximal approach, as recommended by the guidelines. Non maturation of AVF fistulae remains a major caveat as compared to arteriovenous grafts. A consensus definition of non-maturation is not well defined; however characteristics of non-maturation include inadequate blood flow. Female gender and forearm location have been identified by previous analysis as predisposing factors for non-maturation. Patients with radiocepalic arterio-venous fistula experience the highest rate of non-maturation rates. One important cause of failed AVF maturation is the presence of collateral or veins or tributaries; this may or may not be associated with stenosis. These tributaries may reduce blood in the primary outflow vein, consequently, leading to delayed maturation of the AVF. Options to overcome this problem include coiling or embolization of the collaterals with variable success rate. Aim To examine the efficacy of a novel non-invasive technique to manage maturation failure in radio- cephalic arteriovenous fistulae, through ultrasound guided compression obliteration of the collaterals (accessory cephalic) as identified cause of maturation failure to augment flow in the primary cephalic vein. Method The application of this maneuver to patients according to selected criteria was approved by the institutional Ethical Review Board. Patients’ selection Non maturation was defined by the Rule of Sixes criteria by endorsed by as follows Flow in the fistula should be greater than 600 mL/min, 6 mm caliber, not more than 6 mm depth, discernible margins and ready for use within six weeks Assessing non-maturation in absence of stenosis Ultrasound and Doppler evaluation of main cephalic and accessory cephalic veins to confirm insufficient flow volume at main cephalic vein used in radio-cephalic AVF due to distributed flow to one or more accessory cephalic veins missed by vascular surgeons during surgical radiocephalic AVF creation. To be eligible for this technique, a downstream stenosis should be ruled out by ultrasound, as in such case angioplasty will offer the ideal treatment. 13 patients with failing to mature AVF were consented to this technique. The consent stated that the techniques is totally non-invasive and that, in case of failure of the technique, an endovascular management by coiling for example or a vascular surgical opinion will be sought without delay. Technique summary: using high frequency probe linear ultrasound to perform long term compression for at least 20 minutes in short axis view over the accessory cephalic vein to obtain complete thrombosis and then examine the main cephalic vein to measure post procedure improving flow volume rate Results Patients’ characteristics 13 patients underwent the procedure. Baseline characteristics are shown below: The technique was successful in 9 (5 males and 4 females) out of 13 patients Not referred to interventional radiologist or vascular surgeons Baseline patient’s characteristics Age(years)Means63±9 SexMale5Female8 Conclusion The novel technique as described may provide a safe non-invasive solution to patient with failing to mature radiocephalic arteriovenous fistula and may be referred for a trial of noninvasive ultrasound guided accessory cephalic vein compression obliteration to avoid invasive interventional radiology techniques or surgical repair. A surgical option remains the ultimate solution in case of failure of this ultrasound guided maneuver.

TGFβ (Transforming Growth Factor-Beta)-Activated Kinase 1 Regulates Arteriovenous Fistula Maturation.

Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access but have high rates of primary maturation failure. Successful AVF maturation requires wall thickening with deposition of ECM (extracellular matrix) including collagen and fibronectin, as well as lumen dilation. TAK1 (TGFβ [transforming growth factor-beta]-activated kinase 1) is a mediator of noncanonical TGFβ signaling and plays crucial roles in regulation of ECM production and deposition; therefore, we hypothesized that TAK1 regulates wall thickening and lumen dilation during AVF maturation. Approach and Results: In both human and mouse AVF, immunoreactivity of TAK1, JNK (c-Jun N-terminal kinase), p38, collagen 1, and fibronectin was significantly increased compared with control veins. Manipulation of TAK1 in vivo altered AVF wall thickening and luminal diameter; reduced TAK1 function was associated with reduced thickness and smaller diameter, whereas activation of TAK1 function was associated with increased thickness and larger diameter. Arterial magnitudes of laminar shear stress (20 dyne/cm2) activated noncanonical TGFβ signaling including TAK1 phosphorylation in mouse endothelial cells. TAK1 is increased in AVF, and TAK1 manipulation in a mouse AVF model regulates AVF thickness and diameter. Targeting noncanonical TGFβ signaling such as TAK1 might be a novel therapeutic approach to improve AVF maturation.

Early Predictors of Arteriovenous Fistula Maturation: A Novel Perspective on an Enduring Problem.

Preoperative ultrasound mapping is routinely used to select vessels meeting minimal threshold diameters for surgical arteriovenous fistula (AVF) creation but fails to improve AVF maturation rates. This suggests a need to reassess the preoperative ultrasound criteria used to optimize AVF maturation. We retrospectively identified 300 catheter-dependent patients on hemodialysis with a new AVF created between 2010 and 2016. We then evaluated the associations of preoperative vascular measurements and hemodynamic factors with unassisted AVF maturation (successful use for dialysis without prior intervention) and overall maturation (successful use with or without prior intervention). Multivariable logistic regression was used to identify preoperative factors associated with unassisted and overall AVF maturation. Unassisted AVF maturation associated with preoperative arterial diameter (adjusted odds ratio [aOR], 1.50 per 1-mm increase; 95% confidence interval [95% CI], 1.23 to 1.83), preoperative systolic BP (aOR, 1.16 per 10-mm Hg increase; 95% CI, 1.05 to 1.28), and left ventricular ejection fraction (aOR, 1.07 per 5% increase; 95% CI, 1.01 to 1.13). Overall AVF maturation associated with preoperative arterial diameter (aOR, 1.36 per 1-mm increase; 95% CI, 1.10 to 1.66) and preoperative systolic BP (aOR, 1.17; 95% CI, 1.06 to 1.30). Using receiver operating curves, the combination of preoperative arterial diameter, systolic BP, and left ventricular ejection fraction was fairly predictive of unassisted maturation (area under the curve, 0.69). Patient age, sex, race, diabetes, vascular disease, obesity, and AVF location were not associated with maturation. Preoperative arterial diameter may be an under-recognized predictor of AVF maturation. Further study evaluating the effect of preoperative arterial diameter and other hemodynamic factors on AVF maturation is needed.

Point-of-care ultrasound for assessing arteriovenous fistula maturity in outpatient hemodialysis.

Point-of-care ultrasound in end-stage renal disease is on the rise. Presently the decision to cannulate an arteriovenous fistula is based on its duration since surgery and physical exam. This study examines the effects of point-of-care ultrasound on decreasing the time to arteriovenous fistula cannulation, time spent with a central venous catheter, and the complications and infections that arise. Prospective point-of-care ultrasound patients were recruited between January 2015 and January 2018, while retrospective data (non-point-of-care ultrasound) were collected via chart review from patients who had fistula creation between November 2011 and May 2014. Patients had point-of-care ultrasound within 3 weeks after arteriovenous fistula creation and were followed for 1 year. Arteriovenous fistula cannulation was initiated when the following parameters were met: diameter > 6 mm (with no depreciable narrowing of more than 20% throughout), depth < 6 mm, and length > 6 cm. Demographic data, as well as time to cannulation and central venous catheter removal, number of infections, complications, and interventions were compared between point-of-care ultrasound and non-point-of-care ultrasound groups using unpaired t-test, chi-square, and Fisher exact test statistical analysis. A total of 37 patients with new arteriovenous fistulas were followed by point-of-care ultrasound compared to 29 non-point-of-care ultrasound patients. Point-of-care ultrasound patients had earlier cannulations (35.5 vs 63.3 days, p < 0.05), shorter central venous catheter duration (68.2 vs 98.3 days, p < 0.05), and less infections (12 vs 19) without differences in complication compared to the non-point-of-care ultrasound. Point-of-care ultrasound facilitates early and safe arteriovenous fistula cannulation leading to a reduction in central venous catheter time and risk of infection. Point-of-care ultrasound may also aid in earlier identification of complications and difficult cannulations.

Pre-operative Patient Specific Flow Predictions to Improve Haemodialysis Arteriovenous Fistula Maturation (Shunt Simulation Study): A Randomised Controlled Trial

An arteriovenous fistula (AVF) needs to mature before it becomes suitable to cannulate for haemodialysis treatment. Maturation importantly depends on the post-operative flow increase. Unfortunately, 20-40% of AVFs fail to mature (FTM). A patient specific computational model that predicts immediate post-operative flow was developed, and it was hypothesised that providing information from this model for planning of fistula creation might reduce FTM rates. A multicentre, randomised controlled trial in nine Dutch hospitals was conducted in which patients with renal failure who were referred for AVF creation, were recruited. Patients were randomly assigned (1:1) to the control or computer simulation group. Both groups underwent a work up, with physical and duplex ultrasonography (DUS) examination. In the simulation group the data from the DUS examination were used for model simulations, and based on the immediate post-operative flow prediction, the ideal AVF configuration was recommended. The primary endpoint was AVF maturation defined as an AVF flow ≥500mL/min and a vein inner diameter of ≥4mm six weeks post-operatively. The secondary endpoint was model performance (i.e. comparisons between measured and predicted flows, and (multivariable) regression analysis for maturation probability with accompanying area under the receiver operator characteristic curve [AUC]). A total of 236 patients were randomly assigned (116 in the control and 120 in the simulation group), of whom 205 (100 and 105 respectively) were analysed for the primary endpoint. There was no difference in FTM rates between the groups (29% and 32% respectively). Immediate post-operative flow prediction had an OR of 1.15 (1.06-1.26; p<.001) per 100mL/min for maturation, and the accompanying AUC was 0.67 (0.59-0.75). Providing pre-operative patient specific flow simulations during surgical planning does not result in improved maturation rates. Further study is needed to improve the predictive power of these simulations in order to render the computational model an adjunct to surgical planning.

Vasoreactivity of the Murine External Jugular Vein and Carotid Artery

Few studies have characterized vasoreactivity of the murine external jugular vein. This segment often is used in preclinical models to evaluate vascular remodeling in response to arteriovenous fistula (AVF) maturation. When an AVF is established, the venous segment is exposed to arterial pressures and disturbed flow patterns that have strong potential to impact vasoreactivity. Before testing this hypothesis in the context of AVF, we sought to establish procedures to comprehensively characterize endothelium‐dependent and vascular smooth muscle function of the carotid artery and external jugular vein from healthy mice. External jugular veins and ipsilateral common carotid arteries were isolated from five‐month‐old male C57BL/6 mice and vasomotor responses were evaluated using isometric tension procedures. External jugular veins developed tension (p&lt;0.05) to the voltage‐gated Ca2+ channel opener potassium chloride (KCl) and the thromboxane A2 receptor agonist U‐46619, but not to the α‐1 receptor agonist phenylephrine (PE), whereas common carotid arteries responded to all three vasocontractile agents in a more robust (p&lt;0.05) manner. While maximal responses (~70%) to the endothelium‐dependent vasodilator acetylcholine (ACh) were similar between the venous and arterial segments, the dose required to achieve this value was lower (p&lt;0.05) in the artery versus the vein. Nitric oxide synthase (NOS) inhibition using L‐NMMA attenuated (p&lt;0.05) but did not abolish ACh‐evoked vasorelaxation in both vascular segments. Endothelium‐independent vasorelaxation to sodium nitroprusside (SNP) was similar in the artery and the vein. Endothelium‐dependent and vascular smooth muscle function can be reliably assessed in the murine external jugular vein of healthy male C57Bl/6 mice. Compared to common carotid arteries, external jugular veins are resistant to PE‐evoked vasocontraction, less responsive to KCl and U‐46619‐evoked vasocontraction, less sensitive to ACh‐evoked vasorelaxation, and equally responsive to NOS inhibition and guanylate cyclase activation via SNP. Ongoing studies will determine if and how external jugular vein function is altered by arterial pressures and disturbed flow patterns that are encountered subsequent to establishing an AVF.Support or Funding InformationJMC (University of Utah Graduate Research Fellowship); YTS (R01DK100505; I01BX004133); JDS (AHA16GRNT31050004, NIH RO3AGO52848, RO1HL141540); TL (R44DK109789, R01HL139692, I01BX003387).

Effect of Natural Vascular Scaffolding Therapy on Rat Arteriovenous Fistula Development

BackgroundA mature arteriovenous fistula (AVF) has sufficient enlargement of vascular lumen (i.e. outward remodeling) and limited neointimal hyperplasia (i.e. inward remodeling) to allow increases in AVF blood flow for dialysis. The required vascular wall distention is likely affected by the integrity of vascular extracellular matrix (ECM). We hypothesized that preserving ECM integrity at the time of AVF creation surgery could improve AVF development. Collagen and elastin are the most abundant vascular ECM components and are key regulators of vascular remodeling. Natural Vascular Scaffolding (NVS) Therapy is known to interlink collagen and elastin by covalently linking these proteins via photoactivation. Thus, we investigated the effect of NVS treatment on AVF development.MethodsFemoral AVFs were created in young Wistar male rats by connecting the femoral artery (side) and femoral vein (end) in the same limb. Immediately after the blood flow was restored and dilatation of the femoral vein occurred, a 10 μl‐drop of the NVS compound (at 2 mg/ml diluted in phosphate buffered saline (PBS)) was placed at the anastomosis perivascularly and incubated for 5 minutes, giving the compound time to diffuse into the vascular wall. Next, the NVS compound was activated by a 1 minute illumination by 450nm light. The control group received a 10 μl‐drop of PBS and the same light activation. The skin was closed immediately after light activation. Rats were euthanized 1 week (early time point, 4 per group) and 4 weeks (later time point, 10 per group) post‐AVF creation for histology and morphometry. Verhoeff‐Van Gieson (VVG)‐stained thin cross‐sections were used to measure the area enclosed by internal elastic lamina (IEL), the area of open lumen, and the area of neointimal hyperplasia (NH) by Image J software. The percent open lumen area was calculated by “open lumen area/IEL‐enclosed area X 100%”. These analyses were done at three locations: the entire AVF, the AVF venous limb, and the AVF arterial limb.ResultsThe animals tolerated the treatment well in both experimental groups. At 1 week, the entire AVF’s lumen looked similar between treated and control groups. At 4 weeks, however, the entire AVF’s open lumen area and % open lumen area were trending larger in treated rats than in control rats, being 2.25 and 1.49‐folds larger, respectively (p=0.062, p=0.052). When the venous and arterial sides of the AVF were considered, the difference in open lumen area occurred in the venous side, where the AVF venous limb’s open lumen area and % open lumen area in treated rats were 4.18 and 1.98‐folds larger than in control rats, respectively (p=0.014, p=0.009). The AVF arterial limb’s open lumen area was similar in both groups. Importantly, the NH area was similar in both groups, regardless of the locations.ConclusionOur studies showed that rats tolerated NVS treatment well and the NVS treatment significantly increased the AVF open lumen area, without significantly affecting the NH area, suggesting that NVS treatment may have therapeutic potential by facilitating outward remodeling to enhance AVF maturation in patients.Support or Funding InformationAlucent Biomedical Inc.

Assessment of ICAM-1 N-glycoforms in mouse and human models of endothelial dysfunction.

Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms. Whether different ICAM-1 N-glycoforms are expressed in vivo during disease is unknown. In this study, using the proximity ligation assay, we assessed the relative formation of high mannose, hybrid and complex α-2,6-sialyated N-glycoforms of ICAM-1 in human and mouse models of atherosclerosis, as well as in arteriovenous fistulas (AVF) of patients on hemodialysis. Our data demonstrates that ICAM-1 harboring HM or hybrid epitopes as well as ICAM-1 bearing α-2,6-sialylated epitopes are present in human and mouse atherosclerotic lesions. Further, HM-ICAM-1 positively associated with increased macrophage burden in lesions as assessed by CD68 staining, whereas α-2,6-sialylated ICAM-1 did not. Finally, both HM and α-2,6-sialylated ICAM-1 N-glycoforms were present in hemodialysis patients who had AVF maturation failure compared to successful AVF maturation. Collectively, these data provide evidence that HM- ICAM-1 N-glycoforms are present in vivo, and at levels similar to complex α-2,6-sialylated ICAM-1 underscoring the need to better understand their roles in modulating vascular inflammation.