Arteriovenous Fistula Patency Research Articles

Paclitaxel- or sirolimus-coated balloons used for ArterioVEnous fistulas-2 (PAVE-2): study protocol for a randomised controlled trial to determine the efficacy of paclitaxel- or sirolimus-coated balloons in arteriovenous fistulas used for haemodialysis

BackgroundIn view of the conflicting results from previous studies, the benefit of paclitaxel-coated balloons for arteriovenous fistulas is uncertain and equipoise remains. Although an industry-led trial testing the efficacy of sirolimus-coated balloons in AVFs is in progress, the benefit of sirolimus-coated balloons for arteriovenous fistulas is currently unknown. The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon fistuloplasty to preserve the patency of arteriovenous fistulae used for haemodialysis.MethodsThe study design is a multicentre randomised controlled trial. Following a successful plain balloon fistuloplasty, participants will be randomised to further treatment with a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. We will recruit 642 patients, each with one or two treatment segments, over a 3-year period. Patients will remain in the trial and be followed up for 1 year. The primary endpoint is time to loss of treatment segment primary patency. Cox-proportional hazards models will be used to estimate hazard ratios for the time to loss of treatment segment primary patency for each treatment group relative to the control group. Analysis of the primary endpoint will be based on treatment segments rather than participants and a shared frailty will be estimated to account for the clustering of treatment segments within patients. Secondary endpoints are time to loss of primary patency at any treatment segment; time to end of access circuit primary patency; time to AVF abandonment; number of radiological or surgical interventions; adverse events; intima-media thickness and degree of stenosis at 3 months on ultrasound; and patient quality of life assessed by EQ-5D-5L and VASQoL.DiscussionThe three-armed design in this proposal will provide an answer on the efficacy of both paclitaxel- and sirolimus-coated balloons in the same trial. This trial is likely to provide a clear answer regarding the efficacy of drug-coated balloons for arteriovenous fistulas.Trial registrationISRCTN ISRCTN40182296. Registered on 4 August 2023.

Arterio-Venous Fistula Calcifications—Risk Factors and Clinical Relevance

(1) Background: Arterio-venous fistulas (AVFs) are considered the gold-standard vascular access (VA) in patients on maintenance hemodialysis (HD) therapy. AVF calcifications represent a less studied VA related complication, even though HD patients are at a higher risk for extraosseous calcifications. The aim of this study is to assess the prevalence and risk factors of AVF calcifications, as well as the 5-year impact on AVF functionality and on overall mortality. (2) Methods: We conducted a 5-year prospective study including 161 patients on maintenance HD therapy. At baseline, we collected data related to VA history, comorbidities, demographics, subjective global assessment scale (SGA), and biochemical parameters. All patients underwent a complete AVF ultrasound and we recorded AVF blood flow and the presence of AVF calcifications, stenoses, and aneurysms. (3) Results: In our study, we found an AVF calcification prevalence of 39%. In a univariate analysis, we found that patients with AVF calcifications were associated with other AVF complications as well (stenoses, aneurysms), had longer AVF and HD vintage, as well as higher serum calcium and PTH values. In a multivariate analysis, we found that patients with a longer HD vintage and higher calcium values were independently associated with AVF calcifications. AVF calcifications did not affect 5-year fistula patency, nor were they associated with a higher mortality risk in our group of patients. (4) Conclusions: AVF calcifications were a frequent finding in our analysis, but their presence does not seem to affect the 5-year AVF patency.

Development of a Porcine Model of Arteriovenous Fistula Venous Stenosis Treated with Percutaneous Transluminal Angioplasty

To develop a porcine model for arteriovenous fistula (AVF) venous stenosis treated with percutaneous transluminal angioplasty (PTA) and compare outcomes of plain balloon angioplasty (POBA) to IN.PACT paclitaxel drug-coated balloons (DCB). Twelve castrated male Yorkshire pigs (4-5 months, 35-45kg) underwent renal artery embolization to induce chronic kidney disease (CKD). Twenty-eight days later, AVF was created by anastomosing the left external jugular vein to left common carotid artery. The pigs were divided into a pilot group (n=6) for optimizing the AVF technique (euthanized at day 4) and a definitive group (n=6) for validating PTA outcomes (euthanized at day 42). Stenosis developed at juxta-anastomosis 28 days later and was treated with POBA [pilot group (n=6), definitive group (n=3)] or DCB [definitive group only (n=3)]. Definitive group underwent biweekly 4D Flow MRI scans. All animals developed CKD, with significant increases in BUN (median increase: 2.6 to 3.2 mmol/L, P<0.001) and creatinine (median increase: 100 to 187 μmol/L, P<0.001). In the pilot group, one animal had an infected fistula, and AVF patency was 1/5. In the definitive group, the patency was 5/6 because the AVF technique was modified by resecting the sternomastoid muscle and increasing the spatulation. At day 42 post PTA, DCB treated AVF outflow vein showed increasing blood flow compared to POBA (DCB 209.8 ± 64.42 mm2 vs POBA 170.9 ± 95.52 mm2 p = 0.934). A porcine model of AVF venous stenosis treated with PTA was developed, with blood flow trends favoring DCB over POBA.

Outcomes Following Arteriovenous Fistula Creation in Medicare Beneficiaries With End-Stage Kidney Disease

The objective of this study was to measure the contemporary patency rates and frequency of interventions required for arteriovenous fistula (AVF) care among a representative United States (US) population of end stage kidney disease (ESKD) patients, including by age, race and sex. All Medicare beneficiaries >20 years of age who underwent AVF graft creation for ESKD between 2017 through 2019 were included for analysis. The primary endpoints included primary patency, primary assisted patency, post-intervention patency, and fistula functionality up to one year after AVF placement. Secondary endpoint included admission for an associated adverse event following AVF creation. Multivariate analysis of patency rates was also assessed. Of 43,457 patients included in the analysis, the cumulative primary patency at 90 days was 68.4% and at one year was 31.5%. At one year, the primary assisted patency rate, post-intervention patency, and fistula use were 70.4%, 30.2% and 59.1%, respectively. There was no difference in primary patency rates when comparing age groups (age 40 – 59: HR 1.01 [95% CI 0.95 – 1.06], p = 0.84) or age ≥60: HR 0.99 [95% CI 0.93 – 1.04], p = 0.61) to the reference of age group 20 – 39. Women vs men (HR 1.16 [95% CI 1.14 – 1.20], p < 0.001) and Black vs White patients (HR 1.34 [95% CI 1.31 – 1.38], p < 0.001) and were at higher risk of experiencing primary patency failure. The cumulative incidence of admissions for adverse events was 32.6% at 1-year. In conclusion, our findings suggest that the real-world AVF patency rates remain low, with disproportionately low rates among women and Black patients.

Factors associated with dysfunction of autogenous arteriovenous fistula in patients with secondary hyperparathyroidism after parathyroidectomy

Background Secondary hyperparathyroidism (SHPT) is a prevalent chronic complication in patients undergoing hemodialysis. Parathyroidectomy (PTX) is crucial for reducing mortality and improving the prognosis in the treatment of refractory hyperparathyroidism. However, it is often associated with a number of postoperative complications such as postoperative hypotension, hyperkalemia, and hungry bone syndrome. A previous study demonstrated that low blood pressure influences the patency of autogenous arteriovenous fistulas (AVF). Few studies have examined AVF dysfunction following PTX. This study aimed to identify and describe the risk variables associated with AVF dysfunction after PTX. Methods Cases of AVF dysfunction after PTX between 2015 and 2021 were studied. Four controls were identified for each patient and were matched for sex and age. Biochemical parameters and blood pressure of the patients before and after PTX were recorded. Risk factors for AVF dysfunction after PTX were identified using conditional logistic regression analysis. Results Sixteen patients and 64 controls were included in this study. Baseline demographic and laboratory data were compared. Patients in the AVF dysfunction group had lower levels of postoperative calcium than the controls. After surgery, calcium levels decreased more in patients with AVF dysfunction than in the control group. The decrease in systolic blood pressure (ΔSBP) after PTX was greater in the AVF dysfunction group than that in the control group. For each 1 mmHg increment in ΔSBP, the risk of AVF dysfunction after surgery increased by 11.6% (OR = 1.116, 95% CI, 1.005–1.239, p = .040). The likelihood of developing AVF dysfunction after surgery was twelvefold higher in diabetic patients than in non-diabetic patients (OR = 12.506, 95% CI, 1.113–140.492, p = .041). Among patients with ΔSBP > 5.8 mmHg after PTX, the AVF failure rate was significantly greater in patients with diabetes than in those without diabetes. Patients with a history of AVF failure had a nine-fold higher risk of developing AVF dysfunction (OR = 9.143, 95% CI, 1.151–72.627, p = .036). Serum albumin, hemoglobin, ΔiPTH, and age were not independent predictors of AVF dysfunction. The cutoff value for SBP was 5.8 mmHg, as determined by the Youden index of the receiver operating characteristic curve. Conclusion Decreased systolic blood pressure (ΔSBP) after PTX, diabetes, and AVF failure history were risk factors for AVF dysfunction following PTX in patients with SHPT. Diabetes patients with ΔSBP > 5.8 mmHg were more prone to AVF dysfunction after PTX.

Features associated with arteriovenous fistula patency. A meta-analysis.

It is unclear if cannulation-associated variables such as timing of first cannulation, access creation method, cannulation technique, or needle type are associated with the outcomes of arteriovenous fistulas. We conducted a meta-analysis to investigate such potential associations with 1-year primary patency. Twenty-eight publications with titles that included "arteriovenous fistula," "patency," "cannulation," "metric," "first cannulation," "hemodialysis," "complication," "vascular," "nursing," and "puncture" were retrieved and reviewed. The 1-year primary patency rates ranged from 0.32 to 0.93. Primary patency rates were significantly lower in patients in whom initial cannulation was done less than 1.5 months after fistula creation compared to fistulas first cannulated more than 1.5 months after anastomosis (odds ratio [OR] = 0.41, 95% confidence interval [CI]: 0.32-0.52). The effect of cannulation timing on primary patency rate was attenuated when plastic cannulas were used during the first two to three puncture weeks compared to metal needles (OR = 0.62 vs. 0.34; p = 0.032). Fistulas in the upper arm did not have a higher 1-year primary patency compared to those in the forearm (OR = 1.05, 95% CI: 0.93-1.19). Primary patency of upper arm arteriovenous fistulas was higher in reports from the Americas or Europe compared to reports from Asia. Buttonhole cannulation was not associated with higher patency rates at 1 year compared to rope-ladder cannulation (OR = 1.14, 95% CI: 0.75-1.71). Early cannulation was associated with reduced 1-year arteriovenous fistula patency. This association was reduced when plastic cannulas were used during the initial 2-3 weeks.

Application of prophylactic flow restriction in brachiocephalic arteriovenous fistulas

To investigate the effects of prophylactic flow restriction for brachiocephalic arteriovenous fistula on postoperative high-flow-related complications and patency rate in patients undergoing hemodialysis. Clinical data of patients with end-stage renal disease who underwent brachiocephalic arteriovenous fistula surgery for hemodialysis from February 2017 to May 2022 in Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were retrospectively analyzed. During surgery, a 4-5 mm vascular suture loop was placed around the vein near the anastomosis as a flow restriction device in 43 patients (flow restriction group), while 42 patients did not receive the prophylactic flow restriction ring (control group). All patients were followed up for 1 to 5 years. The incidence rates of complications related to the hemodialysis access pathway, including distal ischemia syndrome, the formation of arteriovenous fistula aneurysms, thrombus, high-flow congestive heart failure, anastomosis of the vein within 1 cm of the anastomosis and cephalic arch stenosis, were compared between the two groups. The natural blood flow rate of the arteriovenous fistula, anastomosis size, the internal diameter of the vein near the anastomosis, primary patency rate, assisted primary patency rate, and secondary patency rate of the arteriovenous fistula, were also evaluated and compared between the two groups. Logistic regression analysis was used to investigate the factors affecting arteriovenous fistula patency rates, as well as the impact of the flow-restricting ring on postoperative factors. Ultrasound measurements showed that the internal diameter of the vein at the site of the flow restriction ring in the flow restriction group was (3.7±0.6) mm at three months postoperatively, which was significantly smaller than the internal diameter of the narrowest part of the vein near the anastomosis in the control group [(4.1±1.0) mm, t=－2.416, P<0.01]. The postoperative anastomotic diameter and natural blood flow rate of the arteriovenous fistula in the flow restriction group were both significantly lower than those in the control group (both P<0.05). Furthermore, the incidence rates of various complications in the flow restriction group were significantly lower than those in the control group (all P<0.05). At 6, 12, and 24 months postoperatively, the primary patency rate and assisted primary patency rate in the flow restriction group were significantly higher than those in the control group (both P<0.05), while there was no significant difference in secondary patency rates between the two groups (P>0.05). Binary logistic regression analysis indicated that age, diabetes, and natural blood flow rate of the arteriovenous fistula at 3 months postoperatively were independent risk factors for primary patency rate, while the flow restriction for brachiocephalic arteriovenous fistula was an independent protective factor for primary patency rate (P<0.01 or P<0.05). The application of flow restriction was negatively correlated with anastomotic diameter at 6 and 12 months, natural arteriovenous fistula blood flow, and the incidence rates of cephalic arch stenosis and aneurysm formation (all P<0.05). The prophylactic constriction during brachiocephalic arteriovenous fistula surgery in patients undergoing hemodialysis can limit the size of the anastomosis and postoperative arteriovenous fistula blood flow, reducing complications such as cephalic arch stenosis and high-flow heart failure, and increasing primary patency rates of arteriovenous fistula and delay the reintervention of the fistula.

Bismuth-infused perivascular wrap facilitates delivery of mesenchymal stem cells and attenuation of neointimal hyperplasia in rat arteriovenous fistulas

BackgroundMesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations. MethodsWe infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in rats with induced chronic kidney disease (n = 3 per time point) for the following groups: control (no wrap), PCL wrap, PCL with MSCs, PCL-Bi (BiNP-infused wrap), and PCL-Bi with MSCs. ResultsPhysicochemical characterization and in vitro biocompatibility tests revealed that BiNP infusion did not alter the wrap's non-cytotoxicity toward vascular cells, hemocompatibility, and capacity for MSC loading but facilitated long-term monitoring via micro-computed tomography. After 8 weeks, all treatment groups demonstrated significant improvement in wall-to-lumen ratio on ultrasonography (P < 0.001), neointima-to-lumen ratio on histomorphometry (P < 0.001), and attenuation of neointimal hypoxia on immunohistochemistry (P < 0.05). Compared to non-MSC wraps, MSC-loaded wraps not only attenuated endothelial dysfunction and neointimal inflammation but also reduced hypoxia and inflammation across all vascular layers. ConclusionThese results demonstrate that MSC delivery through a radiopaque polymeric wrap could enhance AVF patency outcomes through the inhibition of multiple pathways inducing AVF failure.

Endothelial TGF-β Signaling Regulates Endothelial-Mesenchymal Transition During Arteriovenous Fistula Remodeling in Mice With Chronic Kidney Disease.

Arteriovenous fistulae (AVFs) are the preferred vascular access for hemodialysis in patients with end-stage kidney disease. Chronic kidney disease (CKD) is associated with endothelial injury, impaired AVF maturation, and reduced patency, as well as utilization. Because CKD is characterized by multiple pathophysiological processes that induce endothelial-to-mesenchymal transition (EndMT), we hypothesized that CKD promotes EndMT during venous remodeling and that disruption of endothelial TGF (transforming growth factor)-β signaling inhibits EndMT to prevent AVF failure even in the end-stage kidney disease environment. The mouse 5/6 nephrectomy and aortocaval fistula models were used. CKD was created via 5/6 nephrectomy, with controls of no (0/6) or partial (3/6) nephrectomy in C57BL/6J mice. AVFs were created in mice with knockdown of TGF-βR1/R2 (TGF-β receptors type 1/2) in either smooth muscle cells or endothelial cells. AVF diameters and patency were measured and confirmed by serial ultrasound examination. AVF, both murine and human, were examined using Western blot, histology, and immunofluorescence. Human and mouse endothelial cells were used for in vitro experiments. CKD accelerates TGF-β activation and promotes EndMT that is associated with increased AVF wall thickness and reduced patency in mice. Inhibition of TGF-β signaling in both endothelial cells and smooth muscle cells decreased smooth muscle cell proliferation in the AVF wall, attenuated EndMT, and was associated with reduced wall thickness, increased outward remodeling, and improved AVF patency. Human AVF also showed increased TGF-β signaling and EndMT. CKD promotes EndMT and reduces AVF patency. Inhibition of TGF-β signaling, especially disruption of endothelial cell-specific TGF-β signaling, attenuates EndMT and improves AVF patency in mouse AVF. Inhibition of EndMT may be a therapeutic approach of translational significance to improve AVF patency in human patients with CKD.

Establishing an autogenous vascular access program in a Guatemalan comprehensive pediatric nephrology center.

The Guatemalan Foundation for Children with Kidney Diseases collaborated with Bridge of Life, a not-for-profit charitable organization, to establish a vascular access program. We reviewed our experience with graded surgical responsibility and structured didactic training, creating arteriovenous fistulas (AVF) for Guatemalan children. Pediatric vascular access missions were completed from 2015 to 2023 and analyzed retrospectively. Follow-up was completed by the Guatemalan pediatric surgeons, nephrologists, and nursing staff. AVF patency and patient survival were evaluated by Kaplan-Meier life-table analysis with univariate and multivariable association between patient demographic variables by Cox proportional hazards models. Among a total of 153 vascular access operations, there were 139 new patient procedures, forming the study group for this review. The mean age was 13.6years, 42.6% were female, and the mean BMI was 17.3. Radial or ulnar artery-based direct AVFs were established in 100 patients (71.9%) and ten of the 25 transposition procedures. Brachial artery inflow was required in 29 direct AVFs (20.9%). Two patients underwent femoral vein transpositions. Access-related distal ischemia was not encountered. Seven of the AVF patients later required access banding for arm edema; all had previous dialysis catheters (mean = 9, range 4-12). Primary and cumulative patency rates were 84% and 86% at 12months and 64% and 81% at 24months, respectively. The median follow-up was 12months. Overall patient survival was 84% and 67% at 12 and 24months, respectively. There were no deaths related to AVF access. Safe and functional AVFs were established in a teaching environment within a Guatemalan comprehensive pediatric nephrology center.

Inhibition of endothelial to mesenchymal transition in a large animal preclinical arterio-venous fistula model leads to improved remodeling and reduced stenosis.

Vein grafts are used for many indications, including bypass graft surgery and arterio-venous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia and adverse remodeling. Recently, endothelial to mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts. We aimed to evaluate the clinical potential of inhibiting EndMT, and developed the first dedicated preclinical model to study the efficacy of local EndMT inhibition immediately prior to AVF creation. We first undertook pilot studies to optimize the creation of a femoral AVF in pigs and verify that EndMT contributes to neointimal formation. We then developed a method to achieve local in vivo SMAD3 knockdown by dwelling a lentiviral construct containing SMAD3 shRNA in the femoral vein prior to AVF creation. Next, in Phase 1, 6 pigs were randomized to SMAD3 knockdown or control lentivirus to evaluate the effectiveness of SMAD3 knockdown and EndMT inhibition 8 days after AVF creation. In Phase 2, 16 pigs were randomized to SMAD3 knockdown or control lentivirus and were evaluated to assess longer-term effects on AVF diameter, patency and related measures at 30 days after AVF creation.In Phase 1, compared to controls, SMAD3 knockdown achieved a 75% reduction in the proportion of CD31+ endothelial cells co-expressing SMAD3 (p<0.001), and also a significant reduction in the extent of EndMT (p<0.05). In Phase 2, compared to controls, SMAD3 knockdown was associated with an increase in the minimum diameter of the venous limb of the AVF (1.56±1.66 versus 4.26±1.71mm, p<0.01) and a reduced degree of stenosis (p<0.01). Consistent with this, neointimal thickness was reduced in the SMAD3 knockdown group (0.88±0.51 versus 0.45±0.19mm, p<0.05). Furthermore, endothelial integrity (the proportion of luminal cells expressing endothelial markers) was improved in the SMAD3 knockdown group (p<0.05). EndMT inhibition in a preclinical AVF model by local SMAD3 knockdown using gene therapy led to reduced neointimal hyperplasia, increased endothelialization and a reduction in the degree of AVF stenosis. This provides important proof-of-concept to pursue this approach as a clinical strategy to improve the patency of AVFs and other vein grafts.

Reshaping Arteriotomy at the Corners Eases End-to-side Anastomosis: Results and Description of S-shaped Arteriotomy Technique

Background: End to side anastomosis (ESA) poses difficulty at corners in small calibre vessels. S shaped arteriotomy (SSA) overcomes this. Aims: This study presents the results of SSA and explains the concept involved. Settings and Design: It is an observational study with retrospective analysis. Methods and Material: SSA coverts a narrow V at the corners into a broader U which pry open the edges. Altered dynamics acting on arterial wall result in this. SSA was utilised for carrying out arteriovenous fistulas [radio- cephalic and brachio-cephalic arteriovenous fistulas (AVFs)] and crural bypasses. The patency of AVFs was determined by doppler and / or ability to carry out successful dialysis. Crural bypass were followed by doppler and/ or CT angiography for patency. Statistical Analysis Used: Results are presented as a descriptive analysis. Results: One hundred ESAs were done. This included sixty- five radio cephalic AVFs, twenty brachio-cephalic AVFs and fifteen femoro-crural bypasses. The mean diameter of the radial artery was 1.97 +/- 0.24mm; while the average diameter of brachial artery was 3.3 +/- 0.43mm; and that of crural arteries was 2.4 +/- 0.43mm. Twelve radio cephalic AVFs thrombosed, but rest of AVFs matured with a mean follow up of 6 months. The total follow up for crural bypasses was 21 months. The cumulative patency rate was 100 percent at 10 months and 82% at 21 months. Conclusions: SSA helps in better visualising of the corners and facilitates ESA with satisfactory results. This happens due to redistribution of forces acting on the arterial wall.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Improves the Vascular Function of Arteriovenous Fistula in Rats with Hyperglycemia.

Few evidence-based medications to improve the primary patency of arteriovenous fistulas in patients with diabetes who require hemodialysis are available. We investigated whether proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) could improve arteriovenous fistula function through pleiotropic effects in a rat model of hyperglycemia. Ex vivo effects of PCSK9i on the aorta of Sprague-Dawley (SD) rats were investigated using an organ bath system. For in vivo experiments, an abdominal aortocaval (AC) fistula was generated in SD rats (200-250 g) after inducing hyperglycemia through streptozotocin administration (80 mg/kg, intraperitoneal). Alirocumab (50 mg/kg/week, subcutaneous) was administered on the day of fistula surgery and day 7. Echocardiography, blood flow through the aorta-limb, vasomotor reactivity, and serum biochemistry were examined on D14. Furthermore, enzyme-linked immunosorbent assay and immunoblotting were performed. PCSK9i induced aorta relaxation ex vivo through a potassium channel-associated mechanism. PCSK9i significantly improved blood flow and preserved endothelial function without changes in cardiac function and serum lipid levels in rats with hyperglycemia. The levels of lectin-like oxidized low-density lipoprotein receptor-1, superoxide dismutase, cyclooxygenase-2, caspase-1, and interleukin-1β were significantly reduced in the treatment group. PCSK9i decreased the ratio of phosphorylated to total p38 mitogen-activated protein kinase and extracellular signal-regulated kinase in the aorta of rats with hyperglycemia. Short-term treatment with PCSK9i preserved endothelial function, induced vascular dilatation, and increased blood flow in the AC fistula of rats with hyperglycemia. The pleiotropic mechanisms were associated with the suppression of oxidative stress and tissue inflammation during hyperglycemia.

Application of modified no-touch technique in rabbit arteriovenous fistula model and its effect on venous neointimal hyperplasia.

To investigate the technical advantages of a modified no-touch technique (MNTT) in constructing arteriovenous fistulas (AVF) compared to the conventional technique (CT) and assess its potential to reduce neointimal hyperplasia in the outflow vein. Forty-seven New Zealand rabbits were randomly divided into three groups: control, CT, and MNTT. Rabbits in control group were observed using ultrasound and then euthanized to obtain external jugular vein (EJV) for Hematoxylin-eosin (H-E). We established common carotid artery (CCA)-EJV AVF using MNTT in the MNTT group and the CT in the CT group. AVF patency and complications were compared between the CT and MNTT groups. Rabbits with patent AVF in both groups were observed using ultrasound 2 weeks after surgery to evaluate changes in the vessel diameter and blood flow spectrum of the AVFs. H-E staining measured the intima thickness of EJV adjacent to the anastomosis and histologic characteristics of the AVF at 2 and 4 weeks after surgery. Five rabbits died after surgery with common symptoms of sneezing, coughing, runny nose, anorexia, and diarrhea; two in the MNTT group and three in the CT group. There were significant differences in the diameter (p = 0.010) and peak systolic velocities (PSV) (p = 0.001) of EJV between the CT and MNTT groups 2 weeks after surgery. Spiral laminar flow (SLF) was observed in CCA and EJV adjacent to anastomosis in the MNTT group. Additionally, histological observations showed less venous neointimal hyperplasia in the MNTT group than in the CT group 4 weeks after surgery. The rabbit model of CCA-EJV AVF established using MNTT demonstrated fewer complications, larger vein diameters, and reduced venous neointimal hyperplasia, indicating that this maybe an ideal animal model to further investigate the application of MNTT in AVF surgery.

#2778 The Charlson Index can be used prospectively to identify patients who will need a close follow up of surveillance for the vascular access

Abstract Background and Aims The primary screening methods for monitoring vascular access in haemodialysis involve measuring access blood flow and dialysis venous pressure. However, challenges are present in both aspects, potentially hindering the attainment of desired results. Research in this field is crucial to identify the optimal combination of intensive clinical monitoring and supplementary surveillance for effective outcomes. For this reason, we aim to describe the impact of comorbidities and patency of native arteriovenous fistulae (nAVF). Method Descriptive study of prevalent patients on haemodialysis, carried out by consulting electronic medical records over a period of 35 months. Demographic and vascular access-related variables were included. Primary and secondary patency was calculated for all accesses. Patients with upper limb AVF were classified according to distal and proximal access location; and the Charlson Index was used to categorise patients according to comorbidities. Kaplan Meyer survival curves were used to contrast the impact of comorbidities on the different patency. Results 52 patients, age 70.7 ± 1.57 years, 69.2% male, 42.3% diabetic, Charlson index with a median of 7 (6.5 - 7.73), 98.1% with a native fistula, the most frequent nAVF location in our population was humerocephalic (63.5%) and a predominance of the left upper extremity (65.4%). According to the location of the access, adjusted by the Charlson index, it is evident that in proximal accesses (humerocephalic and basilic humerus nAVF), with a Charlson Index less than or equal to 7, the time required to reach an event was statistically significantly longer (Log Rank Test (Mantel-Cox): primary patency p=0.057 and secondary patency p=0.069). This comparison was not significant in distal fistulas. Conclusion Using the Charlson comorbidity index information, we transformed it into an accessible and valuable tool for maintaining vascular access patency. Close follow-up in patients with proximal nAVF and high Charlson comorbidity index could be beneficial.

#2833 Charlson comorbidity index predicts early failure and overall survival of vascular access among diabetic dialysis patients.

Abstract Background and Aims Vascular access (VA) survival is a determinant factor in the morbidity and mortality of haemodialysis patients, directly influencing their quality of life. Some studies have described the influence of diabetes on the reduced survival of arteriovenous fistulas as an independent factor; however, the correlation between other comorbidities in diabetic patients with vascular access survival has been less well documented. Therefore, our aim is to describe the relationship between comorbidities in diabetic haemodialysis patients and arteriovenous fistula (AVF) patency. Method Descriptive, observational and retrospective study in prevalent patients included in a haemodialysis programme by consulting electronic records over a period of 35 months. Demographic variables; related to vascular access and primary and secondary patency of all accesses were included. The Charlson Comorbidity Index was used to categorise diabetic patients according to comorbidities. Kaplan Meyer survival curves were used to contrast the impact of comorbidities on the different patency. Results 22 patients, mean age 68.36 ± 10.9 years, 68.18% male, 31.82% female, Charlson index with a median of 6.5 (5 - 8), 95.45% had a native fistula, with humero-cephalic location being more frequent (72.72%) and predominance of the left upper arm (68.18%). The time required to reach an event in both primary patency and secondary patency in diabetic patients was longer in patients with a Charlson index less than or equal to 7, this being statistically significant (Log Rank Test (Mantel-Cox): primary patency p=0.022 and secondary patency p=0.032). Conclusion The Charlson Comorbidity Index in our population is a significant factor in arteriovenous fistula survival.

#2709 Genome wide association study regarding disturbed AVF patency

Abstract Background and Aims Veins are frequently exposed to arterial circulation, as coronary artery bypass grafts (CABG) and as a peripheral venous bypass to treat atherosclerotic disease, or in the case of arterio-venous fistulas (AVF) to provide a vascular access for hemodialysis. Therapeutic success is dependent on proficient venous remodeling after introduction in the arterial circulation to sustain the increased hemodynamic pressure. Frequently observed adverse outcomes after the aforementioned procedures include the stenosis or total occlusion of the vein, requiring surgical or interventional treatment or leading to bypass/ AVF failure. Hereditary factors associated with disturbed venous patency have been previously investigated in all three conditions. For example, distinct VEGF-A as well as TGF-beta polymorphisms have been identified to correlate with AVF failure. In the present analysis we aimed at investigating whether genetic polymorphisms associated with disturbed venous patency after AVF creation are similar to findings in CABG and peripheral bypass patients in a genome wide association study. Method The analyses were conducted in White Europeans (N= 425,406) in the UK Biobank using regenie software. This software employs a linear mixed model that accounts for the impact of population structure and individual relatedness. Out of approximately 805,000 variants, we selected 606,201 high-quality variants to construct a relatedness model for regenie. These selected variants were identified by a genotyping rate exceeding 80%, minor allele frequencies greater than 1%, and Hardy-Weinberg equilibrium p-values below 10^-8. We adjusted for age, sex, BMI, smoking, and history venous thromboembolism. We assessed the association of 9,757,417 imputed SNPs, each having a minimum allele count of 12 and a minimum info score of 0.3. Results In total, 768 patients underwent at least 1 surgery for AVF creation. Out of those, 341 (44.4%) had a recorded procedure or diagnosis associated with disturbed fistula patency. The controls included 6067 CABGs and 384 peripheral bypasses with 76 (1.3%) and 67 (17.4%) recorded events, respectively. We found no genome wide significant associations for the tested SNPs and patency-related AVF complications (Fig. 1). Additionally, we also found no genome wide significant associations after combining the phenotypes (Fig. 2). Conclusion Multiple studies have evaluated genetic associations and adverse clinical outcomes after AVF creation. Nevertheless, the generalizability of these findings might be limited at least partially due to small sample sizes. While the sample size of the present analysis is similar to previous research efforts and therefore also comparably low, the lack of consistency in results might be suggestive of the difficulties research in this field faces. Additionally, we found no indication that impaired venous patency after AVF creation is related to complications after coronary or peripheral bypass surgery regarding genetic patient profiles. However, whether this is due to differences in pathophysiology and related genetic predispositions or due to the limited sample size and incidence rates of the present study remains to be determined in follow-up investigations.

The influence of near-infrared therapy on arteriovenous fistula patency in haemodialysis patients: A multicentre, randomised, controlled clinical trial.

Arteriovenous fistula (AVF) is the preferred vascular access for patients undergoing haemodialysis (HD). AVF malfunction remains a major clinical problem and is a significant independent risk factor for death. Although far-infrared (FIR) therapy has been shown to reduce complications and improve the patency rate of AVFs in various studies, it has been cautiously recommended by the Kidney Disease Outcome Quality Initiative (KDOQI) guidelines for AVF care due to insufficient evidence. Therefore, it is necessary to identify more effective methods for preventing AVF dysfunction. Many in vitro studies and few clinical studies have examined the effects of near-infrared (NIR) therapy on the vasculature. This study will examine the effects of NIR therapy on AVF. A randomised, controlled, open-label, multicentre trial will compare the effect of NIR on AVF patency after 1 year of therapy with that of a control group of patients with existing AVF. One group of patients received NIR treatment above their AVFs, whereas the control group received regular care. The primary outcome is the primary fistula patency rate within 12 months. In addition, acute changes in inflammatory, vasodilatory and haemodynamic parameters after a single treatment in the first 40 participants will be examined. This study was registered in the Clinical Trials Registry (ChiCTR2300071305) at https://register.clinicaltrials.gov/. This study will explore the long-term and acute effects of NIR on AVFs. The study findings will provide information that can be used to develop new technical support for the prevention of AVF dysfunction in patients undergoing haemodialysis.

Nutritional Strategies to Mitigate Complications and Improve Long-Term Functionality of Autologous Arteriovenous Fistula Post Ultrasound and DSA Guided Balloon Dilation

This prospective cohort study evaluated the efficacy of omega-3 fatty acid supplementation on arteriovenous fistula patency and systemic inflammation in 220 hemodialysis patients undergoing ultrasound and digital subtraction angiography-guided balloon dilation. The participants were randomized into an intervention group receiving 2,000 mg of omega-3 fatty acids daily and a placebo group. The primary outcome measures were arteriovenous fistula patency at 12- and 24-months post-dilation, while secondary outcomes included thrombosis incidence, changes in inflammatory markers (c-reactive protein and interleukin-6), lipid profiles, and health-related quality of life (HRQoL). Results indicated a significant improvement in arteriovenous fistula patency in the omega-3 group at 24 months (80.9 vs. 68.2%, P &lt; 0.05). Additionally, there was a significant reduction in thrombosis rates (7.3 vs. 16.4%, P &lt; 0.05) and inflammatory markers (c-reactive protein and interleukin-6) in the omega-3 group compared to the placebo. Lipid profile analysis showed a decrease in total cholesterol and low-density lipoprotein levels with omega-3 supplementation, with significant changes at 12 months (P &lt; 0.05). HRQoL scores also improved significantly in the omega-3 group at both 12 and 24 months (P &lt; 0.05). These findings suggest that omega-3 fatty acids can enhance arteriovenous fistula functionality and reduce cardiovascular risk factors in hemodialysis patients. And its integration into standard care protocols for patients with arteriovenous fistulas would improve long-term outcomes.

Heat therapy preconditioning improves the skeletal muscle contractile and mitochondrial function in a mouse model of access-related hand dysfunction

Introduction: Hemodialysis via arteriovenous fistula (AVF) is a life-line treatment for patients with end-stage kidney disease. However, hemodialysis access-related hand dysfunction (ARHD) including ischemia, muscle weakness and alterations in mitochondrial function is prevalent following AVF placement. We tested the hypothesis that two-weeks of daily heat therapy prior to AVF surgery would improve hindlimb function in a mouse model of ARHD. Methods: Adult male C57BL/6J mice (N=9-11/group) were fed a 0.2% adenine diet to induce chronic kidney disease. Following two weeks of the initial adenine diet, animals were randomly allocated to heat therapy (HT) or control (CON) groups. Animals assigned to HT were exposed to environmental heat at 40°C in a climate chamber for 30 min/day, six days/week, for two weeks while the control mice were exposed to room temperature (~22°C). The AVF was created using the left common iliac artery and vein 24-48 hours after the last treatment session. Laser Doppler perfusion to the ventral paw was assessed post-operatively (POD) and AVF patency was verified using a high-frequency duplex ultrasound system three days prior to euthanasia. Following 14 days of recovery, in situ tibialis anterior (TA) muscle contractility and gastrocnemius muscle mitochondrial function were assessed. RNA sequencing analysis of the hindlimb skeletal muscle (N=4/group) was performed. Results: Compared to baseline, the level of blood urea nitrogen was similarly elevated ( P&lt;0.05) in both groups following four weeks of adenine diet. In both groups, blood perfusion to the paw was decreased by ~50% immediately after AVF creation and progressively recovered to ~80% at POD13 without a treatment effect ( P=0.4467). No differences in body weight and muscle mass in the TA, extensor digitorum longus, and soleus muscles were observed (all P&gt;0.05). Notably, however, the absolute ( P=0.0250) and specific force ( P=0.0101) frequency relationship of the TA muscle were significantly improved in the animals exposed to HT. In addition, compared with control animals, HT mice had significant improvement in oxidative phosphorylation (OXPHOS) in both pyruvate ( P=0.0145) and octanoylcarnitine ( P=0.0196) fueled conditions. RNA sequencing results revealed that genes involved in nervous system development and metabolism were significantly different between HT and CON groups. Conclusion: Daily application of heat therapy for two weeks prior to the AVF surgery has beneficial effects on both skeletal muscle contractile and mitochondrial function suggesting this pre-habilitation strategy may mitigate the risk of ARHD in patients undergoing AVF surgery. Funding Support: National Institutes of Health grant R01HL148597 and American Heart Association grant POST903198. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.