Arteriovenous Fistula Stenosis Research Articles

The efficacy of paclitaxel drug-eluting balloon angioplasty versus standard balloon angioplasty in stenosis of native hemodialysis arteriovenous fistulas

Abstract Background End stage renal disease is on increasing trend and haemodialysis is the main dialysis modality among these patients. Thus, a functioning dialysis vascular access is critical to the delivery of life-saving haemodialysis treatment to these patients. Conventional angioplasty is the first line of treatment; with a 50% of permeability rate (6 months). For this reason, new alternatives are necessary to maintain the access permeability.Hypothesis: Paclitaxel coated balloon is superior to conventional plain balloon angioplasty with decreased re-stenosis of target lesion, improved access circuit and target lesion patency, and decreased number of interventions needed to maintain patency. Methods A total of 39 patients were randomized to receive a paclitaxel-coated balloon (n=15) or plain angioplasty balloon (n=24) after satisfactory angioplasty with a high-pressure balloon. The inclusion criteria were clinical signs of vascular dysfunction confirmed by Doppler Ultrasound and/or angiography. The primary endpoint was target lesion patency defined as time elapsed between the completion of effective and the appearance of restenosis at 3, 6 and 12 months after angioplasty. Secondary endpoints included the relationship between the location of the stenosis, previous angioplasty, demographic variables and survival. Results We recruited 39 patients with dysfunctional vascular accesses; 24 were assigned to the conventional balloon angioplasty group and 15 drug-eluting balloon angioplasty (paclitaxel). With demographic characteristics in Table I. In group A, all were autologous acces. Group B 16% (4) of the accesses were prosthetic and 84% (20) autologous. In relation to the type and length of stenosis, group A was more frequent at the level and longer, whereas in group B it predominated in the central type and less than 20 mm.In our study, we also observed a high rate of total occlusions, frequently in central vessels in group B, while in group A, where peripheral vessels were predominant, total occlusion was less frequent. Table II. We had no complications in either group, and dialysis was immediate at the end of the procedure. Group A did not present restenosis. Table III. Table III shows DEB group (15p) with 100% of permeability according to follow-up and only one (1/15) of patients died due to myocardial infarction and cerebrovascular accident and this patient kept lasted 9 months without restenosis In Table IV. Group B had 2 (8%) patients with restenosis so it was necessary to reoperate using a drug eluting balloon and until now there is no restenosis. From this group we do not have mortality. One patient 1 (24%) had a recovered infarction. Conclusions Paclitaxel-coated balloon angioplasty resulted in superior survival of dysfunctional peripheral vascular access at 12 meses. Both arms show equivalent complications and similar mortality Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Enrique Garcés Hospital

Real-World Efficacy of Paclitaxel-Coated Balloons (P-DCB) in the Treatment of Initial and Recurrent Arteriovenous Fistula (AVF) Stenosis

Real-World Efficacy of Paclitaxel-Coated Balloons (P-DCB) in the Treatment of Initial and Recurrent Arteriovenous Fistula (AVF) Stenosis

C-ARM Guided Angiogram/Angioplasty for Selected Failed Arterio Venous Fistula. A Report of a Procedure at University Hospital of Nepal

End Stage Renal Disease is a last stage of Chronic Kidney Disease which is characterized by Glomerular Filtration rate of less than 15 ml/min/1.73 m2. Hemodialysis is the most commonly used modality for treatment of Chronic Kidney disease. Among the access for hemodialysis arteriovenous fistula is the most common modality. However most common problems of fistula are significant stenosis of more than 50% which is characterized by limb swelling, pigmentation, tortuous veins, and difficulty maintaining flow during dialysis from AV fistula. These can be managed either by minimal intervention or with surgical intervention. Very few hospitals in Nepal and other countries have an angiographic suite to perform minimal intervention include angiogram with angioplasty. So in this case we try to address the use of C-Arm to perform angiogram or fistulogram and even angioplasty for the management of significant stenosis or complications of arteriovenous fistula.

Balloon Assisted Maturation With Large Balloons Should Be First-Line Intervention for Marginal Arteriovenous Fistulas

Balloon assisted maturation (BAM) is a well-established method to develop functional arteriovenous fistulas (AVFs) but often requires multiple reinterventions. To achieve maturation, AVFs must be ∼6 mm in diameter. We hypothesized that larger diameter balloons (8 mm) would be needed to account for recoil during angioplasty and to achieve earlier maturation and a decreased number of interventions. We evaluated the outcomes of initial BAM with large diameter balloons. A retrospective review of 182 patients who had undergone BAM between 2018 and 2020 in an academic medical center was performed. The cohort was divided into two groups. Group I included patients who had undergone initial BAM with an 8-mm balloon (n = 128), and group II included patients who had undergone initial BAM with a <8-mm balloon (n = 54). An 8-mm balloon was not used if extravasation was observed after angioplasty with a smaller balloon. The AVF was considered matured if successfully used for dialysis on three consecutive sessions without further interventions. A total of 234 BAMs were performed: 150 in group I and 84 in group II. All demographics were similar between the two groups. The preprocedure duplex ultrasound showed no differences in the vein size (4.6 ± 1.1 mm vs 3.9 ± 1.2 mm; P = .705), volume flow (705 ± 426 mL/min vs 461 ± 354 mL/min; P = .631), or incidence of AVF stenosis (11.1% vs 1.6%; P = .189) between the two groups. The overall maturation rate was 95% (173 of 182) and was 98.4% in group I and 87% in group II (P = .001). Of the 150 AVFs in group I, 107 (83.5%) achieved maturation after the initial BAM compared with 23 of 84 AVFs (42.5%) in group II (P = .001). The incidence of intraprocedural contrast extravasation and postprocedural hematoma was similar between the two groups (11.7% vs 16.6%; P = .367). None of the complications required intervention nor did they affect AVF patency. The dialysis catheter dwell time was longer in group II than in group I (125 ± 56 days vs 112 ± 42 days; P = .034). The mean AVF diameter after BAM was 6 ± 1.4 mm in group I and 5.1 ± 1.5 mm in group II (P = .992). We conclude that BAM with large diameter balloons is safe and leads to higher AVF maturation rates and fewer reinterventions without an increased rate of complications. It also results in lower catheter dwell times, which might prevent long-term catheter complications. Our data support the theory that larger balloons are needed to achieve a 6-mm AVF diameter owing to vessel recoil after angioplasty.

Arteriovenous fistula formation with adjuvant endovascular maturation

BackgroundThe clinical utility of the native arteriovenous fistula (AVF) has been limited by the prolonged time required for maturation, the low overall maturation rate, and subsequent abandonment. Endovascular intervention has been increasingly accepted as the first-line therapy for AVF stenosis. The objective of the present study was to evaluate the AVF formation outcomes when early endovascular intervention was selectively performed to bring about timely AVF maturation. MethodsWe performed a retrospective study (February 2014 to February 2020) of 82 AVF consecutive patients (mean age, 62.5 ± 13.5 years; range, 17-83; 58 men [70.7%]) with end-stage renal failure who had undergone vascular access construction at a single institution. The 4-year AVF patency, vascular diameters, hemodialysis parameters, reintervention rate, and mortality were analyzed. ResultsRadiocephalic AVF was the most common fistula constructed (71 patients; 88.6%). The evaluation at a mean of 46.2 ± 56.0 days (range, 5-343 days) after AVF formation revealed 33 immature AVFs (40.2%). Subsequently, 19 patients had undergone endovascular procedures, including angioplasty and/or stenting of the juxta-anastomosis, cannulation zones, and/or outflow segments to bring about timely maturation of the AVF. Hence, 93.9% of the AVFs had reached functional patency (maturation) by 6 months after formation, with a mean time to maturation of 67.8 ± 65.9 days (range, 5-320 days). After reaching maturation, the primary access functional patency was 82% ± 4.3% at 6 months, 58% ± 5.5% at 12 months, and 34% ± 6.8% at 48 months. The primary assisted access functional patency was 95% ± 2.4% at 6 months, 90% ± 3.3% at 12 months, and 83% ± 4.7% at 48 months. A total of 121 endovascular interventions were performed to maintain patency, equating to an endovascular reintervention rate of 0.37 procedure/patient year. The mean arterial, venous, and brachial flow rates did not change significantly after maturation with a mean AVF (primary assisted functional patency) survival time of 5.9 ± 0.26 years (range, 5.33-6.36 years) from maturation. Only 12 thromboses had occurred after the first follow-up review after AVF formation. These were all salvaged using endovascular techniques, leading to 100% total secondary functional patency at 4 years. The 5-year estimated all-cause mortality was 45.6% ± 12.7%. ConclusionsThe AVF maturation rate and interval to maturation were improved when early endovascular intervention was selectively performed after AVF formation. This allowed for near universal maturation. In addition, once matured, the use of ongoing endovascular reinterventions allowed for a low reintervention rate and long-term patency, providing reliable long-term renal vascular access.

Plasmatic osteopontin and vascular access dysfunction in hemodialysis patients: a cross-sectional, case–control study (The OSMOSIS Study)

Despite close follow-up of patients with native arteriovenous fistulas (AVFs), up to 10% experience thrombosis each year. The OSMOSIS Study (Osteopontin as a Marker of Stenosis) tested the hypothesis that the systemic osteopontin level, a pro-inflammatory mediator related to vascular remodelling and intimal hyperplasia, increases in AVF stenosis, and may be used in clinical surveillance. Our cross-sectional study compared the level of plasmatic osteopontin (pOPN) between patients with a well-functioning AVF (control group) and patients who required revision of their AVF due to stenosis (stenosis group). Blood samples were collected before dialysis (control group) or before intervention (stenosis group) from the AVF arm, and from the opposite arm as a within-subject control. pOPN level was measured by enzyme-linked immunosorbent assay. A total of 76 patients were included in the study. Baseline characteristics were similar between the groups (mean age, 70years; men, 63%; AVF duration, 39months), apart from prevalence oftype 2 diabetes (T2D) (control group, 33%; stenosis group, 57%; p = 0.04). pOPN levels were similar between the AVF arm and the contralateral arm (551 ± 42ng/mL vs. 521 ± 41ng/mL, respectively, p = 0.11, paired t-test). Patients in the stenosis group displayed a higher pOPN level than patients in the control group (650.2 ± 59.8ng/mL vs. 460.5 ± 61.2, respectively, p = 0.03; two-way ANOVA). T2D was not identified as an associatedfactor in a multivariate analysis (p = 0.50). The levelof pOPN in hemodialysis patients was associated with the presence of AVF stenosis requiring intervention. Thus, its potential as a diagnostic biomarker should be assessed in a vascular access surveillance program.

Relationship Between Arteriovenous Fistula Stenosis and Circulating Levels of Neutrophil Granule Proteins in Chronic Hemodialysis Patients

BackgroundArteriovenous fistula (AVF) stenosis leading to its failure is a major cause of morbidity in hemodialysis patients; however, detailed pathogenesis of AVF stenosis is still under investigation. To date, monocytes/macrophages have been considered pivotal players in chronic inflammation of vascular disease including atherosclerosis and AVF stenosis. However, recent evidence strongly suggests that neutrophils and neutrophil granule proteins are important contributors to vascular disease. The aim of the present study was to evaluate the relationship between AVF stenosis and neutrophil activation by measuring circulating levels of neutrophil elastase (NE) and lactoferrin, enzymes released on neutrophil activation, as well as other inflammation markers including neutrophil counts. MethodsThis was a single-center, prospective observational study conducted on 83 prevalent hemodialysis patients with AVF. Blood levels of biomarkers and sonography (US) measurement were assessed at baseline and 1 year after enrollment. Clinical follow-up continued for one more year (a total of 2 years for each patient) to observe any AVF events. ResultsCirculating levels of both NE and lactoferrin positively correlated with the degree of AVF stenosis. Patients with significant AVF stenosis had older AVFs, higher neutrophil-to-lymphocyte ratio (NLR), and higher circulating levels of NE and lactoferrin. On multivariate logistic regression analysis, both circulating levels of NE and NLR remained independent predictors of significant AVF stenosis. ConclusionsCirculating levels of NE and the NLR were identified as independent predictors of at-risk AVF with significant stenosis. Our data suggest the potential role of neutrophil and innate immunity activation on the development of AVF stenosis.

Effect of far infrared therapy on arteriovenous fistula maturation, survival and stenosis in hemodialysis patients, a randomized, controlled clinical trial: the FAITH on fistula trial

BackgroundAn arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis treatment. After creation many of the AVFs will never mature or if functioning will need an intervention within 1 year due to an AVF stenosis. Studies investigating possible therapies that improves the AVF maturation and survival are scarce. Far infrared therapy (FIR) has shown promising results. In minor single centre and industry supported trials FIR has shown improved AVF maturation and survival. There is a need of a randomized multicentre controlled trial to examine the effect of FIR on the AVF maturation and survival and to explore the possible AVF protective mechanism induced by the FIR treatment.MethodsThis investigator initiated, randomized, controlled, open-labeled, multicenter clinical trial will examine the effect of FIR on AVF maturation in patients with a newly created AVF (incident) and AVF patency rate after 1 year of treatment in patients with an existing AVF (prevalent) compared to a control group. The intervention group will receive FIR to the skin above their AVF three times a week for 1 year. The control group will be observed without any treatment. The primary outcome for incident AVFs is the time from surgically creation of the AVF to successful cannulation. The primary outcome for the prevalent AVFs is the difference in number of AVFs without intervention and still functioning in the treatment and control group after 12 months. Furthermore, the acute changes in inflammatory and vasodilating factors during FIR will be explored. Arterial stiffness as a marker of long term AVF patency will also be examined.DiscussionFIR is a promising new treatment modality that may potentially lead to improved AVF maturation and survival. This randomized controlled open-labelled trial will investigate the effect of FIR and its possible mechanisms.Trial registrationClinicaltrialsgov NCT04011072 (7th of July 2019).

Predictive value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for primary patency of percutaneous transluminal angioplasty in hemodialysis arteriovenous fistula stenosis.

The aim of this study is to investigate the potential association of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula (AVF) stenosis. This study conducted a retrospective review of patients with end-stage renal disease referred for hemodialysis AVF stenosis in one center. The study consisted of 114 patients with significant (significant stenosis was defined as a reduction in the caliber of the fistula vein of > 50% with respect to the non-aneurysmal venous segment). AVF stenosis patients were treated with PTA, with conventional balloon angioplasty. The NLR and PLR were calculated from the pre-interventional blood samples. The patients were classified into two groups: group A, primary patency < 12months (n = 35) and group B, and primary patency ≥ 12months (n = 79). Comparisons between the groups were performed using the Mann-Whitney U test. Kaplan-Meier analysis was performed to compare the factors, NLR and PLR, for association with primary patency AVFs. A receiver-operating characteristic curve analysis was performed to identify the sensitivity and specificity of the NLR and PLR cut-off values in the prediction of primary patency time. There was no difference in gender; age; side of AVF; AVF type; comorbid diseases such as diabetes mellitus and hypertension; or blood parameters such as white cell count, erythrocytes, hemoglobin, neutrophils, lymphocytes, monocytes, eosinophils, basophils, C-reactive protein, NLR, or PLR between the two groups (p > 0.05). There was also no significant difference in the patency rate between the NLR < 4.13 and NLR ≥ 4.13 groups at 12months (NLR cut-off point = 4.13, p = 0.273). There were statistically significant differences between the primary patency rates of the PLR < 187.86 and PLR ≥ 187.86 groups at 12months (PLR cut-off point = 187.86, p = 0.023). The cut-off value for PLR for the determination of primary patency was 187.86, with a sensitivity of 57.0% and specificity of 34.4%. An increased level of PLR may be a risk factor for the development of early AVF restenosis after successful PTA. However, more studies are needed to validate this finding.

Balloon-assisted Maturation With Larger Diameter Balloons Should Be First-line Intervention for Nonmaturing Autologous Hemodialysis Access

Serial balloon-assisted maturation (BAM) is a well-established method to develop functional arteriovenous fistulas (AVFs) but often require multiple reinterventions. We hypothesized that initial BAM with a larger diameter balloon will lead to earlier maturation of AVF and lower rates of reintervention. A retrospective review of 173 consecutive patients who underwent BAM between 2018 and 2020 by a single vascular surgeon at a hospital setting was performed. The cohort was divided into Group I: patients that underwent initial BAM with an 8-mm balloon (n = 121), and Group II: patients that had initial BAM with <8-mm balloon (n = 52). An 8-mm balloon was not used if contrast extravasation was observed after angioplasty with a smaller balloon. Only procedures performed to achieve initial AVF maturation were included, and procedures performed to maintain access patency were excluded. AVF was considered matured if successfully used for dialysis on 3 consecutive sessions. Demographic data, procedural details, and outcomes were compared between the two groups. A total of 222 BAMs were performed: 152 in Group I and 70 in Group II. The overall maturation rate was 99% (172/173). All demographics were similar, with the exception of more women in group II (61.5% vs 35.8%; P = .003). Based on preprocedure duplex, there was no difference in the vein size (4.4 ± 1.2 vs 3.9 ± 1.4 mm; P = .122) and volume flow (723 ± 450 vs 492 ± 370 mL/min; P = .079) between groups. However, higher rate of AVF stenosis was noted in Group II (39.5%) as compared with Group I (17.9%; P = .007). Seventy-nine percent (n = 94) of the AVFs in Group I achieved maturation after the initial BAM as compared with 54.9% (n = 28) in Group II (P = .001). Forty-four percent (n = 23) of patients in Group II required additional procedures to achieve maturation vs 22.3% (n = 27) patients in Group I (P = .001). There was a similar incidence of intraprocedural contrast extravasation and post-procedural hematoma in both groups (10.7% vs 17.3%; P = .23). None of the complications required intervention nor did it impact AVF patency. We demonstrated that utilizing large angioplasty balloons during initial BAM is safe and allows to achieve AVF maturation with fewer number of procedures.

An eighth note.

Venous stenosis is the most common cause of arteriovenous fistula (AVF) failure in hemodialysis patients. For patients with AVF stenosis, the pressure over the antecedent part of the AVF stenotic lesion will increase if arterial inflow is sufficient. We report a chronic hemodialysis patient who received an angiographic examination for the juxta-anastomosis stenosis of his AVF. A unique feature of a collateral venous branch antecedent to the stenotic lesion was noted, resembling a musical sign as the "eighth note." After percutaneous transluminal angioplasty, the eighth note attenuated markedly at once. Of note, the eighth note sign is not seen frequently, and thus we postulate that the formation of an eighth note sign on the radiocephalic fistula should fulfill the following requirements, including a sufficient arterial inflow, an adjacent collateral branch close enough to the arteriovenous anastomosis, a severe juxta-anastomotic stenotic lesion, and an intact ulnar venous drainage system.

A UK Expert Consensus Approach for Managing Symptomatic Arteriovenous Fistula (AVF) Stenosis in Haemodialysis Patients.

Stenoses in mature arteriovenous fistulas (AVFs) are common and can negatively impact on the quality of haemodialysis, the longevity of the AVF and lead to debilitating symptoms. Multiple treatment options exist; however, management can vary between different centres. We aimed to establish multidisciplinary consensus on the optimal stepwise application of interventions based on evidence and consensus. A modified Delphi process was conducted with 13 participants from hospitals across the UK, all of whom have high-volume dialysis access practice. The usual intervention to rectify de novo stenoses of mature AVFs is fistuloplasty, although surgery for inflow segment stenoses is also clinically acceptable. Appropriate first-line interventions include plain old balloon angioplasty or high-pressure balloon angioplasty; if these fail during the fistuloplasty, consider upsizing the balloon, prolonged balloon inflation or using alternative interventions, such as cutting or scoring balloons and ultra-high-pressure balloons. Alternative or subsequent interventions vary by anatomical site and may require additional multidisciplinary team input. For a stenoses recurring between 3 and 12months, it is appropriate to consider interventions used de novo, but with a lower threshold for using drug-coated balloons (DCBs) in all regions and for using stent grafts in all regions but inflow segment. Recurrence after 12months should be treated as a de novo lesion, with DCBs considered if they have been used successfully during previous interventions. These recommendations aim to provide a practical guide to multidisciplinary teams in order to optimise the use of multiple interventions for rectifying AVF stenoses and provide unified evidence-based practice guidelines.

Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model.

Fractalkine receptor 1 (CX3CR1) mediates macrophage infiltration and accumulation, causing venous neointimal hyperplasia (VNH)/venous stenosis (VS) in arteriovenous fistula (AVF). The effect of blocking CX3CR1 using an anti-human variable VHH molecule (hCX3CR1 VHH, BI 655088) on VNH/VS was determined using a humanized mouse in which the human CX3CR1 (hCX3CR1) gene was knocked in (KI). Whole-transcriptomic RNA sequencing with bioinformatics analysis was used on human stenotic AVF samples, C57BL/6J, hCX3CR1 KI mice with AVF and CKD, and in in vitro experiments to identify the pathways involved in preventing VNH/VS formation after hCX3CR1 VHH administration. Accumulation of CX3CR1 and CD68 was significantly increased in stenotic human AVFs. In C57BL/6J mice with AVF, there was increased Cx3cr1, Cx3cl1, Cd68, and Tnf-α gene expression, and increased immunostaining of CX3CR1 and CD68. In hCX3CR1-KI mice treated with hCX3CR1 VHH molecule (KI-A), compared with vehicle controls (KI-V), there was increased lumen vessel area and patency, and decreased neointima in the AVF outflow veins. RNA-seq analysis identified TNF-α and NF-κB as potential targets of CX3CR1 inhibition. In KI-A-treated vessels compared with KI-V, there was decreased gene expression of Tnf- α, Mcp-1, and Il-1 β; with reduction of Cx3cl1, NF-κB, and Cd68; decreased M1, Ly6C, smooth muscle cells, fibroblast-activated protein, fibronectin, and proliferation; and increased TUNEL and M2 staining. In cell culture, monocytes stimulated with PMA and treated with hCX3CR1 VHH had decreased TNF- α, CD68, proliferation, and migration. CX3CR1 blockade reduces VNH/VS formation by decreasing proinflammatory cues.

Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway.

It has been reported that the viability and migration of vascular smooth muscle cells contributes to arteriovenous fistula stenosis. Hydroxysafflor Yellow A (HSYA) has been demonstrated to inhibit the viability and migration of VSMCs by regulating Akt signaling. The present study aimed to investigate the role of HSYA on the viability and migration of human umbilical vein smooth muscle cells (HUVSMCs) following stimulation using serum from rats with chronic renal failure (CRF), and to determine the effects of HSYA on PI3K/Akt signaling. Wistar rats were randomly divided into two groups, control and CRF groups. Serum from each group was collected to stimulate the HUVSMCs. Cell Counting Kit-8 and wound healing assays were performed to assess cell viability and migration, respectively. Flow cytometry analysis was performed to assess apoptosis, and western blot analysis was performed to detect protein expression levels of PI3K and Akt. Nitric oxide (NO) production was measured using the Nitrate/Nitrite assay kit. The results demonstrated that serum from CRF rats significantly enhanced cell viability, migration and apoptosis, the effects of which were reversed following treatment with HSYA. In addition, CRF serum decreased NO and endothelial NO synthase expression, whilst increasing the protein expression levels of PI3K and phosphorylated-Akt in HUVSMCs. Notably, treatment with HSYA markedly restored NO production and inactivated the PI3K/Akt signaling pathway. Furthermore, the PI3K/Akt inhibitor, AMG511, exerted similar effects to HSYA. Taken together, the results of the present study suggest that HSYA suppresses cell viability and migration in the presence of CRF serum by inactivating the PI3K/Akt signaling pathway.

Early Detection of Arteriovenous Fistula Stenosis in Hemodialysis Patients through Routine Measurements of Dialysis Dose (Kt/V)

Background: Monitoring of arteriovenous (AV) fistula to detect hemodynamically important stenosis is crucial for the prevention of AV fistula thrombosis. The aim of our study was to analyze the importance of dialysis dose (Kt/V) during online postdilution hemodiafiltration (HDF) for early detection of AV fistula stenosis. Methods: Hemodialysis patients with AV fistula were included in this study. We compared a group of 44 patients who have undergone fistulography and subsequently percutaneous transluminal angioplasty (PTA) of significant AV fistula stenosis (active group) with a group of 44 age- and sex-matched patients without PTA (control group). Observational time in both groups was the same. Results: All patients had postdilution online HDF using a F5008 dialysis machine, which can measure online single-pool Kt/V. All data were analyzed during the performance of 2056 HDF procedures. In the active group, we found statistically significantly lower values of Kt/V, all 8 weeks before PTA. In the active group, there was a significant improvement in Kt/V in the first (p < 0.001) and second week (p = 0.049) after PTA. Three and 8 weeks after PTA, we did not find any statistically significant difference in Kt/V between both groups (p = 0.114; p = 0.058). Patients in the active group had statistically significantly lower substitution volumes and blood pump flow rates during HDF over the whole observation period before and after PTA. In contrast, there were no differences in venous pressure in the dialysis circuit between both groups throughout the observation period. Conclusion: In hemodialysis patients with AV fistula, treated with online HDF, routine measurements of Kt/V during each HDF are a beneficial, quick, and straightforward method for early detection of hemodynamically significant AV fistula stenosis.

Adventitial delivery of nanoparticles encapsulated with 1\u03b1, 25-dihydroxyvitamin D3 attenuates restenosis in a murine angioplasty model

Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C–C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-μL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson’s trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA.

1α,25-Dihydroxyvitamin D3 Encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas.

Few therapies prevent venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation in arteriovenous fistulas (AVF). Expression of the immediate early response gene X-1 (Iex-1), also known as Ier3, is associated with VNH and stenosis in murine AVFs. The study aimed to determine if local release of Ier3 long-acting inhibitor 1α,25(OH)2D3 from poly(lactic-co-glycolic acid) (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (1,25 NP) could affect VNH/VS formation in a large animal model. Immediately after AVF creation in a porcine model of renal failure, 1,25 NP or vehicle control was injected into the adventitia space of AVF outflow veins. Scanning electron microscopy and dynamic light scattering characterized drug and control nanoparticles. Animals were sacrificed 3 and 28 days later for gene expression, immunohistologic, magnetic resonance imaging and angiography, and ultrasound analyses. Whole transcriptome RNA sequencing with differential gene expression analysis was performed on outflow veins of AVF. Encapsulation of 1α,25(OH)2D3 in PLGA nanoparticles formed nanoparticles of uniform size that were similar to nanoparticles without 1α,25(OH)2D3. The 1,25 NP-treated AVFs exhibited lower VNH/VS, Ier3 gene expression, and IER-3, MCP-1, CD68, HIF-1α, and VEGF-A immunostaining, fibrosis, and proliferation. Blood flow and lumen area increased significantly, whereas peak systolic velocity and wall shear stress decreased. Treatment increased Young's modulus and correlated with histologic assessment of fibrosis and with no evidence of vascular calcification. RNA sequencing analysis showed changes in the expression of genes associated with inflammatory, TGFβ1, and apoptotic pathways. Local release of 1,25 NP improves AVF flow and hemodynamics, and reduces stenosis in association with reduction in inflammation, apoptosis, and fibrosis in a porcine model of arteriovenous fistula.

Arteriovenous shunt stenosis assessment based on empirical mode decomposition and 1D-convolutional neural network: Clinical trial stage

Patients suffering from end-stage renal disease usually receive dialysis therapy. The arteriovenous (AV) shunt is a vital vascular access for achieving sufficient blood flow in the vein during hemodialysis and can be either an arteriovenous fistula (AVF) or an arteriovenous graft (AVG). However, the lumens of dialysis accesses are frequently narrowed by thrombosis, resulting in stenosis at the venous anastomosis site or progression of inflow stenosis at the arterial anastomosis site. A narrowed vascular wall will produce abnormal physical stress and cause turbulent flow and high blood pressure. Hence, murmur sounds will occur around the stenotic site. The auscultation method is a noninvasive technique to detect these sounds as phonoangiograph (PAG) signals. The empirical mode decomposition (EMD) method is used to decompose intrinsic fast and slow oscillation components from PAG signals. In this study, the slow oscillation component containing key spectral energy distributions (< 100, 100–300 Hz, and > 300 Hz) will be used to identify the normal and abnormal conditions for further stenosis level assessment. After extracting key frequency-based features using EMD, 1D convolutional and pooling processes, feature patterns can be extracted from spectral patterns, which can distinguish distinct feature patterns and reduce the dimensions of feature patterns and the number of feature datasets for training the classifier. Next, a convolutional neural network-based classifier is used to assess the stenosis levels at a near venous anastomosis site. Its model can solve nonlinear mapping applications and nonlinear separable classifications, including the normal condition, AVG stenosis, and AVF stenosis. The experimental tests with cross-validation will indicate that the proposed method provides a promising result in clinical trials, including mean recall (%), mean precision (%), mean accuracy (%), and a mean F1 score of 95.35 %, 89.49 %, 86.82 %, and 0.9232, respectively, by offering an automatic procedure for AV shunt stenosis assessment without the need for manual feature extraction and classification.

Inhibition of Lysyl Oxidase with β-aminopropionitrile Improves Venous Adaptation after Arteriovenous Fistula Creation.

The arteriovenous fistula (AVF) is the preferred hemodialysis access for end-stage renal disease (ESRD) patients. Yet, establishment of a functional AVF presents a challenge, even for the most experienced surgeons, since postoperative stenosis frequently occludes the AVF. Stenosis results from the loss of compliance in fibrotic areas of the fistula which turns intimal hyperplasia into an occlusive feature. Fibrotic remodeling depends on deposition and crosslinking of collagen by lysyl oxidase (LOX), an enzyme that catalyzes the deamination of lysine and hydroxylysine residues, facilitating intra/intermolecular covalent bonds. We postulate that pharmacological inhibition of lysyl oxidase (LOX) increases postoperative venous compliance and prevents stenosis in a rat AVF model. LOX gene expression and vascular localization were assayed in rat AVFs and human pre-access veins, respectively. Collagen crosslinking was measured in humans AVFs that matured or failed, and in rat AVFs treated with β-aminopropionitrile (BAPN), an irreversible LOX inhibitor. BAPN was either injected systemically or delivered locally around rat AVFs using nanofiber scaffolds. The major endpoints were AVF blood flow, wall fibrosis, collagen crosslinking, and vascular distensibility. Non-maturation of human AVFs was associated with higher LOX deposition in pre-access veins (N=20, P=0.029), and increased trivalent crosslinks (N=18, P=0.027) in human AVF tissues. Systemic and local inhibition of LOX increased AVF distensibility, while reducing wall fibrosis and collagen crosslinking in rat fistulas. Our results demonstrate that BAPN-mediated inhibition of LOX significantly improves vascular remodeling in experimental fistulas.

Does Static Intra Access Pressure Monitoring of Arteriovenous Fistulas Predicts Intra Access Stenosis?

The initiation of hemodialysis in patients with chronic kidney disease (CKD) requires vascular access formation. The choice of vascular access for individual patient depends on various factors however arteriovenous fistula (AVF) is conventionally considered to be the vascular access of choice. Once hemodialysis is initiated through a mature AVF, there is an ongoing need for surveillance of the AVF to ensure adequate function and prevent vascular access issues among which flow obstruction (both inflow and outflow) remains the most important. AVF stenosis can potentially lead to inadequate dialysis delivery and thrombosis thus leading to access loss. Physical examination and AVF Doppler ultrasonography (DUS) are useful for evaluation of stenosis in the arteriovenous connection and the outflow tract. Periodic assessment of the AVF with Static Intra access Pressure (SIAPR) determination may be a reliable means of predicting vascular access stenosis.&#x0D; Material &amp; Methods A cross sectional study carried out at Department of Nephrology, Fatima Memorial Hospital, Lahore from July 2018 to December 2018. In total 113 patients were included, and all patients underwent SIAPR assessment and Doppler Ultrasound of AVF.&#x0D; Results Mean age of the patients was 56.81±9.38 years, male to female ratio of the patients was 1.8:1. In this study the SIAPR was suggestive of stenosis in 87(76.99%) patients. The sensitivity, specificity and diagnostic accuracy of SIAPR against Doppler US of the AVF for detection of stenosis was 75.86%, 22.62% &amp; 36.28% respectively&#x0D; Conclusion SIAPR has low specificity and diagnostic accuracy compared to Doppler US for detection of AVF stenosis.