Intraoperative transit time flow measurement predicts maturation of radiocephalic arteriovenous fistulas.

OBJECTIVE: The arteriovenous fistula (AVF) is the first choice for gaining vascular access for hemodialysis. However, 20% to 50% of AVFs fail within 4 months after creation. Although demographic risk factors have been described, there is little evidence on the intraoperative predictors of AVF maturation failure. The aim of this study was to assess the predictive value of intraoperative transit time flow measurements (TTFMs) on AVF maturation failure. METHODS: In this retrospective cohort study, intraoperative blood flow, measured using TTFM, was compared with AVF maturation after 6 weeks in 55 patients. Owing to its significantly higher prevalence and risk of nonmaturation, the radiocephalic AVF (RCAVF) was the main focus of this study. A recommended cutoff point for high vs low intraoperative blood flow was determined for RCAVFs, using a receiver operating characteristic curve. RESULTS: The average intraoperative blood flow in RCAVFs was 156 mL/min. Patients with an intraoperative blood flow equal or lower than the determined cutoff point of 160 mL/min, showed a 3.03 times increased risk of AVF maturation failure after 6 weeks, compared with patients with a higher intraoperative blood flow (P < .001). CONCLUSIONS: The intraoperative blood flow in RCAVFs measured by TTFM provides an adequate means of predicting AVF nonmaturation 6 weeks after surgery. For RCAVFs, a cutoff point for intraoperative blood flow of 160 mL/min is recommended for maximum sensitivity and specificity to predict AVF maturation failure after 6 weeks.

Innate and adaptive immune cells associate with arteriovenous fistula maturation and failure.

Creation of arteriovenous fistula (AVF) causes local injury, resulting in immune response of the body and infiltration of immune cells. Acute inflammation is favorable to control inflammation and proceed AVF toward maturation while chronic inflammation in AVF leads to AVF maturation failure. Chronic inflammation in AVF is due to chronic infiltration of immune cells and secretion of inflammatory cytokines. A balance between proinflammatory and anti-inflammatory response is a must for AVF maturation and an overwhelmed proinflammatory infiltrate causes chronic inflammation and AVF failure. As immune cell infiltration plays a critical role in maturation and failure of AVF, it is important to investigate the role of immune cells as well as their density in early and late phase of AVF maturation. The role of inflammation has been discussed in the literature and this review article focuses on the role of pro- and anti-inflammatory immune cells, including macrophages, dendritic cells (DCs), T-cells, and T-regulatory (Treg) cells in AVF maturation and maturation failure.

A new method to determine anastomosis angle configuration for arteriovenous fistula maturation.

Background: The kidneys of patients with chronic kidney disease (CKD) do not function well enough and those in end-stage renal disease (ESRD) of CKD need hemodialysis (HD) as a common renal replacement therapy (RRT) procedure. HD requires a vascular access (VA), and arteriovenous fistula (AVF) is the common VA choice in the world due to its very few complications. Despite the widespread use of AVFs, some risk factors maximize AVF failure, which is accompanied by complications of the patient such as repeating VA surgeries and hospitalization. Therefore, finding effective factors in the success of surgery is highly important and, thus, this study aimed at measuring the effect of anastomosis angle on the success of AVF surgery. Methods: This study evaluated the effect of conducted angle in an AVF anastomosis on AVF maturation. The images of 48 created AVFs for CKD patients was provided over a one-year period (from May 2016 to April 2017). Cross-tab analysis was used, and significance level was considered meaningful at p-value≤0.001. A centralized database was designed to integrate data. A method for image processing was developed and geometrical characteristics of the vessels (such as anastomosis angle) and also the diameter of artery and vein were measured via AutoCAD 2017 software and exported to the database along with other data. Results: The rate of the AVF failure in the studied patients was 8.96%. The anastomosis angle ≤ 30° is preferable from the AVF status point of view because most AVF maturation (or least AVF failure) rates are detected at this range. Conclusion: This study was performed based on a new approach without the need to measure hemodynamic parameters. Moreover, it signified the important role of anastomosis angle in the function of AVF, showing that the anastomosis angle ≤ 30° is a preferable intraoperative recommendation for AVF surgery.

Arteriovenous fistula in dialysis patients: Factors implicated in early and late AVF maturation failure.

Increasing numbers of patients are being diagnosed with end-stage renal disease (ESRD), and the demand for on haemodialysis (HD) is rising. Arteriovenous fistulae (AVFs) remain the best conduit for adequate HD, with fewer complications associated with long-term use compared to bypass grafts and central venous catheters. However, it is known that many newly formed fistulae do not mature to provide useful HD access. The paper provides a narrative overview of factors influencing the process of AVF maturation failure.

Sex Differences in Arteriovenous Fistula Failure: Insights from Bioinformatics Analysis.

(1) Background: Arteriovenous fistulas (AVFs) are the preferred access for hemodialysis. Unfortunately, about 60% of patients, especially female patients, fail to receive normal dialysis within one year after surgery because of AVF failure. However, the underlying mechanisms caused by sex differences in AVF failure remain unclear. (2) Methods: We performed analysis of DEGs and functional analysis with the dataset GSE119296 to reveal the biology underlying AVF failure. Immune responses were calculated using CIBERSORT. A protein-protein interaction network and hub gene were constructed using STRING and stepwise identification of potential drugs was performed online. (3) Results: Functional analysis showed that extracellular matrix reprogramming and PI3K-AKT pathway enrichment were significant in both male and female patients. COL1A1 was the hub gene in male patients, whereas CDK1 was the hub gene in female patients. Immune responses including γδ-T cells and mast cells are activated in female patients while no significant differences were noted in the male group. (4) Conclusions: In this study, we used a series of mature and recognized bioinformatic strategies to determine the following items: (1) Reveal the pathogenesis of AVF failure through HUB genes and signaling pathways between the different sexes. (2) Determine the relationship between sex differences in AVF failure and immune abnormalities. (3) Search for relevant sex-specific drugs targeting AVF failure.

Oxidative stress: An essential factor in the process of arteriovenous fistula failure.

For more than half a century, arteriovenous fistula (AVFs) has been recognized as a lifeline for patients requiring hemodialysis (HD). With its higher long-term patency rate and lower probability of complications, AVF is strongly recommended by guidelines in different areas as the first choice for vascular access for HD patients, and its proportion of application is gradually increasing. Despite technological improvements and advances in the standards of postoperative care, many deficiencies are still encountered in the use of AVF related to its high incidence of failure due to unsuccessful maturation to adequately support HD and the development of neointimal hyperplasia (NIH), which narrows the AVF lumen. AVF failure is linked to the activation and migration of vascular cells and the remodeling of the extracellular matrix, where complex interactions between cytokines, adhesion molecules, and inflammatory mediators lead to poor adaptive remodeling. Oxidative stress also plays a vital role in AVF failure, and a growing amount of data suggest a link between AVF failure and oxidative stress. In this review, we summarize the present understanding of the pathophysiology of AVF failure. Furthermore, we focus on the relation between oxidative stress and AVF dysfunction. Finally, we discuss potential therapies for addressing AVF failure based on targeting oxidative stress.

TLR-4 Inhibition Attenuates Inflammation, Thrombosis, and Stenosis in Arteriovenous Fistula in Yucatan Miniswine.

Arteriovenous fistula (AVF) is the preferred vascular access in hemodialysis patients; however, it is afflicted with a high failure rate. Chronic inflammation, excessive neointimal hyperplasia (NIH), vessel stenosis, early thrombosis, and failure of outward remodeling are the major causes of AVF maturation failure. Inflammatory mediator toll-like receptor (TLR)-4 plays a critical role in NIH, arterial thrombosis, and stenosis. We investigated the effect of TLR-4 inhibition on early thrombosis. Yucatan miniswine were used to create AVF involving femoral artery and femoral vein and treated with TLR-4 inhibitor TAK-242 with ethanol as the vehicle. The vessels were assessed after 12 weeks using histomorphometry, immunostaining, ultrasound, angiography, and optical coherence tomography. Inhibition of TLR-4 attenuated inflammation and early thrombosis in 50% of animals, and blood flow was present through AVF in 25% of animals. Thus, targeting TLR-4 to attenuate inflammation and early thrombosis might be a therapeutic approach to keep AVF patent and maintain blood flow through the outflow vein.

Arteriovenous Fistula Nonmaturation: What's the Immune System Got to Do with It?

Background: Arteriovenous fistula (AVF) nonmaturation is a persistent problem, particularly among female and Black patients. Increasingly, the immune system has been recognized as an important contributor to vascular disease, but few studies have examined immune factors relative to AVF maturation outcomes. This study evaluated the association of serum panel reactive antibodies (PRA), a measure of immune system reactivity assessed in patients undergoing kidney transplant evaluation, with AVF nonmaturation. Methods: We identified 132 patients at our institution who underwent surgical AVF placement between 2010-2019 and had PRA testing within 1 year of AVF creation. Multivariable logistic regression was used to determine the association of patient demographic and clinical factors, class I and class II PRA levels, and preoperative arterial and venous diameters with AVF maturation outcomes. Results: AVF nonmaturation was more likely in females than males (44% versus 20%, P=0.003) and in Black than white patients (40% versus 13%, P=0.001). Class II PRA was higher in females than males (12%±23% versus 4%±13%, P=0.02). In the multivariable model, AVF nonmaturation was associated with class II PRA (adjusted odds ratio [aOR], 1.34 per 10% increase; 95% confidence interval [95% CI], 1.04 to 1.82, P=0.02) and Black race (aOR, 3.34; 95% CI, 1.02 to 10.89, P=0.03), but not with patient sex or preoperative arterial or venous diameters. Conclusions: The association of elevated class II PRA with AVF nonmaturation suggests the immune system may play a role in AVF maturation outcomes, especially among female patients.

Randomized controlled trial of clopidogrel to prevent primary arteriovenous fistula failure in hemodialysis patients.

The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula (AVF). Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure. A double-blind, randomized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients. Ninety three patients were randomized to receive 75 mg/daily of clopidogrel or placebo. The treatment was initiated 7-10 days prior to scheduled access surgery and continued up to six weeks postoperatively, and then patients were monitored for six months. The primary outcome was AVF failure eight weeks after fistula creation. With a permuted block randomization schedule, 46 patients received clopidogrel and 47 patients received control placebo. The primary AVF failures at two months were 21.6% in placebo group and 5.2% in clopidogrel group (P = 0.03). The hazard ratio for the incidence of primary AVF failure was 0.72 (CI 95%, 0.41-1.01). Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration. First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group (P = 0.008). No life-threatening adverse event or severe bleeding was recorded in both groups. Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients.