Hemodialysis Vascular Access Dysfunction Research Articles

#2979 Patients referred to nephrology consultation from African countries of Portuguese official language: a Portuguese single-center cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is a main cause of morbidity and mortality worldwide, with African population being at increased risk. Nevertheless, access to treatment for CKD is restricted in African countries resulting in premature death. The latest statistics point to an annual referral to Portugal of around 900 patients from those countries for medical reasons—of which only 5% corresponds to Nephrology referrals. However, this protocol is burdened with high social and economic impact, consuming 50% of the funds budgeted by the Portuguese government (estimated at 3 million euros annually). The aim of this study was to describe the clinical characteristics, reasons for the referral and outcomes of patients from African Countries of Portuguese Official Language (ACPOL) to a nephrology consultation in a tertiary hospital in Portugal under a cooperation protocol. Method Single-center retrospective analysis of 131 African patients referred to our nephrology department between 2014 and 2023. Results Only 84 patients (64%) ended up being evacuated from their country of origin and attended the nephrology consultation in Portugal. The mean age was 46 ± 14 years and 55% were male. Thirty-two patients were from Guinea-Bissau (38%), 24 from São Tomé and Príncipe (29%), 22 from Cape Verde (26%), and 6 from Angola (7%). The motives for referral to a tertiary center were advanced CKD in 58 patients (69%), nephrotic syndrome in 21 patients (25%), and hemodialysis (HD) vascular access dysfunction in 5 of the cases (6%). In the group of patients referred with advanced CKD the mean eGFR was 16 ± 10 ml/min, all patients had hypertension, 20% had diabetes and 9% presented heart failure. More than half (56%) needed hospitalization with urgent need of dialysis and all patients started HD with a central venous catheter. During the follow-up, four patients died (5%), two patients (2.3%) transitioned to peritoneal dialysis and 70% were on kidney transplant waiting list. Patients referred with nephrotic syndrome had a mean eGFR of 71 ± 49 ml/min/1,73 m2 and a median urine albumin/creatinine ratio (uACR) of 6.9 [IQR 4.7-8.8] g/g. Kidney biopsy was performed in 90% of the cases, with membranous nephropathy (37.5%) and focal segmental glomerulosclerosis (25%) being the two most frequent diagnosis. Only two patients returned to their origin country; the remaining prolonged their stay due to unavailability of resources for appropriate treatment in their country of origin. Conclusion These data emphasize the inequality in access to healthcare in African countries and highlights the urgent need for investment, especially in CKD, as it contributes to serious consequences in these patients’ survival and morbidity. With the cooperation protocol, Portugal provides the possibility for these patients to be evacuated and treated in specialized nephrology departments, improving their outcomes. However, our study shows that there is still a lot to be done since just over 60% of referred patients manage to reach Portugal. The entire evacuation process remains extremely delayed, a fact shown by the need for patients to start urgent HD and that more than half of them require hospitalization upon arrival at the nephrology department, with a high economic burden.

Angioplasty for dysfunctional arteriovenous fistulas: A meta-analysis of recent randomized controlled trials compared paclitaxel-coated balloon versus conventional balloon angioplasty.

Stenosis in arteriovenous fistulas (AVF) due to neointimal hyperplasia is one of the most common causes of hemodialysis vascular access dysfunction. Treating patients with dysfunctional AVF with drug-coated balloon (DCB) angioplasty may potentially improve outcomes. This systematic review aimed to compare the effectiveness and safety of DCB angioplasty versus conventional balloon angioplasty by pooling evidence from the most recent randomized controlled trials. We conducted a comprehensive literature search in the Web of Science, Embase, and Cochrane central databases. Two independent researchers screened the article, extracted interest, and evaluated included studies for risk of bias. Pooled estimation was conducted in terms of 6-month target-lesion primary patency (TLPP) and target-lesion reintervention (TLR), as well as other outcomes. Results were expressed with odds ratio (OR) and 95% confidence interval (CI). A total of five RCTs were identified and included in the meta-analyses, with 1107 participants. DCB has a trend of a higher rate of TLPP (OR 1.79, 95% CI 0.66-4.90, p = 0.181) and a significantly lower rate of TLR (0.52, 95% CI 0.29-0.92, p = 0.034), as compared to conventional balloon angioplasty. No difference in the 6-month access circuit primary patency and reinvention was observed between the two groups. DCB may be an alternative treatment of dysfunctional AVF given a trend of a higher rate of TLPP and a significantly lower rate of TLR than conventional balloon angioplasty within 6 months after the indexed procedure. Moreover, DCB was non-inferior to conventional balloon angioplasty in terms of safety. Considering variations in the DCB technique, further studies are warranted for a standardized process.

Contrast Venography Versus Intravenous Ultrasound in Hemodialysis Arteriovenous Access Dysfunction

Contrast Venography Versus Intravenous Ultrasound in Hemodialysis Arteriovenous Access Dysfunction

Optimization of a local type rabbit model for arteriovenous fistula, focused on study neointimal hyperplasia

Link of Video Abstract: https://youtu.be/8kcI8mX5A6Y Background: Hemodialysis vascular access dysfunction is a significant cause of morbidity and mortality in hemodialysis patients. Over the past decades, numerous animal models have been developed. However, there needs to be more animal model protocol with rabbits to investigate neointimal hyperplasia in the arteriovenous fistula. This study aimed to explore an alternative rabbit model using a wild-type local model for investigating neointimal hyperplasia in the arteriovenous fistula. Methods: One local-type male rabbit performed arteriovenous fistula, in which the right carotid communis artery was anastomosed end-to-side to the right internal jugular vein. When examining vascular tissue, measurements were taken of the thicknesses of the tunica intima and tunica media, as well as the areas of the tunica intima and tunica media, vascular diameters, and vascular lumen areas. Result: We successfully induced neointimal hyperplasia in local-type rabbits, indicated by increased tunica intima thickness after 28 days of the arteriovenous fistula procedure. Conclusion: Optimation of the Rabbit model using a wild-type local model for investigating neointimal hyperplasia in arteriovenous fistula may be susceptible and considered as it is accessible and cost-effective besides producing the same outcome as a laboratory rabbit

Western and Traditional Chinese Medicine's Perspective on Hemodialysis Vascular Access Dysfunction

<p>血液透析血管通路功能障礙是醫護人員及病人十分重視的議題。近年的醫學研究顯示，血管通路功能障礙的核心機轉為血管重塑、新內膜增生。部分研究指出應用中醫護理方法於血管通路照護，能改善血管通路的併發症及促進成熟。本文梳理西醫和中醫的觀點，彙整血管通路功能障礙的機制，期能對未來發展血液透析血管通路中西醫結合照護方案有所啟發。</p> <p> </p><p>Hemodialysis vascular access dysfunction is an important issue for both patients and medical professionals. Studies have shown that integrating traditional Chinese medicine and nursing care of vascular access for hemodialysis can reduce vascular access complications and promote arteriovenous fistula maturity. </p> <p>This article aims to review literatures regarding the Western and traditional Chinese medicine on pathogenesis and pathology of vascular remodeling and neointimal hyperplasia in the setting of hemodialysis vascular access dysfunction, and to inspire the future development of the integrative Western and traditional Chinese medical nursing care programs for hemodialysis vascular access.</p> <p> </p>

Association of Permanent Vascular Access Dysfunction with Subsequent Risk of Cardiovascular Disease: A Population-Based Cohort Study.

A functional permanent vascular access (VA) is required to perform a successful hemodialysis procedure. Hemodialysis VA dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population. Cardiovascular disease (CVD) is the leading cause of death in patients receiving chronic hemodialysis. Information about CVD associated with hemodialysis VA dysfunction is unclear. We analyzed the association between dialysis VA dysfunction and the risk of developing CVD in hemodialysis patients. This nationwide population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan. One million subjects were sampled from 23 million beneficiaries and data was collected from 2000 to 2013. Patients with end-stage renal disease who had received permanent VA construction and hemodialysis and were aged at least 20 years old from 2000 to 2007 were included in the study population. The primary outcome was CVD, as defined by ICD-9-CM codes 410–414 and 430–437. A total of 197 individuals with permanent VA dysfunction were selected as the test group, and 100 individuals with non-permanent VA dysfunction were selected as the control group. Compared with the control group, the adjusted hazard ratio of CVD for the VA dysfunction group was 3.05 (95% CI: 1.14–8.20). A Kaplan–Meier analysis revealed that the cumulative incidence of CVD was higher in the permanent VA dysfunction group than in the comparison group. Permanent VA dysfunction is significantly associated with an increased risk of subsequent CVD.

Drug-coated balloon versus conventional balloon angioplasty of hemodialysis arteriovenous fistula or graft: A systematic review and meta-analysis of randomized controlled trials.

BackgroundRestenosis remains a significant problem in endovascular therapy for hemodialysis vascular access. Drug-coated balloon (DCB) angioplasty decreases restenosis in peripheral and coronary artery diseases. The aim of this systematic review and meta-analysis is to assess the patency outcomes following DCB angioplasty, as compared to conventional balloon (CB) angioplasty for the stenosis of hemodialysis vascular access.MethodsA comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases was conducted in order to identify eligible randomized controlled trials evaluating DCB angioplasty for hemodialysis vascular access dysfunction. The primary endpoint was the 6-month target lesion primary patency and the secondary endpoints were 12-month target lesion primary patency and procedure-related complications. Risk ratios (RR) were pooled and relevant subgroups were analyzed separately.ResultsEleven randomized controlled trials comprised of 487 patients treated with DCB angioplasty and 489 patients treated with CB angioplasty were included. There were no significant differences in the target lesion primary patency at 6 months [RR, 0.75; 95% confidence interval (CI), 0.56, 1.01; p = 0.06] and at 12 months (RR 0.89; 95% CI, 0.79, 1.00; p = 0.06). The absence of benefit for the DCB group remained, even in the arteriovenous fistula subgroup or the subgroup of studies excluding central vein stenosis. The risk of procedure-related complication did not differ between the two groups (RR 1.00; 95% CI 0.98, 1.02; p = 0.95).ConclusionDCB angioplasty did not demonstrate significant patency benefit for the treatment of hemodialysis vascular access dysfunction. Wide variations in patency outcomes across studies were noted. Further studies focusing on specific types of access or lesions are warranted to clarify the value of DCB for hemodialysis vascular access. (PROSPERO Number CRD42019119938)

Flexible, Skin Coupled Microphone Array for Point of Care Vascular Access Monitoring.

Point-of-care screening for hemodialysis vascular access dysfunction requires tools that are objective and efficient. Listening for bruits during physical exam is a subjective examination which can detect stenosis (vascular narrowing) when properly performed. Phonoangiograms (PAGs)-mathematical analysis of bruits-increases the objectivity and sensitivity and permits quantification of stenosis location and degree of stenosis (DOS). This work describes a flexible and body-conformal multi-channel sensor and associated signal processing methods for automated DOS characterization of vascular access. The sensor used an array of thin-film PVDF microphones integrated on polyimide to record bruits at multiple sites along a vascular access. Nonlinear signal processing was used to extract spectral features, and cardiac cycle segmentation was used to improve sensitivity. PAG signal processing algorithms to detect stenosis location and severity are also presented. Experimental results using microphone arrays on a vascular access phantom demonstrated that stenotic lesions were detected within 1cm of the actual location and graded to three levels (mild, moderate, or severe). Additional PAG features were also used to define a simple binary classifier aimed at patients with failing vascular accesses. The classifier achieved 90% accuracy, 92% specificity, and 91% sensitivity at detecting stenosis greater than 50%. These results suggest that point-of-care screening using microphone arrays can identify at-risk patients using automated signal analysis.

Mineralocorticoid receptor: A hidden culprit for hemodialysis vascular access dysfunction.

Hemodialysis vascular access dysfunction is a common and intractable problem in clinical practice with no definitive therapy yet available. As a key mediator of vascular and cardiac maladaptive remodeling, mineralocorticoid receptor (MR) plays a pivotal role in vascular fibrosis and intimal hyperplasia (IH) and is potentiated locally in hemodialysis vascular access following diverse injuries, like barotrauma, cannulation and shear stress. MR-related genomic and non-genomic pathways are responsible for triggering vascular smooth muscle cell activation, proliferation, migration and extracellular matrix overproduction. In endothelial cells, MR signaling diminishes nitric oxide production and its bioavailability, but amplifies reactive oxygen species, leading to an inflammatory state. Moreover, MR favors macrophage polarization towards a pro-inflammatory phenotype. In clinical settings like post-angioplasty or stenting restenosis, the beneficial effect of MR antagonists on vascular fibrosis and IH has been validated. In aggregate, therapeutic targeting of MR may provide a new avenue to prevent hemodialysis vascular access dysfunction.

Tryptophan-Derived Uremic Toxins and Thrombosis in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) display an elevated risk of thrombosis. Thrombosis occurs in cardiovascular events, such as venous thromboembolism, stroke, and acute coronary syndrome, and is a cause of hemodialysis vascular access dysfunction. CKD leads to the accumulation of uremic toxins, which exerts toxic effects on blood and the vessel wall. Some uremic toxins result from tryptophan metabolization in the gut through the indolic and the kynurenine pathways. An increasing number of studies are highlighting the link between such uremic toxins and thrombosis in CKD. In this review, we describe the thrombotic mechanisms induced by tryptophan-derived uremic toxins (TDUT). These mechanisms include an increase in plasma levels of procoagulant factors, induction of platelet hyperactivity, induction of endothelial dysfunction/ impairment of endothelial healing, decrease in nitric oxide (NO) bioavailability, and production of procoagulant microparticles. We focus on one important prothrombotic mechanism: The induction of tissue factor (TF), the initiator of the extrinsic pathway of the blood coagulation. This induction occurs via a new pathway, dependent on the transcription factor Aryl hydrocarbon receptor (AhR), the receptor of TDUT in cells. A better understanding of the prothrombotic mechanisms of uremic toxins could help to find novel therapeutic targets to prevent thrombosis in CKD.

Substitution-rate based screening model to assess stenosis progression in experimental stenotic arteriovenous grafts.

An arteriovenous graft (AVG) has a higher patency rate in stenosis progression at the venous anastomosis site, which causes coexisting inflow and outflow stenoses. This leads to increases in blood pressure, flow velocity, and flow resistance, resulting in hemodialysis (HD) vascular access dysfunction from early clots and thrombosis to the progression of coexisting stenoses. To prevent vascular access complications such as inflow or outflow stenoses, this study proposes a novel examination method in an experimental AVG system using a substitution-rate based screening model. In our practical measurements, we found that inflow and outflow channeled through a narrowed access indicated both pressure and resistance differences as the degree of stenosis (DOS) gradually increased. A substitution-rate matrix was conducted to replace bilateral pressure variations, while a transition probability matrix was calculated. Differences in transition probabilities were then used to distinguish between normal conditions and flow instabilities using the distance estimation method. The joint probability decayed from < 0.81 to 0.00 could be specified to identify the progression in stenosis levels from a DOS% = 50.0-95.0%. Average joint probabilities were found to be inversely related with the DOS using a non-linear regression (R>2 0.90). Hence, the joint probability could be specified as a critical threshold, < 0.81, to identify the severity stenosis level, DOS% ⩾ 70%, in the assessment of coexisting inflow and outflow stenoses. Experimental results suggest that the proposed model is superior to hemodynamic analysis and traditional intelligent method, and can be used for dysfunction screening during HD treatment.

Efficacy of statin on vascular access patency in diabetic hemodialysis patients.

An effective approach to prevent hemodialysis vascular access dysfunction is still unclear despite previous studies, which have shown conflicting results of several drugs on vascular access outcomes. In this study, we focused on diabetic hemodialysis patients with native arteriovenous fistula and evaluated the impact of statin treatment on vascular access patency. A retrospective cohort study of 268 consecutive patients who newly started hemodialysis due to diabetic nephropathy between January 2011 and December 2013 at Japan Community Health Care Organization Sendai Hospital was performed and the patients were followed for two years. The primary outcome was vascular access dysfunction. Effect of statin treatment was examined using Kaplan Meier analysis and Cox proportional hazard, after adjusting for covariates. The mean follow-up period was 426.7 days, and 117 (52.2%) patients developed vascular access dysfunction. The two-year patency rate was 55.0% among statin users and 36.1% in non-users. Vascular access survival period was significantly longer among statin users (log-rank test, p = 0.004). In multivariable analysis, statin treatment is significantly associated with better vascular access outcomes, in which the hazard ratio was 0.71 (95% CI, 0.52 to 0.97; p = 0.028) in the unadjusted model and 0.63 (95% CI, 0.45 to 0.88; p = 0.007) after adjustment for covariates. Statin treatment could be associated with improved vascular access dysfunction among diabetic hemodialysis patients.

Effectiveness of beraprost sodium in maintaining vascular access patency in patients on hemodialysis.

Hemodialysis vascular access dysfunction, mostly attributed to neointimal hyperplasia, is a major cause of morbidity and hospitalization in patients on hemodialysis. It has been reported that prostaglandin I2 has pleiotropic effects including anti-platelet, vasodilating, anti-inflammatory, and anti-atherogenic properties. In addition, several studies have shown that prostaglandin I2 can inhibit neointimal formation after vascular injury. This study aimed to investigate the effects of beraprost sodium, an oral synthetic analog of prostaglandin I2, on vascular access patency in patients on hemodialysis who experienced primary hemodialysis vascular access failure. Fifty-five patients with end-stage renal disease who were on hemodialysis were prospectively selected for this study. Twenty-three patients were assigned to be treated with 120µg/day of beraprost sodium, while remaining patients (n=32) were assigned to a control group. The primary outcome was primary unassisted vascular access patency at 2years. The incidence of primary unassisted patency at 2years was 83% in the beraprost sodium group and 38% in the control group (p=0.001). Analysis of covariables indicated that this effect occurred mainly as a result of beraprost sodium administration. No life-threatening adverse event or severe bleeding was recorded in any of the groups. Our data indicated that an oral prostaglandin I2 analog, beraprost sodium, is effective and safe for the maintenance of vascular access patency in patients on hemodialysis with primary vascular access failure.

Vascular Access Calcification and Arteriovenous Fistula Maturation

The vascular access serves as the “lifeline” for the hemodialysis patient, but in recent years has become the “Achilles Heel” of the hemodialysis procedure. The vascular health of the vessels used to create arteriovenous accesses is paramount to vascular access maturation and successful outcomes. Vascular calcification is widely present in the vessels of chronic kidney disease (CKD) and end stage renal disease (ESRD) patients, and may also potentially impact the vascular access remodeling process. Few studies have been published to date evaluating vascular calcification as it relates to vascular access outcomes. However, an improved understanding of how vascular calcification plays a pathophysiological role in hemodialysis vascular access dysfunction may improve therapies to treat arteriovenous fistula (AVF) non-maturation and the health of the vessels prior to vascular access creation.

Novel Therapies for Hemodialysis Vascular Access Dysfunction

Hemodialysis vascular access dysfunction is a major source of morbidity for patients with ESRD. Development of effective approaches to prevent and treat vascular access failure requires an understanding of the underlying mechanisms, suitable models for preclinical testing, systems for targeted delivery of interventions to maximize efficacy and minimize toxicity, and rigorous clinical trials that use appropriate outcome measures. This article reviews the substantial progress and ongoing challenges in developing novel treatments for arteriovenous vascular access failure and focuses on localized rather than systemic interventions.

The Transcription Factor E26 Transformation–Specific Sequence-1 Mediates Neointima Formation in Arteriovenous Fistula

Hemodialysis vascular access dysfunction contributes to increased morbidity and mortality in hemodialysis patients. Arteriovenous fistula (AVF) is the preferred type of vascular access for hemodialysis but has high rates of dysfunction, in part because of excessive neointima formation. The transcription factor E26 transformation-specific sequence-1 (ETS-1) is a mediator of proinflammatory responses in hypertension and endovascular injury. We examined the role of ETS-1 in the formation of neointima in AVF. Right carotid artery to internal jugular vein fistulas were created in C57BL/6 mice and assigned to treatment with an ETS-1-dominant negative peptide (ETS-DN), an inactive mutant peptide (ETS-MU), or vehicle (n=6 per group). After 7 and 21 days, AVFs or contralateral internal jugular veins were processed for PCR, immunofluorescence, immunohistochemistry, and morphometry. In AVFs, ETS-1 mRNA increased 2.5-fold at 7 days and 4-fold at 21 days. By immunofluorescence, we confirmed increased expression of ETS-1 predominantly in the neointima and overlying endothelium. Similarly, ETS-1 expression increased in human AVFs compared with normal veins. In mice, ETS-DN, but not ETS-MU, reduced neointima formation at days 7 and 21 and reduced the expression of nitric oxide synthase 2, NADPH oxidase (NOX) 2, NOX4, E-selectin, and monocyte chemotactic protein-1. Shear stress increased ETS-1 phosphorylation in human umbilical vein cells in a NOX-dependent manner, demonstrating a role for reactive oxygen species in ETS-1 activation. These results unveil the role of ETS-1 as a mediator of neointima formation in AVF and may result in the development of novel strategies for the treatment of AVF dysfunction.

Balloon Cinch Deformity during Angioplasty Procedures: An Indication for Impending Rupture

Percutaneous transluminal balloon angioplasty (PTA) is a commonly performed procedure for hemodialysis vascular access dysfunction including thrombosis. While PTA is generally safe, balloon rupture during the procedure is a potential complication. Because such a rupture can cause damage to the blood vessel, indication of an imminent balloon rupture might help avoid such a complication. This analysis reports on six PTA procedures that were complicated by balloon rupture. All cases demonstrated terminal (caudal/cranial) cinch deformation. There was a loss of sharp terminal tapering and its replacement with banana silhouette before the balloon rupture. Importantly, the contour deformation and balloon rupture occurred at a pressure that was lower than the rated burst pressure. The cinch deformity can be used as an indication for impending balloon rupture. We suggest deflation of balloons that demonstrate shape deformations to avoid vascular injury.

Superoxide in AVF dysfunction: a new target for intervention

an adequately functioning vascular access is an absolute requisite for patients receiving hemodialysis. Among the three currently available (fistulae, grafts, and tunneled catheters) vascular accesses, the arteriovenous fistula (AVF) is considered the “gold standard” and is the most common mode

Hemodialysis Vascular Access Dysfunction: Molecular Mechanisms and Treatment

Hemodialysis vascular access complications are one of the main causes associated with an increase in morbidity and hospitalization in hemodialysis (HD) patients. The most common cause of vascular access dysfunction is venous stenosis as a result of venous neointimal hyperplasia within the peri-anastomotic region (arteriovenous [AV] fistula) or at the graft-vein anastomosis. There have been few studies regarding effective therapeutic interventions for HD vascular dysfunction at the present time, despite the magnitude of the clinical problem. This review will focus initially on the pathology and pathogenesis of HD vascular access dysfunction in the setting of both native AV fistula and polytetrafluoroethylene (PTFE) graft, then experimental and clinical therapies that could potentially be used in the setting of HD vascular access dysfunction.

Radiation Therapy for Dialysis Access Stenosis: Unfulfilled Promise or False Expectations

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population at a cost of well over $1 billion per annum. Venous stenosis (due to venous neointimal hyperplasia [VNH]) is the most common cause of polytetrafluroethylene PTFE) dialysis access graft and arteriovenous fistula (AVF) failure. Despite the magnitude of the clinical problem, however, there are currently no effective therapies for this condition. We and others have previously demonstrated that VNH in PTFE dialysis grafts and AVF is composed of smooth muscle cells/myofibroblasts, endothelial cells within neointimal microvessels, and peri-graft macrophages. Radiation therapy blocks the proliferation and activation of all these cell types. The current review will dissect out the available in vitro, experimental, and clinical data on the use of radiation therapy for vascular stenosis in general, and for dialysis access dysfunction in particular. It is important to try and identify whether there is still a role for radiation therapy in this specific clinical setting. We believe that this is a critically important question to answer in view of the huge unmet clinical need that is currently associated with hemodialysis vascular access dysfunction.