Dialysis Vascular Access Dysfunction Research Articles

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 balloons and dialysis vascular access: is there light at the end of the tunnel . . .

This commentary uses the negative results of the PAVE (Paclitaxel-coated Balloons and Angioplasty of Arteriovenous Fistulas) study to (i) discuss the role of drug-coated balloons in the armamentarium of therapies for dialysis vascular access stenosis and (ii) suggest a more patient centered, individualized, and precision medicine-based approach for the future care of patients with dialysis vascular access dysfunction.

A coming of age for vascular access research: the good, the bad, and the ugly!

Dialysis vascular access dysfunction remains an important clinical problem with a very significant morbidity, mortality, and socio-economic cost. Despite the magnitude of the clinical problem, there are currently no truly effective therapies for vascular access dysfunction. Through a high-quality scientific investigation, Liang etal. have identified a number of novel biological pathways responsible for "mouse" arteriovenous fistula stenosis. We hope that the identification of these druggable pathways (targets) will allow for the development of new and effective therapies for vascular access dysfunction, through the creation of an innovation substrate for dialysis vascular access.

Sentinel vascular access monitoring after endovascular intervention predicts access outcome.

The vascular access pressure ratio test identifies dialysis vascular access dysfunction when three consecutive vascular access pressure ratios are >0.55. We tested whether the magnitude of the decline in vascular access pressure ratio 1-week post-intervention could alert of subsequent access failure. The retrospective study included all vascular access procedures at one institution from March 2014 to June 2016. Data included demographics, comorbidities, vascular access features, %ΔVAPR = ((Pre-Post)/Pre] × 100% assessed within the first 2 weeks post-percutaneous transluminal balloon angioplasty, time-to-next procedure, and patency. The log-rank test compared the area under the curve, receiver operating curve, Kaplan-Meier arteriovenous graft and arteriovenous fistula survival curves. A multivariable Cox proportional hazard (CP) model was used to determine the association of %ΔVAPR with access patency. Analysis of 138 subjects (females 51%; Black 87%) included 64 arteriovenous fistulas with 104 angioplasties and 74 arteriovenous grafts with 134 angioplasties. The area under the receiver operating characteristic curve for fistula failure at 3 months was 0.59, with optimal screening characteristics of 33.3%, sensitivity of 56.1%, and specificity of 63.2%. Arteriovenous fistula with <33.3% decline compared to >33.3% required earlier subsequent procedure (136 vs 231 days), lower survival on Kaplan-Meier analysis (P = 0.01), and twofold greater risk of failure (P = .006). Area under the receiver operating characteristic for arteriovenous graft failure at 3 months had a sensitivity of 52.3% and specificity of 67.4%. Arteriovenous graft with a post-intervention vascular access pressure ratio decline of <28.8% also required earlier subsequent procedure (144 vs 189 days), lower survival on Kaplan-Meier (P = 0.04), and a 59% higher risk for failure. The area under the receiver operating characteristic curve for combined access failure (arteriovenous fistula + arteriovenous graft) at 3 months had an optimal cut-point value of 31.2%, a sensitivity of 54.6%, and a specificity of 63.1%. Access with a <31.2% drop had a 62% increase in the risk of failure (hazard ratio 1.62; confidence interval 1.16, 2.27; P = 0.005). The magnitude of post-intervention reduction in vascular access pressure ratio provides a novel predictive measure of access outcomes.

Thrombophilia Associated with Early Post-angioplasty Thrombosis of Dialysis Vascular Access.

Percutaneous transluminal angioplasty (PTA) is widely used as the primary treatment for dialysis vascular access dysfunction. Nonetheless, many patients develop early occlusion after angioplasty. Thus, we investigated the role of thrombophilia in access occlusion within 30days of angioplasty. This case-control study included patients who underwent PTA for dialysis vascular access dysfunction. Patients who experienced occlusion within 30days of angioplasty were included in the case group and those without occlusion for at least 30days after angioplasty were included in the control group. All patients were tested for protein C, protein S, antithrombin III, lupus anticoagulant, and anticardiolipin antibodies. From February to October 2015, 462 patients underwent PTA for dialysis vascular access dysfunction. Forty-one patients (8.9%) had early occlusion within 30days of angioplasty. The case group had more graft accesses (73 vs. 31%, P < 0.001) and thrombotic occlusions (67 vs. 15%, P < 0.001). A higher incidence of protein C (10 vs. 2%), protein S (15 vs. 5%), and antithrombin III (10 vs. 2%) deficiency and elevated anticardiolipin antibody (22 vs. 10%) levels were observed in the case group. Overall, 26 patients (63%) in the case group had at least one thrombophilic factor, compared with 15 patients (37%) in the control group (unadjusted odds ratio [OR], 3.004; 95% confidence interval [CI], 1.223-7.380; P = 0.027). After adjustment for confounding factors, the association between thrombophilic factors and early occlusion remained (adjusted OR, 3.806; 95% CI, 1.018-14.220; P = 0.047). Thrombophilia is associated with early occlusion after angioplasty for hemodialysis vascular access.

Association between Preoperative Vascular Function and Postoperative Arteriovenous Fistula Development.

Arteriovenous fistula (AVF) maturation failure is the primary cause of dialysis vascular access dysfunction. To evaluate whether preoperative vascular functional properties predict postoperative AVF measurements, patients enrolled in the Hemodialysis Fistula Maturation Study underwent up to five preoperative vascular function tests (VFTs): flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, and venous occlusion plethysmography. We used mixed effects multiple regression analyses to relate each preoperative VFT to ultrasound measurements of AVF blood flow rate and venous diameter at 1 day, 2 weeks, and 6 weeks after AVF placement. After controlling for AVF location, preoperative ultrasound measurements, and demographic factors (age, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence interval [95% CI], 3.7% to 25.3%; P<0.01; change in diameter =0.45 mm; 95% CI, 0.25 to 0.65 mm; P<0.001). Greater FMD also associated with greater increases in 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in FMD: change in blood flow rate =11.6%; 95% CI, 0.6% to 23.9%; P=0.04; change in diameter =0.31 mm; 95% CI, 0.05 to 0.57 mm; P=0.02). None of the remaining VFT parameters exhibited consistent statistically significant relationships with both postoperative AVF blood flow rate and diameter. In conclusion, preoperative NMD and FMD positively associated with changes in 6-week AVF blood flow rate and diameter, suggesting that native functional arterial properties affect AVF development.

Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis: A Population-Based Nested Case-Control Study.

The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case-control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186-1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure-response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549-2.186) noted in patients with ≥3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE.

Diagnosis and treatment of insufficient dialysis vascular access.

A wide variety of diagnostic and minimally invasive modalities is currently available to radiologists for providing sufficient medical care for dialysis patients. In addition to clinical examination, ultrasound is the first line imaging method in suspected dialysis vascular access dysfunction. The percutaneous approach is the primarily recommended therapeutic option in many cases. This article reviews the current diagnostic and therapeutic methods in dialysis vascular access insufficiency.

Future directions for vascular access for hemodialysis.

Hemodialysis vascular access is at the same time both the "Lifeline" and the "Achilles Heel" of hemodialysis. This review will initially summarize the vascular biology of dialysis vascular access dysfunction and then use this information to describe some novel and innovative ways (including advances in the process of care for vascular access) to prevent this problem.

Novel Therapeutic Paradigms to Treat Hemodialysis Access Dysfunction

Vascular access dysfunction continues to be a major factor contributor to the morbidity and mortality of hemodialysis patient. Percutaneous intervention has been the central therapeutic modality used to treat dialysis vascular access dysfunction with limited success. Vascular biology research has shed considerable light on the pathophysiologic processes that lead to the development of neointimal hyperplasia, the culprit lesion for vascular access dysfunction, suggesting possible newer novel therapeutic interventions. In this review we discuss; (1) recent advances in the utilization of image based predictive medicine in improving access type selection prior to access creation; (2) current and promising treatment modalities including brachytherapy, gene therapy and pharmacotherapy for prevention of neointimal hyperplasia; (3) alternate imaging modalities during percutaneous endovascular interventions. Though novel therapeutic interventions are evolving, robust clinical studies to identify optimal therapeutic method are needed. A combination of evidenced based interventions from pre access creation up until final abandonment of vascular access is worthy of exploration.

Arteriovenous Fistula Failure: Is There a Role for Epigenetic Regulation?

Epigenetics is the study of heritable changes in gene expression or cellular phenotype that occur without alterations in the DNA sequence. In the past decade, epigenetics has been identified as a key regulator of gene expression and therefore is likely to play a major role in multiple disease processes. More importantly, we now recognize epigenetics to be a sensitive, dynamic, and reversible process that has opened the door to multiple novel diagnostic, prognostic, and therapeutic strategies for human diseases. The focus of this review, however, is to explore the potential role of epigenetics in arteriovenous fistula (AVF) maturation. AVF maturation failure is currently the single most important cause of dialysis vascular access dysfunction and most important is the result of a peri-anastomotic stenosis thought to be caused by a combination of neointimal hyperplasia and inadequate outward remodeling. At a pathogenetic level, however, AVF maturation failure is likely the end result of the interaction between hemodynamic stressors (injury) and the vascular response to these stressors; the latter being influenced by uremia, oxidative stress, and inflammation. Interestingly, these same factors (hemodynamic shear stress, oxidative stress, inflammation, and uremia) are also important mediators of epigenetic modifications. We therefore believe that epigenetic factors potentially could play an important role in the pathogenesis of AVF maturation failure. The current review therefore tries to unravel some of these critical biological connections, with an emphasis on the future development of epigenetic-based diagnostic and therapeutic strategies for AVF maturation failure (a clinical problem for which there are currently no effective therapeutic interventions).

Vascular access in haemodialysis: strengthening the Achilles' heel

Despite all the progress achieved since Scribner first introduced the arteriovenous (AV) shunt in 1960 and Cimino and Brescia introduced the native AV fistula in 1962, we have continued to face a conundrum in vascular access for dialysis, in that dialysis vascular access is at the same time both the 'lifeline' and the 'Achilles' heel' of haemodialysis. Indeed, findings from a multitude of published articles in this area, unfortunately mainly observational studies, reflect both our frustration and our limited knowledge in this area. Despite improved understanding of the pathophysiology of stenosis and thrombosis of the vascular access, we have unfortunately not been very successful in translating these advances into either improved therapies or a superior process of care. As a result, we continue to face an epidemic of arteriovenous fistula (AVF) maturation failure, a proliferation of relatively ineffective interventions such as angioplasty and stent placement, an extremely high incidence of catheter use, and more doubts rather than guidance with regard to the role (or lack thereof) of surveillance. An important reason for these problems is the lack of focused translational research and robust randomized prospective studies in this area. In this Review, we will address some of these critical issues, with a special emphasis on identifying the best process of care pathways that could reduce morbidity and mortality. We also discuss the potential use of novel therapies to reduce dialysis vascular access dysfunction.

From Basic Biology to Randomized Clinical Trial: The Beta Radiation for ArterioVenous Graft Outflow Stenosis (BRAVO II)

The BRAVO-II study was a randomized controlled study of endovascular radiation therapy as compared to sham radiation therapy, following angioplasty of a thrombosed PRFE graft. The results did not show a benefit of endovascular radiation therapy, albeit in the context of an early termination of the study at less than 50% enrollment due to business reasons. Emphasis is laid on the fact that there may still be a role for radiation therapy in specific clinical settings associated with dialysis vascular access dysfunction.

Academic Interventional Nephrology

Dialysis vascular access dysfunction is currently a huge clinical problem. We believe that comprehensive academic-based dialysis vascular access programs that go all the way from basic and translational science investigation to clinical research to a dedicated curriculum and opportunities in vascular access for nephrologists in training are essential for improving dialysis vascular access care. This paper reviews the fundamental concepts and requirements for us to move toward this vision.