Search

Approximately 60% of arteriovenous fistulas (AVFs) created in hemodialysis patients in the United States fail to mature. Understanding the underlying pathobiology is requisite to design and implement new treatments. Mechanisms responsible for AVF failure include intimal hyperplasia and poor lumen expansion. Compromised vasoreactivity also might play a role. Our murine AVF model comprises the external jugular vein (EJV) connected to the carotid artery (CA), establishing 3 component parts to the AVF, i.e., proximal CA, EJV, and distal CA. Upon AVF creation, the EJV is acutely exposed to higher pressures and disturbed flow, known causes of endothelial cell dysfunction. First, we tested the hypothesis that endothelial function is impaired in EJVs (193 ± 27 μm i.d.) from AVF mice (i.e., EJV-AVF; n= 5 males and 5 females) vs. EJVs (228 ± 18 μm i.d.) from naïve animals (EJV-Con; n=6 males and 4 females). Three days after creating the AVF, using isometric tension procedures, dose-dependent vasocontraction to the Thromboxane A2 (TxA2) receptor agonist U46619 was robust in the EJV-Con (p Supported by R01HL153244 NIH/NIDDK (TL, YTS, JDS) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Cardiovascular disease is the primary cause of death amongst end-stage renal disease (ESRD) patients. Though arteriovenous fistulas (AVFs) are the access of choice for hemodialysis, joining a high-pressure artery and low-pressure vein leads to cardiac volume overload acutely. Debate exists as to the cardiac ramifications of AVFs, due in part to the difficulty of recruiting ESRD patients and controls for prospective studies. Animal models have been essential in AVF studies, but their usefulness is limited by interspecies differences in physiology and other factors. Thus, we have developed a three-dimensional (3D) cardiac tissue chip with tunable pressure and stretch to model the acute hemodynamic changes associated with AVF creation. Hypothesis: In this study, we aimed to replicate the hemodynamics of murine AVF models in vitro and hypothesized that if 3D cardiac constructs were subjected to “volume overload”, they would display fibrosis and key gene expression changes seen in AVF mice. Methods: Mice underwent either AVF or sham procedure and were monitored for 28 d. Cardiac tissue constructs composed of h9c2 rat cardiac myoblasts and normal adult human dermal fibroblasts in hydrogel were seeded into devices and exposed for 96 h to 100 mmHg/10 mmHg pressure (0.4 s/0.6 s) at 1 Hz. "Systolic" pressure was generated via pneumatic pump while a hydrostatic pressure head gave rise to "diastolic" pressure. The controls were exposed to “normal” stretch while the experimental group was exposed to “volume overload”. Results and Conclusions: The in vitro model yielded similar fibrosis-related gene expression profiles (see figure) and patterns of fibrosis as the murine model.

BACKGROUND: Arteriovenous fistula (AVF) maturation failure is a significant clinical problem in the hemodialysis population. Geometric parameters of human AVFs were associated with AVF development, but causative studies are lacking. We characterized mouse AVF geometry using endothelial nitric oxide synthase (NOS3) mouse models. METHODS: Carotid-jugular AVFs were created in NOS3 overexpression (OE), knockout (KO), and wild type (WT) mice. At 7 and 21 days postcreation, black-blood magnetic resonance images of AVFs were acquired and used to build three-dimensional reconstructions of AVF lumens. We used these reconstructions to calculate the lumen area, lumen centerline, and centerline-derived parameters: anastomosis angle, tortuosity, nonplanarity angle, and location of maximal distance between the feeding artery and AVF vein. Inter- and intrauser variabilities were also determined. RESULTS: When all mice were considered, increased minimum AVF venous lumen area was accompanied by increased venous tortuosity and increased distance between the artery and vein, with both remaining in-plane with the anastomosis. At day 7, the lumen area of AVFs from all strains was 1.5- to 2.5-fold larger than native veins. Furthermore, at day 21, AVF lumen in NOS3 OE (4.04±1.43 mm(2)) was significantly larger than KO (2.74±1.34 mm(2)) (P

Background Preoperative ultrasound mapping is routinely used to select vessels meeting minimal threshold diameters for surgical arteriovenous fistula (AVF) creation but fails to improve AVF maturation rates. This suggests a need to reassess the preoperative ultrasound criteria used to optimize AVF maturation. Methods We retrospectively identified 300 catheter-dependent patients on hemodialysis with a new AVF created between 2010 and 2016. We then evaluated the associations of preoperative vascular measurements and hemodynamic factors with unassisted AVF maturation (successful use for dialysis without prior intervention) and overall maturation (successful use with or without prior intervention). Multivariable logistic regression was used to identify preoperative factors associated with unassisted and overall AVF maturation. Results Unassisted AVF maturation associated with preoperative arterial diameter (adjusted odds ratio [aOR], 1.50 per 1-mm increase; 95% confidence interval [95% CI], 1.23 to 1.83), preoperative systolic BP (aOR, 1.16 per 10-mm Hg increase; 95% CI, 1.05 to 1.28), and left ventricular ejection fraction (aOR, 1.07 per 5% increase; 95% CI, 1.01 to 1.13). Overall AVF maturation associated with preoperative arterial diameter (aOR, 1.36 per 1-mm increase; 95% CI, 1.10 to 1.66) and preoperative systolic BP (aOR, 1.17; 95% CI, 1.06 to 1.30). Using receiver operating curves, the combination of preoperative arterial diameter, systolic BP, and left ventricular ejection fraction was fairly predictive of unassisted maturation (area under the curve, 0.69). Patient age, sex, race, diabetes, vascular disease, obesity, and AVF location were not associated with maturation. Conclusions Preoperative arterial diameter may be an under-recognized predictor of AVF maturation. Further study evaluating the effect of preoperative arterial diameter and other hemodynamic factors on AVF maturation is needed.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for hemodialysis vascular access since 1996. Since the last update in 2006, there has been a great accumulation of new evidence and sophistication in the guidelines process. The 2019 update to the KDOQI Clinical Practice Guideline for Vascular Access is a comprehensive document intended to assist multidisciplinary practitioners care for chronic kidney disease patients and their vascular access. New topics include the end-stage kidney disease "Life-Plan" and related concepts, guidance on vascular access choice, new targets for arteriovenous access (fistulas and grafts) and central venous catheters, management of specific complications, and renewed approaches to some older topics. Appraisal of the quality of the evidence was independently conducted by using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and interpretation and application followed the GRADE Evidence to Decision frameworks. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.

Background: There are very few animal models of balloon angioplasty injury in arteriovenous fistula (AVF), hindering insight into the pathophysiologic processes following angioplasty in AVF. The objective of the study was to develop and characterize a rat model of AVF angioplasty injury. Methods: Balloon angioplasty in 12- to 16-week-old Sprague-Dawley rats was performed at the arteriovenous anastomosis 14 days post-AVF creation with a 2F Fogarty balloon catheter. Morphometry and protein expression of endothelial nitric oxide synthase (eNOS), monocyte-chemoattractant protein-1 (MCP-1), alpha-smooth muscle actin (α-SMA), CD68 (macrophage marker), and collagen expression in AVFs with and without angioplasty were assessed. Results: In AVFs with angioplasty versus without angioplasty: (1) angioplasty increased AVF-vein and artery intimal hyperplasia, (2) angioplasty decreased eNOS protein expression in AVF-vein and artery at 21 days post-AVF creation and remained decreased in the AVF-vein angioplasty group at 35 days, (3) angioplasty increased AVF-vein and artery α-SMA expression within the intimal region at 35 days, (4) angioplasty increased the expression of AVF-vein MCP-1 at 21 days and CD68 at 21 and 35 days, and (5) angioplasty increased AVF-vein and artery collagen expression at 35 days. Conclusion: Our findings describe a reproducible rat model to better understand the pathophysiologic mechanisms that ensue following AVF angioplasty.

Background: Nephrology research is expanding, and harnessing the much-needed information and data for the practice of evidence-based medicine is becoming more challenging. In this study, we used the natural language processing and text mining approach to mitigate some of these challenges. Methods: We analyzed 17,412 abstracts from the top-10 nephrology journals over 10 years (2007–2017) by using latent semantic analysis and topic analysis. Results: The analyses revealed 10 distinct topics (T) for nephrology research ranging from basic science studies, using animal modeling (T-1), to dialysis vascular access-related issues ­(T-10). The trend analyses indicated that while the majority of topics stayed relatively stable, some of the research topics experienced increasing popularity over time such as studies focusing on mortality and survival (T-4) and Patient-related Outcomes and Perspectives of Clinicians (T-5). However, some research topics such as studies focusing on animal modeling (T-1), predictors of acute kidney injury, and dialysis access (T-10) exhibited a downward trend. Conclusion: Stakeholders of nephrology research may use these trends further to develop priorities and enrich the research agenda for the future.

Factors contributing to racial disparities in arteriovenous fistula (AVF) use among hemodialysis (HD) patients remain poorly defined. We evaluated whether the Black/White race disparity in AVF use is affected by vascular access surgeon supply.Using Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb) and Medicare claims data from the US Renal Data System (USRDS), competing risk analyses of all US patients initiating HD with a central venous catheter (CVC) from 2016 to 2017 (Compared with the first (lowest) quartile of surgeon supply, higher supply levels were associated with modestly increased adjusted likelihoods of overall AVF use: 4% (95% CI 1.4%-7.2%), 4% (95% CI 1.4%-7.1%), and 3% (0.0%-6.1%) for second, third, and fourth quartiles, respectively. Although areas with lower surgeon supply had a higher proportion of Black patients, residing in areas with a greater surgeon supply was not significantly associated with a mitigation in racial disparity. Specifically, compared with White patients, Black patients were 10% (95% CI 7%-13%) and 8% (95% CI 5%-11%) less likely to have successful AVF use in lower and higher surgeon supply areas, respectively.Regions with lower surgeon supply had a higher proportion of Black dialysis patients. However, racial disparities in AVF use among patients initiating HD with a CVC were similar in regions with a high and low surgeon supply. Other patient, provider, and practice factors should be evaluated toward mitigating lower rates of AVF use among Black HD patients.

Background: Arteriovenous fistula (AVF) creation may negatively affect cardiac structure and function and impact cardiovascular mortality. The objective of this study was to develop and characterize the cardiac changes following AVF creation in a murine AVF model. Methods: AVFs were constructed using the carotid artery and jugular vein in C57BL/6 mice. Sham-operated AVF mice served as the control group. 2D-echocardiography was performed prior to AVF creation (baseline) and at 7 and 21 days after creation in AVF and sham-operated mice. Picrosirius red was used to stain the left ventricle for collagen production. Results: The cardiac output (CO), left ventricular end diastolic (LVEDD) and systolic (LVESD) diameter, and end-diastolic (LVEDV) and systolic (LVESV) volume was significantly increased at 7 and 21 days in AVF compared to sham-operated mice. There was also a significant increase in CO, LVEDD, LVESD, LVEDV, and LVESV from baseline to 21 days within the AVF group, but not the sham-operated mice. There was a significant decrease in ejection fraction and fractional shortening at 21 days in AVF compared to sham-operated mice. Picrosirius red was significantly more prominent around both the perivascular and interstitial areas of the cardiac tissue from AVF mice compared to sham-operated AVF mice at 21 days. Conclusions: The creation of an AVF in our murine model leads to cardiac changes such as increased cardiac output, left ventricular dilation, and cardiac fibrosis, while showing reductions of ejection fraction and fractional shortening.

Creation of a hemodialysis arteriovenous fistula (AVF) causes aberrant vascular mechanics at and near the AVF anastomosis. When inadequately regulated, these aberrant mechanical factors may impede AVF lumen expansion to cause AVF maturation failure, a significant clinical problem with no effective treatments. The endothelial nitric oxide synthase (NOS3) system is crucial for vascular health and function, but its effect on AVF maturation has not been fully characterized. We hypothesize that NOS3 promotes AVF maturation by regulating local vascular mechanics following AVF creation. Here we report the first MRI-based fluid-structure interaction (FSI) study in a murine AVF model using three mouse strains: NOS3 overexpression (NOS3 OE) and knockout (NOS3−/−) on C57BL/6 background, with C57BL/6 as the wild-type control (NOS3+/+). When compared to NOS3+/+ and NOS3−/−, AVFs in the OE mice had larger lumen area. AVFs in the OE mice also had smoother blood flow streamlines, as well as lower blood shear stress at the wall, blood vorticity, inner wall circumferential stretch, and radial wall thinning at the anastomosis. Our results demonstrate that overexpression of NOS3 resulted in distinct hemodynamic and wall mechanical profiles associated with favorable AVF remodeling. Enhancing NOS3 expression may be a potential therapeutic approach for promoting AVF maturation.

Background: Despite national vascular access guidelines promoting the use of arteriovenous fistulas (AVF) over arteriovenous grafts (AVGs) for dialysis, AVF use is substantially lower in females. We assessed clinically relevant AVF and AVG surgical outcomes in elderly male and female patients initiating hemodialysis with a central venous catheter (CVC). Methods: Using the United States Renal Data System standard analytic files linked with Medicare claims, we assessed incident hemodialysis patients in the United States, 9,458 elderly patients (≥67 years; 4,927 males and 4,531 females) initiating hemodialysis from July 2010 to June 2011 with a catheter and had an AVF or AVG placed within 6 months. We evaluated vascular access placement, successful use for dialysis, assisted use (requiring an intervention before successful use), abandonment after successful use, and rate of interventions after successful use. Results: Females were less likely than males to receive an AVF (adjusted likelihood 0.57, 95% CI 0.52–0.63). Among patients receiving an AVF, females had higher adjusted likelihoods of unsuccessful AVF use (hazard ratio [HR] 1.46, 95% CI 1.36–1.56), assisted AVF use (OR 1.34, 95% CI 1.17–1.54), and AVF abandonment (HR 1.28, 95% CI 1.10–1.50), but similar relative rate of AVF interventions after successful use (relative risk [RR] 1.01, 95% CI 0.94–1.08). Among patients receiving an AVG, females had a lower likelihood of unsuccessful AVG use (HR 0.83, 95% CI 0.73–0.94), similar rates of assisted AVG use (OR 1.05, 95% CI 0.78–1.40) and AVG abandonment, and greater relative rate of interventions after successful AVG use (RR 1.16, 95% CI 1.01–1.33). Conclusions: While AVFs should be considered the preferred vascular access in most circumstances, clinical AVF surgical outcomes are uniformly worse in females. Clinicians should also consider AVGs as a viable alternative in elderly female patients initiating hemodialysis with a CVC to avoid extended CVC dependence.

Worldwide, ESKD prevalence per million population (PMP) has steadily increased from 2003 to 2016 (1), with the greatest proportional increases occurring in lower- and middle-income countries (2). Although dialysis is a lifesaving therapy, it is also extraordinarily expensive, so its use is limited in lower-income countries with less resources available for healthcare. Specifically, the prevalence of dialysis in 2010 was 1176 PMP in higher-income countries, 688 PMP in upper-middle-income countries, 170 PMP in lower-income countries, and 16 PMP in lower-income countries (2). The most common modality of kidney replacement therapy globally is dialysis (78%) and, among patients receiving dialysis, only 11% receive peritoneal dialysis (3). The Kidney360 Global Dialysis Perspective series launched in 2020 and showcases how dialysis is practiced, delivered, and financed in different countries across the world. To date, we have featured perspectives from 17 countries in six continents: Africa (Senegal, South Africa), Asia (India, Israel, Japan, Korea, Singapore, Thailand, Vietnam), Australia, Europe (Spain), North America (Canada, Mexico, United States), and South America (Argentina, Brazil, Guatemala) (4⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓ ⇓–20). Authors of each global perspective were asked to report standard information about their dialysis populations, including general characteristics of the dialysis system and its treatments, such as percentage of patients by dialysis modality, dialysis-unit financing (for profit versus nonprofit), reimbursement (public or private insurance, or self-pay), unit location (hospital versus freestanding), staffing (proportion of nurses versus patient-care technicians and nurse/patient ratios), hemodialysis frequency and session length, and frequency of nephrologist visits. Authors also discussed key challenges and needs unique to their countries, with many discussing potential strategies to improve care moving forward. These perspectives provide fascinating insights about dialysis care in individual countries. Although the availability of dialysis correlates roughly with a country's …

RATIONALE & OBJECTIVE: The current clinical guidelines for vascular access do not have specific recommendations for older hemodialysis patients. Our study aimed to determine the association of age with arteriovenous fistula (AVF) placement, maturation, and primary and secondary patency loss among older hemodialysis recipients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A US national cohort of incident hemodialysis patients 67 years or older (N = 43,851) assembled from the US Renal Data System. EXPOSURE: Age at dialysis initiation. OUTCOMES: AVF placement, maturation, primary patency loss, and abandonment. ANALYTICAL APPROACH: Cause-specific and subdistribution proportional hazards models were used to examine the association of age and AVF outcomes, with kidney transplantation, peritoneal dialysis, and death treated as competing events. Age cutoff was identified by restricted cubic splines. We compared crude and inverse probability–weighted cumulative incidence functions using Gray’s test. RESULTS: As compared with those aged 67

Background and objectives Arteriovenous fistulas are the optimal vascular access type for patients on hemodialysis. However, arteriovenous fistulas are used less frequently in Black than in White individuals. The arteriovenous fistula care continuum comprises a series of sequential steps. A better understanding is needed of where disparities exist along the continuum in order to mitigate racial differences in arteriovenous fistula use. Design, setting, participants, & measurements Using Medicare claims data from the United States Renal Data System, longitudinal analyses of patients ≥67 years initiating hemodialysis with a central venous catheter between July 1, 2010 and June 30, 2012 were performed. Three patient cohorts were identified: patients initiating hemodialysis with a catheter (n=41,814), patients with arteriovenous fistula placement within 6 months of dialysis initiation (n=14,077), and patients whose arteriovenous fistulas were successfully used within 6 months of placement (n=7068). Three arteriovenous fistula processes of care outcomes were compared between Blacks and Whites: (1) arteriovenous fistula creation, (2) successful arteriovenous fistula use, and (3) primary arteriovenous fistula patency after successful use. Results An arteriovenous fistula was placed within 6 months of dialysis initiation in 37% of patients initiating dialysis with a catheter. Among the patients with arteriovenous fistula placement, the arteriovenous fistula was successfully used for dialysis within 6 months in 48% of patients. Among patients with successful arteriovenous fistula use, 21% maintained primary arteriovenous fistula patency at 3 years. After adjusting for competing risks, Black patients on hemodialysis were 10% less likely to undergo arteriovenous fistula placement (adjusted subdistribution hazard ratio, 0.90; 95% confidence interval, 0.87 to 0.94); 12% less likely to have successful arteriovenous fistula use after placement (adjusted subdistribution hazard ratio, 0.88; 95% confidence interval, 0.83 to 0.93); and 22% less likely to maintain primary arteriovenous fistula patency after successful use (subdistribution hazard ratio, 0.78; 95% confidence interval, 0.74 to 0.84). Conclusions Lower arteriovenous fistula use among Blacks older than 67 years of age treated with hemodialysis was attributable to each step along the continuum of arteriovenous fistula processes of care.

Introduction: Impaired venous reactivity has potential to contribute to clinically significant pathologies such as arteriovenous fistula (AVF) maturation failure. Vascular segments commonly used in murine preclinical models of AVF include the carotid artery and external jugular vein. Detailed descriptions of isometric procedures to evaluate function of murine external jugular vein ex vivo have not been previously published. Objective: To establish isometric procedures to measure naive murine external jugular vein reactivity ex vivo. Methods: Vasomotor responses of external jugular veins and ipsilateral common carotid arteries from C57BL/6 mice were evaluated using isometric tension procedures. Results: External jugular veins developed tension (p < 0.05) to potassium chloride and U-46619, but not to phenylephrine, whereas common carotid arteries responded to all 3 agents (p < 0.05). While maximal responses to acetylcholine (ACh) were similar between the venous and arterial segments, the dose required to achieve this value was lower (p < 0.05) in the artery versus vein. Nitric oxide synthase inhibition attenuated (p < 0.05) but did not abolish ACh-evoked vasorelaxation in both vascular segments, whereas cyclooxygenase blockade had no effect. Endothelium-independent vasorelaxation to sodium nitroprusside was similar in the artery and vein. Conclusion: Vasorelaxation and vasocontraction can be reliably assessed in the external jugular vein in C57BL/6 mice using isometric procedures.

Vascular access is the lifeline for hemodialysis patients and the single most important component of the hemodialysis procedure. Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis patients, but nearly 60% of AVFs created fail to successfully mature due to early intimal hyperplasia development and poor outward remodeling. There are currently no therapies available to prevent AVF maturation failure. First, we showed the important regulatory role of nitric oxide (NO) on AVF development by demonstrating that intimal hyperplasia development was reduced in an overexpressed endothelial nitric oxide synthase (NOS3) mouse AVF model. This supported the rationale for the potential application of NO to the AVF. Thus, we developed a self-assembled NO releasing nanomatrix gel and applied it perivascularly at the arteriovenous anastomosis immediately following rat AVF creation to investigate its therapeutic effect on AVF development. We demonstrated that the NO releasing nanomatrix gel inhibited intimal hyperplasia formation (more than 70% reduction), as well as improved vascular outward remodeling (increased vein diameter) and hemodynamic adaptation (lower wall shear stress approaching the preoperative level and less vorticity). Therefore, direct application of the NO releasing nanomatrix gel to the AVF anastomosis immediately following AVF creation may enhance AVF development, thereby providing long-term and durable vascular access for hemodialysis.

Rationale & Objective National vascular access guidelines recommend placement of arteriovenous fistulas (AVFs) over grafts (AVGs) in hemodialysis patients, but have not been comprehensively assessed in the elderly. We evaluated clinically relevant vascular access outcomes in elderly patients receiving an AVF or AVG after hemodialysis therapy initiation. Study Design Retrospective cohort study using national administrative data. Settings & Partcipants Claims data from the US Renal Data System of 9,458 US patients 67 years and older who initiated hemodialysis therapy from July 1, 2010, to June 30, 2011, with a catheter and received an AVF (n=7,433) or AVG (n=2,025) within the ensuing 6 months. Predictor Arteriovenous access subtype, AVF or AVG. Outcomes Successful use of vascular access, interventions to make vascular access functional, duration of catheter dependence before successful use of vascular access, frequency of interventions, and abandonment after successful use of vascular access. Analytical Approach Multivariable logistic regression analysis was used to compare the need for intervention before successful use of AVFs and AVGs, and negative bionomial regression was used to calculate the frequency of intervention after successful use of vascular access. Results Unsuccessful use of vascular access within 6 months of creation was higher for AVFs versus AVGs (51% vs 45%; adjusted HR, 1.86; 95% CI, 1.73-1.99). Interventions to make vascular access functional were greater in AVFs versus AVGs (42% vs 23%; OR, 2.66; 95% CI, 2.26-3.12). AVFs had a lower 1-year abandonment rate after successful use compared with AVGs (OR, 0.71; 95% CI, 0.62-0.83) and required one-fourth fewer interventions after successful use (relative risk, 0.75; 95% CI, 0.69-0.81). Patients receiving an AVF had substantially longer catheter dependence before successful use than those receiving an AVG (median time, 3 vs 1 month; P Limitations Residual confounding due to vascular access choice, restriction to an elderly population, and 1-year follow-up period. Conclusions In elderly hemodialysis patients initiating hemodialysis therapy with a catheter, the optimal vascular access selection depends on tradeoffs between shorter catheter dependence and less frequent interventions to make the vascular access (AVG) functional versus longer access patency and fewer interventions after successful use of the vascular access (AVF).

Background An arteriovenous fistula (AVF) is the recommended vascular access for hemodialysis (HD). Previous studies have not examined the resources and costs associated with creating and maintaining AVFs. Study Design Retrospective observational study. Setting & Participants Elderly US Medicare patients initiating hemodialysis therapy during 2010 to 2011. Predictor AVF primary and secondary patency and nonuse in the first year following AVF creation. Outcomes Annualized vascular access costs per patient per year. Results Among patients with only a catheter at HD therapy initiation, only 54% of AVFs were successfully used for HD, 10% were used but experienced secondary patency loss within 1 year of creation, and 83% experienced primary patency loss within 1 year of creation. Mean vascular access costs per patient per year in the 2.5 years after AVF creation were $7,871 for AVFs that maintained primary patency in year 1, $13,282 for AVFs that experienced primary patency loss in year 1, $17,808 for AVFs that experienced secondary patency loss in year 1, and $31,630 for AVFs that were not used. Similar patterns were seen among patients with a mature AVF at HD therapy initiation and patients with a catheter and maturing AVF at HD therapy initiation. Overall, in 2013, fee-for-service Medicare paid $2.8 billion for dialysis vascular access–related services, ∼12% of all end-stage renal disease payments. Limitations Lack of granularity with certain billing codes. Conclusions AVF failure in the first year after creation is common and results in substantially higher health care costs. Compared with patients whose AVFs maintained primary patency, vascular access costs were 2 to 3 times higher for patients whose AVFs experienced primary or secondary patency loss and 4 times higher for patients who never used their AVFs. There is a need to improve AVF outcomes and reduce costs after AVF creation.

Introduction: Arteriovenous fistulas (AVF) frequently fail to mature. Postoperative ultrasounds provide objective measurements to predict unassisted AVF use for hemodialysis (unassisted use) and guide interventions to salvage nonmaturing AVFs. The optimal ultrasound criteria to assess AVF maturation are uncertain. We analyzed data from a multicenter, randomized, controlled, clinical trial to compare 2 published ultrasound maturation criteria used to predict unassisted AVF use for hemodialysis. Methods: We retrospectively analyzed prospective data on 105 patients undergoing new AVF creation, who underwent standardized postoperative ultrasounds at 6 and 12 weeks to measure AVF diameter and blood flow. Unassisted AVF use was defined as successful cannulation for ≥90 days without requiring prior surgical or percutaneous interventions. Two ultrasound criteria were assessed: (i) National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative criteria: AVF outflow vein lumen diameter ≥6 mm and blood flow ≥600 mL/min; and (ii) University of Alabama at Birmingham (UAB) criteria: AVF outflow vein lumen diameter ≥4 mm and blood flow ≥500 mL/min. Performance characteristics were calculated for both criteria. Results: Compared to the NKF criteria, the UAB criteria had a higher sensitivity (89 vs.68%), but a lower specificity (42 vs. 70%) for unassisted AVF use. For radiocephalic AVFs, the UAB criteria had higher sensitivity (86 vs. 46%) and lower specificity (58 vs. 83%). For brachiocephalic AVFs, both UAB and NKF had high sensitivity (90 and 80%) but low specificity (21 and 53%), respectively. Conclusions: Using the UAB ultrasound criteria would minimize unnecessary early interventions in AVFs likely to mature without an intervention, but would delay interventions in AVFs that are unlikely to mature. The UAB criteria may be preferred in patients receiving a radiocephalic AVF.

Background: Acute kidney injury (AKI) is associated with increased morbidity and mortality. Mortality in end-stage renal disease (ESRD) patients is highest during the first year of dialysis. The impact of pre-ESRD AKI events on long-term outcomes in incident ESRD patients remains unknown. Methods: We evaluated a retrospective cohort of 47,341 incident hemodialysis patients from the United States Renal Data System with linked Medicare data for at least 2 years prior to hemodialysis initiation. We examined the impact of pre-ESRD AKI events in the 2-year pre-ESRD period on the type of vascular access used at hemodialysis initiation (central venous catheter (CVC) versus arteriovenous access), and 1-year all-cause mortality after initiating hemodialysis. Results: The mean age was 72 ± 11 years. Of the study cohort, 18% initiated hemodialysis with arteriovenous access, and 54% of patients had at least one pre-ESRD AKI event. One-year, all-cause mortality was 32%. Compared to 75% for patients without a pre-ESRD AKI event, 89% of patients with a pre-ESRD AKI event initiated hemodialysis with CVC than arteriovenous access (p < 0.001). A pre-ESRD AKI event was associated with lower adjusted odds of starting hemodialysis with an arteriovenous access (OR 0.47; 95% CI 0.44–0.50, p < 0.001), and higher adjusted odds of 1-year mortality (OR 1.36; 95% CI 1.30–1.42, p < 0.001). Conclusion: An AKI event prior to initiating hemodialysis independently increases the risk of CVC use and predicts 1-year mortality. Improving processes of care after AKI events may improve dialysis outcomes in patients who progress to ESRD.

To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles. Our WST-1 cell proliferation assay data indicate that nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved antiproliferative potency as compared with silybin toward both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O-Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can consistently inhibit cell proliferation in three prostate cancer cell models with all IC50 values lower than 8 μM. Our flow cytometry-based assays also demonstrate that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the G0/G1 phase and activates PC-3 cell apoptosis.

Patients in the United States frequently initiate hemodialysis with a central venous catheter (CVC) and subsequently undergo placement of a new arteriovenous fistula (AVF) or arteriovenous graft (AVG). Little is known about the clinical and economic effects of initial vascular access choice. We identified 479 patients starting hemodialysis with a CVC at a large medical center (during 2004–2012) who subsequently had an AVF (n=295) or AVG (n=105) placed or no arteriovenous access (CVC group, n=71). Compared with patients receiving an AVG, those receiving an AVF had more frequent surgical access procedures per year (1.01 [95% confidence interval, 0.95 to 1.08] versus 0.62 [95% confidence interval, 0.55 to 0.70]; P

Background: Patients with advanced chronic kidney disease frequently undergo arteriovenous fistula creation prior to reaching end-stage renal disease (ESRD), but some initiate hemodialysis with a central vein catheter, if their fistula is not yet usable. The clinical consequences of the delay in fistula use have not been quantified in such patients. We compared patients with pre-ESRD fistula surgery who initiated dialysis with a catheter versus a fistula in terms of the frequency of post-dialysis vascular access procedures and complications and their economic impact. Methods: We identified 205 patients with predialysis fistula creation from 2006 to 2012 at a large dialysis center who started hemodialysis within the ensuing 2 years. Of these, 91 (44%) initiated dialysis with a catheter and 114 (56%) with a fistula. We compared these 2 groups in terms of their annual frequency of percutaneous vascular access procedures, surgical access procedures, total access procedures, hospitalizations due to catheter-related bacteremia, and overall cost of vascular access management. Results: The 2 groups were similar in demographics, comorbidities, and fistula type. As compared to patients initiating dialysis with a fistula, those initiating with a catheter had a significantly greater annual frequency of percutaneous access procedures (1.29 [1.19–1.40] vs. 0.75 [0.68–0.82]), surgical access procedures (0.69 [0.61–0.76] vs. 0.59 [0.53–0.66]), total access procedures (1.98 [1.86–2.11] vs. 1.34 [1.26–1.44]), and hospitalizations due to catheter-related bacteremia (0.09 [0.07–0.12] vs. 0.02 [0.01–0.03]). Patients initiating dialysis with a catheter incurred a median overall annual cost of access management that was USD 2,669 higher (USD 6,372 [3,121–12,242) vs. USD 3,703 [1,867–6,953], p = 0.0001). Conclusion: Among patients with predialysis fistula creation, those initiating dialysis with a catheter versus a fistula had substantially more frequent percutaneous, surgical, and total vascular access procedures, as well as hospitalizations due to catheter-related bacteremia. The annual cost of access management was substantially higher in those initiating dialysis with a catheter.

Vascular access is the lifeline for patients on hemodialysis. Arteriovenous fistulas (AVFs) are the preferred vascular access, but AVF maturation failure remains a significant clinical problem. Currently, there are no effective therapies available to prevent or treat AVF maturation failure. AVF maturation failure frequently results from venous stenosis at the AVF anastomosis, which is secondary to poor outward vascular remodeling and excessive venous intimal hyperplasia that narrows the AVF lumen. Arteriovenous grafts (AVGs) are the next preferred vascular access when an AVF creation is not possible. AVG failure is primarily the result of venous stenosis at the vein-graft anastomosis, which originates from intimal hyperplasia development. Although there has been advancement in our knowledge of the pathophysiology of AVF maturation and AVG failure, this has not translated into effective therapies for these two important clinical problems. Further work will be required to dissect out the mechanisms of AVF maturation failure and AVG failure to develop more specific therapies. This review highlights the major recent advancements in AVF and AVG biology, reviews major clinical trials, and discusses new areas for future research.

Arteriovenous fistula (AVF) maturation failure remains a major cause of morbidity and mortality in hemodialysis patients. The two major etiologies of AVF maturation failure are early neointimal hyperplasia development and persistent inadequate outward remodeling. Although hemodynamic changes following AVF creation may impact AVF remodeling and contribute to neointimal hyperplasia development and impaired outward remodeling, detailed AVF hemodynamics are not yet fully known. Since murine AVF models are valuable tools for investigating the pathophysiology of AVF maturation failure, there is a need for a new approach that allows the hemodynamic characterization of murine AVF at high resolutions.This methods paper presents a magnetic resonance imaging (MRI)-based computational fluid dynamic (CFD) method that we developed to rigorously quantify the evolving hemodynamic environment in murine AVF. The lumen geometry of the entire murine AVF was reconstructed from high resolution, non-contrast 2D T2-weighted fast spin echo MRI sequence, and the flow rates of the AVF inflow and outflow were extracted from a gradient echo velocity mapping sequence. Using these MRI-obtained lumen geometry and inflow information, CFD modeling was performed and used to calculate blood flow velocity and hemodynamic factors at high resolutions (on the order of 0.5 μm spatially and 0.1 ms temporally) throughout the entire AVF lumen. We investigated both the wall properties (including wall shear stress (WSS), wall shear stress spatial gradient, and oscillatory shear index (OSI)) and the volumetric properties (including vorticity, helicity, and Q-criterion).Our results demonstrate increases in AVF flow velocity, WSS, spatial WSS gradient, and OSI within 3 weeks post-AVF creation when compared to pre-surgery. We also observed post-operative increases in flow disturbances and vortices, as indicated by increased vorticity, helicity, and Q-criterion.This novel protocol will enable us to undertake future mechanistic studies to delineate the relationship between hemodynamics and AVF development and characterize biological mechanisms that regulate local hemodynamic factors in transgenic murine AVF models.

Background About half of arteriovenous fistulas (AVFs) require one or more interventions before successful dialysis use, a process called assisted maturation. Previous research suggested that AVF abandonment and interventions to maintain patency after maturation may be more frequent with assisted maturation versus unassisted maturation. Methods Using the US Renal Data System, we retrospectively compared patients with assisted versus unassisted AVF maturation for postmaturation AVF outcomes, including functional primary patency loss (requiring intervention after achieving AVF maturation), AVF abandonment, and frequency of interventions. Results We included 7301 patients ≥67 years who initiated hemodialysis from July 2010 to June 2012 with a catheter and no prior AVF; all had an AVF created within 6 months of starting hemodialysis and used for dialysis (matured) within 6 months of creation, with 2-year postmaturation follow-up. AVFs matured without prior intervention for 56% of the patients. Assisted AVF maturation with one, two, three, or four or more prematuration interventions occurred in 23%, 12%, 5%, and 4% of patients, respectively. Patients with prematuration interventions had significantly increased risk of functional primary patency loss compared with patients who had unassisted AVF maturation, and the risk increased with the number of interventions. Although the likelihood of AVF abandonment was not higher among patients with up to three prematuration interventions compared with patients with unassisted AVF maturation, it was significantly higher among those with four or more interventions. Conclusions For this cohort of patients undergoing assisted AVF maturation, we observed a positive association between the number of prematuration AVF interventions and the likelihood of functional primary patency loss and frequency of postmaturation interventions.

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes. ispartof: pages:1053-1068 ispartof: Kidney Int vol:94 issue:6 pages:1053-1068 ispartof: location:United States status: published

Background and objectives Few studies have evaluated vascular access use after transition from peritoneal dialysis to hemodialysis. Our study characterizes vascular access use after switch to hemodialysis and its effect on patient mortality and evaluates whether a peritonitis event preceding the switch was associated with the timing of permanent vascular access placement and use. Design, setting, participants, & measurements The US Renal Data System data were used to evaluate the establishment of a permanent vascular access in 1165 incident Medicare–insured adult patients on dialysis who initiated peritoneal dialysis between July 1, 2010 and June 30, 2011 and switched to hemodialysis within 1 year. Results The proportions of patients using a hemodialysis catheter were 85% (744 of 879), 76% (513 of 671), and 51% (298 of 582) at 30, 90, and 180 days, respectively, after the switch from peritoneal dialysis to hemodialysis. Patients who switched from peritoneal dialysis to hemodialysis with a previous peritonitis episode were more likely to dialyze with a catheter at 30 days (90% [379 of 421] versus 80% [365 of 458]; P =0.03), 90 days (82% [275 of 334] versus 71% [238 of 337]; P =0.03), and 180 days (57% [166 of 289] versus 45% [132 of 293]; P =0.04) after the switch and less likely to dialyze with an arteriovenous fistula at 30 days (8% [32 of 421] versus 16% [73 of 458]; P =0.01), 90 days (13% [42 of 334] versus 23% [76 of 337]; P =0.03), and 180 days (31% [91 of 289] versus 43% [126 of 293]; P =0.04). Patients using a permanent vascular access 180 days after switching from peritoneal dialysis to hemodialysis had better adjusted survival during the ensuing year than those using a catheter (hazard ratio, 0.66; 95% confidence interval, 0.44 to 1.00; P =0.05). Conclusions Among patients who switch from peritoneal dialysis to hemodialysis, prior peritonitis is associated with a higher rate of persistent hemodialysis catheter use, which in turn, is associated with lower patient survival. Studies addressing vascular access planning and implementation are needed in this group of patients.

Eight 3-O-alkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin through two synthetic approaches. A one-pot reaction, starting with aerobic oxidation of silibinin followed by direct alkylation of the phenolic hydroxyl group in the subsequent 2,3-dehydrosilibinin, furnishes the desired derivatives in 11–16% yields. The three-step procedure employing benzyl ether to protect 7-OH in silibinin generates the desired derivatives in 30–46% overall yields. The antiproliferative activity of the 2,3-dehydrosilibinin derivatives against both androgen-sensitive and androgen-insensitive prostate cancer cells have been assessed using a WST-1 cell proliferation assay. All derivatives exhibited greater antiproliferative potency than silibinin, with 2,3-dehydrosilibinins each possessing a three- to five-carbon linear alkyl group to 3-OH (IC50 values in a range of 1.71 to 3.06 μM against PC-3 and LNCaP cells) as the optimal derivatives. The optimal potency was reached with three- to five-carbon alkyl groups. Our findings suggest that 3-O-propyl-2,3-dehydrosilibinin effectively inhibits the growth of PC-3 prostate cancer cells by arresting cell cycle in the G0/G1 phase, but not by activating PC-3 cell apoptosis.

Optimizing vascular access outcomes remains a major challenge, despite the accumulation of consensus guidelines during the past 20 years. The initial Kidney Disease Outcomes Quality Initiative guidelines published in 1997 ([1][1]) and updated in 2001 ([2][2]) and 2006 ([3][3]) as well as the “

Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms. Whether different ICAM-1 N-glycoforms are expressed in vivo during disease is unknown. In this study, using the proximity ligation assay, we assessed the relative formation of high mannose, hybrid and complex α-2,6-sialyated N-glycoforms of ICAM-1 in human and mouse models of atherosclerosis, as well as in arteriovenous fistulas (AVF) of patients on hemodialysis. Our data demonstrates that ICAM-1 harboring HM or hybrid epitopes as well as ICAM-1 bearing α-2,6-sialylated epitopes are present in human and mouse atherosclerotic lesions. Further, HM-ICAM-1 positively associated with increased macrophage burden in lesions as assessed by CD68 staining, whereas α-2,6-sialylated ICAM-1 did not. Finally, both HM and α-2,6-sialylated ICAM-1 N-glycoforms were present in hemodialysis patients who had AVF maturation failure compared to successful AVF maturation. Collectively, these data provide evidence that HM- ICAM-1 N-glycoforms are present in vivo, and at levels similar to complex α-2,6-sialylated ICAM-1 underscoring the need to better understand their roles in modulating vascular inflammation.

BACKGROUND AND OBJECTIVES: Postoperative ultrasound is commonly used to assess arteriovenous fistula (AVF) maturation for hemodialysis, but its utility for predicting unassisted AVF maturation or primary AVF patency for hemodialysis has not been well defined. This study assessed the predictive value of postoperative AVF ultrasound measurements for these clinical AVF outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We queried a prospective vascular access database to identify 246 patients on catheter-dependent hemodialysis who underwent AVF creation between 2010 and 2016 and obtained a postoperative ultrasound within 90 days. Multivariable logistic regression was used to evaluate the association of clinical characteristics and postoperative ultrasound measurements with unassisted AVF maturation. A receiver operating characteristic curve estimated the predictive value of these factors for unassisted AVF maturation. Finally, multivariable survival analysis was used to identify factors associated with primary AVF patency in patients with unassisted AVF maturation. RESULTS: Unassisted AVF maturation occurred in 121 out of 246 patients (49%), assisted maturation in 55 patients (22%), and failure to mature in 70 patients (28%). Using multivariable logistic regression, unassisted AVF maturation was associated with AVF blood flow (odds ratio [OR], 1.30; 95% confidence interval [95% CI], 1.18 to 1.45 per 100 ml/min increase; P

Objective Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. Methods PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. Results The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use. Conclusions Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.

Early fistula failure (EFF) is a significant clinical problem causing lower rates of arteriovenous fistulae (AVFs) use in patients with ESRD on hemodialysis. The 2 main factors amenable to treatment and widely accepted to cause EFF are stenosis anywhere in the AVF circuit and/or presence of accessory vein (av). The role of stenotic lesions in causing EFF and their treatment options are relatively better defined with clear guidelines. On the other hand, assessing the significance of an av in causing EFF and the indications for its treatment seem to lack scientific recommendations based on robust clinical data. In this article, we review the pathophysiology of EFF as pertains to the presence of av's. Current recommendations for obliteration of av, the available techniques and the evidence to support current clinical practice are discussed. The possible cons of av obliteration are highlighted, while newer concepts and the need for future clinical trials are addressed.

This paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access’ evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1—patent arteriovenous access, stage 2—physiologically mature arteriovenous access, and stage 3—clinically functional arteriovenous access. Once the requirements of a stage 3—clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.

Background Half of surgically created arteriovenous fistulas (AVFs) require additional intervention to effectively support hemodialysis. Postoperative care and complications may affect clinical maturation. Study Design Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study. Setting & Participants 491 patients with single-stage AVFs who had neither thrombosis nor AVF intervention before a 6-week postoperative ultrasonographic examination and who required maintenance hemodialysis. Predictors Postoperative care processes and complications. Outcomes Attempted cannulation, successful cannulation, and unassisted and overall clinical maturation as defined by the HFM Study criteria. Results AVF cannulation was attempted in 443 of 491 (90.2%) participants and was eventually successful in 430 of these 443 (97.1%) participants. 263 of these 430 (61.2%) reached unassisted and 118 (27.4%) reached assisted AVF maturation (overall maturation, 381/430 [88.6%]). Attempted cannulation was less likely in patients of surgeons with policies for routine 2-week versus later-than-2-week first postoperative visits (OR, 0.21; 95% CI, 0.06-0.70), routine second postoperative follow-up visits (OR, 0.39; 95% CI, 0.15-0.97), and a routine clinical postoperative ultrasound (OR, 0.28; 95% CI, 0.14-0.55). Attempted cannulation was also less likely among patients undergoing procedures to assist maturation (OR, 0.51; 95% CI, 0.27-0.98). Unassisted maturation was more likely for patients treated in facilities with access coordinators (OR, 1.91; 95% CI, 1.17-3.12), but less likely after precannulation nonstudy ultrasounds (OR per ultrasound, 0.42 [95% CI, 0.26-0.68]) and initial unsuccessful cannulation attempts (OR per each additional attempt, 0.90 [95% CI, 0.83-0.98]). Overall maturation was less likely with infiltration before successful cannulation (OR, 0.44; 95% CI, 0.22-0.89). Among participants receiving maintenance hemodialysis before AVF surgery, unassisted and overall maturation were less likely with longer intervals from surgery to initial cannulation (ORs for each additional month of 0.81 [95% CI, 0.76-0.88] and 0.93 [95% CI, 0.89-0.98], respectively) and from initial to successful cannulation (ORs for each additional week of 0.87 [95% CI, 0.81-0.94] and 0.88 [95% CI, 0.83-0.94], respectively). Limitations Surgeons' management policies were assessed only by questionnaire at study onset. Most participants received upper-arm AVFs, planned 2-stage AVFs were excluded, and maturation time windows were imposed. Some care processes may have been missed and the observational design limits causal attribution. Conclusions Multiple processes of care and complications are associated with AVF maturation outcomes.

Head and neck cancer is one of the leading malignancies worldwide. Due to the lack of symptoms in the early stage of the disease, about two thirds of patients present with locally advanced disease at the time of diagnosis. Even with significantly improved survival rates over the past two decades due to advanced imaging and treatment modalities, locoregional recurrence rates in patients with advanced disease ranges from 16% to 35%. Alternative therapeutic targets are being developed to improve survival outcomes. MicroRNAs (miRNA or miRs) are a family of small non-coding RNA species that have been demonstrated to regulate all cellular, physiological and developmental processes. Recently, there has been an exponential increase in the number of studies suggesting that miRNA is involved in regulating tumor metastasis, chemoresistance, radioresistance and survival outcomes. MiRNA candidates have been identified as potential prognostic biomarkers to diagnose cancer stages and progression, as well as to monitor follow-up treatment. In this review, we will discuss the miRNA profile in each stage of head and neck patients' therapy, with an emphasis on its application to clinical outcome prognosis.

Background Arteriovenous fistula (AVF) maturation failure remains a major cause of morbidity and mortality in hemodialysis patients. The two major etiologies of AVF maturation failure are early neointimal hyperplasia development and persistent inadequate outward remodeling. Although hemodynamic changes following AVF creation may impact AVF remodeling and contribute to neointimal hyperplasia development and impaired outward remodeling, detailed AVF hemodynamics are not yet fully known. Since murine AVF models are valuable tools for investigating the pathophysiology of AVF maturation failure, there is a need for a new approach that allows the hemodynamic characterization of murine AVF at high resolutions. Methods This methods paper presents a magnetic resonance imaging (MRI)-based computational fluid dynamic (CFD) method that we developed to rigorously quantify the evolving hemodynamic environment in murine AVF. The lumen geometry of the entire murine AVF was reconstructed from high resolution, non-contrast 2D T2-weighted fast spin echo MRI sequence, and the flow rates of the AVF inflow and outflow were extracted from a gradient echo velocity mapping sequence. Using these MRI-obtained lumen geometry and inflow information, CFD modeling was performed and used to calculate blood flow velocity and hemodynamic factors at high resolutions (on the order of 0.5 μm spatially and 0.1 ms temporally) throughout the entire AVF lumen. We investigated both the wall properties (including wall shear stress (WSS), wall shear stress spatial gradient, and oscillatory shear index (OSI)) and the volumetric properties (including vorticity, helicity, and Q-criterion). Results Our results demonstrate increases in AVF flow velocity, WSS, spatial WSS gradient, and OSI within 3 weeks post-AVF creation when compared to pre-surgery. We also observed post-operative increases in flow disturbances and vortices, as indicated by increased vorticity, helicity, and Q-criterion. Conclusions This novel protocol will enable us to undertake future mechanistic studies to delineate the relationship between hemodynamics and AVF development and characterize biological mechanisms that regulate local hemodynamic factors in transgenic murine AVF models. Electronic supplementary material The online version of this article (doi:10.1186/s12976-017-0053-x) contains supplementary material, which is available to authorized users.

Background and objectives The optimal type of initial permanent access for hemodialysis among the elderly is controversial. Duration of central venous catheter dependence, patient comorbidities, and life expectancy are important considerations in whether to place an arteriovenous fistula or graft. We used an observational study design to compare clinical outcomes in elderly patients who initiated hemodialysis with a central venous catheter and subsequently had an arteriovenous fistula or graft placed. Design, setting, participants, & measurements We identified 9458 United States patients ages ≥67 years old who initiated hemodialysis from July 1, 2010 to June 30, 2011 with a central venous catheter and no secondary vascular access and then received an arteriovenous fistula (n=7433) or graft (n=2025) within 6 months. We evaluated key clinical outcomes during the 6 months after vascular access placement coincident with high rates of catheter use and used a matched propensity score analysis to examine patient survival. Results Central venous catheter dependence was greater in every month during the 6-month period after arteriovenous fistula versus graft placement (P Conclusions Despite extended central venous catheter dependence, elderly patients initiating hemodialysis with a central venous catheter who underwent arteriovenous fistula placement within 6 months had fewer hospitalizations due to infections and a lower likelihood of death than those receiving an arteriovenous graft.

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.

The vascular access is the lifeline for the hemodialysis patient. In the United States, the Fistula First Breakthrough Initiative (FFBI) has been influential in improving use of arteriovenous fistulas (AVF) in prevalent hemodialysis patients. Currently, prevalent AVF rates are near the goal of 66% set forth by the original FFBI. However, central venous catheter (CVC) rates remain very high in the United States in patients initiating hemodialysis, nearly exceeding 80%. A new direction of the of the FFBI has focused on strategies to reduce CVC use, and subsequently the FFBI has now been renamed the “Fistula First-Catheter Last Initiative”. However, an AVF may not be the best vascular access in all hemodialysis patients, and arteriovenous grafts (AVG) and central venous catheters (CVC) may be appropriate and the best access for a subset of hemodialysis patients. Unfortunately, there still remains very little emphasis within vascular access initiatives and guidelines directed towards evaluation of the individual patient context, specifically patients with poor long-term prognoses and short life expectancies, patients with multiple comorbidities, patients who are more likely to die than reach end stage renal disease (ESRD), and patients of elderly age with impaired physical and cognitive function. Given the complexity of medical and social issues in advanced CKD and ESRD patients, planning, selection, and placement of the most appropriate vascular access are ideally managed within a multidisciplinary setting and requires consideration of several factors including national vascular access guidelines. Thus, the evolution of the FFBI should underscore the need for multidisciplinary health teams with a major emphasis placed on “the right access for the right patient” and improving the patient’s overall quality of life.