Acute kidney injury results in long-term alterations of kidney lymphatics in mice.

The long-term effects of a single episode of acute kidney injury (AKI) induced by bilateral ischemia-reperfusion injury (BIRI) on kidney lymphatic dynamics are not known. The purpose of this study was to determine if alterations in kidney lymphatics are sustained in the long term and how they relate to inflammation and injury. Mice underwent BIRI as a model of AKI and were followed up to 9 mo. Although kidney function markers normalized following initial injury, histological analysis revealed sustained tissue damage and inflammation for up to 9 mo. Transcriptional analysis showed both acute and late-stage lymphangiogenesis, supported by increased expression of lymphatic markers, with unique signatures at each phase. Expression of Ccl21a was distinctly upregulated during late-stage lymphangiogenesis. Three-dimensional tissue cytometry confirmed increased lymphatic vessel abundance, particularly in the renal cortex, at early and late timepoints postinjury. In addition, the study identified the formation of tertiary lymphoid structures composed of CCR7+ lymphocytes and observed changes in immune cell composition over time, suggesting a complex and dynamic response to AKI involving tissue remodeling and immune cell involvement. This study provides new insights into the role of lymphatics in the progression of AKI to chronic kidney disease.NEW & NOTEWORTHY Here, we perform the first, comprehensive study of long-term lymphatic dynamics following a single acute kidney injury (AKI) event. Using improved three-dimensional image analysis and an expanded panel of transcriptional markers, we identify multiple stages of lymphatic responses with distinct transcriptional signatures, associations with the immune microenvironment, and collagen deposition. This research advances kidney lymphatic biology, emphasizing the significance of longitudinal studies in understanding AKI and the transition to chronic kidney disease.

Effects of a More Selective Arteriovenous Fistula Strategy on Vascular Access Outcomes.

SIGNIFICANCE STATEMENT: The optimal choice of vascular access for patients undergoing hemodialysis-arteriovenous fistula (AVF) or arteriovenous graft (AVG)-remains controversial. In a pragmatic observational study of 692 patients, the authors found that among patients who initiated hemodialysis with a central vein catheter (CVC), a strategy that maximized AVF placement resulted in a higher frequency of access procedures and greater access management costs for patients who initially received an AVF than an AVG. A more selective policy that avoided AVF placement if an AVF was predicted to be at high risk of failure resulted in a lower frequency of access procedures and access costs in patients receiving an AVF versus an AVG. These findings suggest that clinicians should be more selective in placing AVFs because this approach improves vascular access outcomes. BACKGROUND: The optimal choice of initial vascular access-arteriovenous fistula (AVF) or graft (AVG)-remains controversial, particularly in patients initiating hemodialysis with a central venous catheter (CVC). METHODS: In a pragmatic observational study of patients who initiated hemodialysis with a CVC and subsequently received an AVF or AVG, we compared a less selective vascular access strategy of maximizing AVF creation (period 1; 408 patients in 2004 through 2012) with a more selective policy of avoiding AVF creation if failure was likely (period 2; 284 patients in 2013 through 2019). Prespecified end points included frequency of vascular access procedures, access management costs, and duration of catheter dependence. We also compared access outcomes in all patients with an initial AVF or AVG in the two periods. RESULTS: An initial AVG placement was significantly more common in period 2 (41%) versus period 1 (28%). Frequency of all access procedures per 100 patient-years was significantly higher in patients with an initial AVF than an AVG in period 1 and lower in period 2. Median annual access management costs were significantly higher among patients with AVF ($10,642) versus patients with AVG ($6810) in period 1 but significantly lower in period 2 ($5481 versus $8253, respectively). Years of catheter dependence per 100 patient-years was three-fold higher in patients with AVF versus patients with AVG in period 1 (23.3 versus 8.1, respectively), but only 30% higher in period 2 (20.8 versus 16.0, respectively). When all patients were aggregated, the median annual access management cost was significantly lower in period 2 ($6757) than in period 1 ($9781). CONCLUSIONS: A more selective approach to AVF placement reduces frequency of vascular access procedures and cost of access management.

Study protocol of a randomized controlled trial of fistula vs. graft arteriovenous vascular access in older adults with end-stage kidney disease on hemodialysis: the AV access trial.

BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).

Study protocol for Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) : A multi-center, multinational validation study to assess the accuracy and feasibility of measuring vascular access function in clinical practice.

BACKGROUND: A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. METHODS: VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. DISCUSSION: Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Early Predictors of Arteriovenous Fistula Maturation: A Novel Perspective on an Enduring Problem.

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.

KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update.

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.

A Novel Model of Balloon Angioplasty Injury in Rat Arteriovenous Fistula.

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.

Vasoreactivity of the Murine External Jugular Vein and Carotid Artery.

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.

Research Themes and Trends in Ten Top-Ranked Nephrology Journals: A Text Mining Analysis.

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.

Identifying critically important vascular access outcomes for trials in haemodialysis: an international survey with patients, caregivers and health professionals.

BACKGROUND: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes. METHOD: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically. RESULTS: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle. CONCLUSIONS: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD.

Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study.

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.

Arteriovenous conduits for hemodialysis: how to better modulate the pathophysiological vascular response to optimize vascular access durability.

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.

A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis.

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.

Gender Disparities in Vascular Access Surgical Outcomes in Elderly Hemodialysis Patients.

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.

Clinical Outcomes and Economic Impact of Starting Hemodialysis with a Catheter after Predialysis Arteriovenous Fistula Creation.

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.

Correction to: High resolution hemodynamic profiling of murine arteriovenous fistula using magnetic resonance imaging and computational fluid dynamics.

After publication of the original article.

Tradeoffs in Vascular Access Selection in Elderly Patients Initiating Hemodialysis With a Catheter.

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<0.001). 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).

Medicare Costs Associated With Arteriovenous Fistulas Among US Hemodialysis Patients.

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.

Vascular Access Outcomes Reported in Maintenance Hemodialysis Trials: A Systematic Review.

BACKGROUND: Many randomized controlled trials have been performed with the goal of improving outcomes related to hemodialysis vascular access. If the reported outcomes are relevant and measured consistently to allow comparison of interventions across trials, such trials can inform decision making. This study aimed to assess the scope and consistency of vascular access outcomes reported in contemporary hemodialysis trials. STUDY DESIGN: Systematic review. SETTING & POPULATION: Adults requiring maintenance hemodialysis. SELECTION CRITERIA: All randomized controlled trials and trial protocols reporting vascular access outcomes identified from ClinicalTrials.gov, Embase, MEDLINE, and the Cochrane Kidney and Transplant Specialized Register from January 2011 to June 2016. INTERVENTIONS: Any hemodialysis-related intervention. OUTCOMES: The frequency and characteristics of vascular access outcome measures were analyzed and classified. RESULTS: From 168 relevant trials, 1,426 access-related outcome measures were extracted and classified into 23 different outcomes. The 3 most common outcomes were function (136 [81%] trials), infection (63 [38%]), and maturation (31 [18%]). Function was measured in 489 different ways, but most frequently reported as "mean access blood flow (mL/min)" (37 [27%] trials) and "number of thromboses" (30 [22%]). Infection was assessed in 136 different ways, with "number of access-related infections" being the most common measure. Maturation was assessed in 44 different ways at 15 different time points and most commonly characterized by vein diameter and blood flow. Patient-reported outcomes, including pain (19 [11%]) and quality of life (5 [3%]), were reported infrequently. Only a minority of trials used previously standardized outcome definitions. LIMITATIONS: Restricted sampling frame for feasibility and focus on contemporary trials. CONCLUSIONS: The reporting of access outcomes in hemodialysis trials is very heterogeneous, with limited patient-reported outcomes and infrequent use of standardized outcome measures. Efforts to standardize outcome reporting for vascular access are critical to optimizing the comparability, reliability, and value of trial evidence to improve outcomes for patients requiring hemodialysis.