The molecular mechanisms of hemodialysis vascular access failure.
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ABSTRACT:
SUBMITTER: Brahmbhatt A
PROVIDER: S-EPMC4734360 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
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The molecular mechanisms of hemodialysis vascular access failure.
Brahmbhatt Akshaar A Remuzzi Andrea A Franzoni Marco M Misra Sanjay S
Kidney international 20160201 2
The arteriovenous fistula has been used for more than 50 years to provide vascular access for patients undergoing hemodialysis. More than 1.5 million patients worldwide have end stage renal disease and this population will continue to grow. The arteriovenous fistula is the preferred vascular access for patients, but its patency rate at 1 year is only 60%. The majority of arteriovenous fistulas fail because of intimal hyperplasia. In recent years, there have been many studies investigating the mo ...[more]
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Project description:INTRODUCTION:Central venous catheters (CVC) increase risks associated with hemodialysis (HD), but may be necessary until an arteriovenous fistula (AVF) or graft (AVG) is achieved. The impact of vascular imaging on achievement of working AVF and AVG has not been firmly established. METHODS:Retrospective cohort of patients initiating HD with CVC in 2010-2011, classified by exposure to venography or Doppler vein mapping, and followed through December 31, 2012. Standard and time-dependent Cox models were used to determine hazard ratios (HRs) of death, working AVF, and any AVF or AVG. Logistic regression was used to assess the association of preoperative imaging with successful AVF or AVG among 18,883 individuals who had surgery. Models were adjusted for clinical and demographic factors. FINDINGS:Among 33,918 patients followed for a median of 404 days, 39.1% had imaging and 55.7% had surgery. Working AVF or AVG were achieved in 40.6%; 46.2% died. Compared to nonimaged patients, imaged patients were more likely to achieve working AVF (HR?=?1.45 [95% confidence interval [CI] 1.36, 1.55], P?<?0.001]), any AVF or AVG (HR?=?1.63 [1.58, 1.69], P?>?0.001), and less likely to die (HR?=?0.88 [0.83-0.94], P?<?0.001). Among patients who had surgery, the odds ratio for any successful AVF or AVG was 1.09 (1.02-1.16, P?=?0.008). DISCUSSION:Fewer than half of patients who initiated HD with a CVC had vascular imaging. Imaged patients were more likely to have vascular surgery and had increased achievement of working AV fistulas and grafts. Outcomes of surgery were similar in patients who did and did not have imaging.
| S-EPMC5438785 | biostudies-literature
Project description:Most arteriovenous grafts fail due to irreversible thrombosis, and most clotted grafts have an underlying stenotic lesion. These observations raise the plausible hypothesis that early detection of graft stenosis with preemptive angioplasty will reduce the likelihood of graft thrombosis. A number of noninvasive methods can be used to detect hemodynamically significant graft stenosis with a high positive predictive value. These tests include clinical monitoring, as well as surveillance by static dialysis venous pressures, flow monitoring, or duplex ultrasound. However, these surveillance tests have a much lower positive predictive value for graft thrombosis in the absence of preemptive angioplasty. In other words, none of the currently available surveillance tests can reliably distinguish between stenosed grafts destined to clot, and those that will remain patent without intervention. As a consequence, any program of graft surveillance necessarily results in a substantial proportion of unnecessary angioplasties. Moreover, a substantial proportion of grafts thrombose despite a normal antecedent surveillance test. Numerous observational studies have found an impressive reduction of graft thrombosis after implementation of a stenosis surveillance program. In contrast, 5 of 6 randomized clinical trials failed to show a reduction of graft thrombosis in patients undergoing graft surveillance, as compared with those receiving only clinical monitoring. The lack of benefit of surveillance is largely attributable to the rapid recurrence of stenosis after angioplasty. Thus, routine surveillance for graft stenosis, with preemptive angioplasty, cannot be recommended for reduction of graft thrombosis. Future research should be directed at pharmacologic interventions to prevent graft stenosis.
| S-EPMC4017945 | biostudies-literature
Project description:Frequent hemodialysis requires using the vascular access more often than with conventional hemodialysis, but whether this increases the risk for access-related complications is unknown. In two separate trials, we randomly assigned 245 patients to receive in-center daily hemodialysis (6 days per week) or conventional hemodialysis (3 days per week) and 87 patients to receive home nocturnal hemodialysis (6 nights per week) or conventional hemodialysis, for 12 months. The primary vascular access outcome was time to first access event (repair, loss, or access-related hospitalization). Secondary outcomes were time to all repairs and time to all losses. In the Daily Trial, 77 (31%) of 245 patients had a primary outcome event: 33 repairs and 15 losses in the daily group and 17 repairs, 11 losses, and 1 hospitalization in the conventional group. Overall, the risk for a first access event was 76% higher with daily hemodialysis than with conventional hemodialysis (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.11-2.79; P=0.017); among the 198 patients with an arteriovenous (AV) access at randomization, the risk was 90% higher with daily hemodialysis (HR, 1.90; 95% CI, 1.11-3.25; P=0.02). Daily hemodialysis patients had significantly more total AV access repairs than conventional hemodialysis patients (P=0.011), with 55% of all repairs involving thrombectomy or surgical revision. Losses of AV access did not differ between groups (P=0.58). We observed similar trends in the Nocturnal Trial, although the results were not statistically significant. In conclusion, frequent hemodialysis increases the risk of vascular access complications. The nature of the AV access repairs suggests that this risk likely results from increased hemodialysis frequency rather than heightened surveillance.
| S-EPMC3582201 | biostudies-literature
Project description:Background and objectivesMedicare reimbursement policy encourages frequent provider visits to patients with ESRD undergoing hemodialysis. This study sought to determine whether more frequent face-to-face provider (physician and advanced practitioner) visits lead to more procedures and therapeutic interventions aimed at preserving arteriovenous fistulas and grafts, improved vascular access outcomes, and fewer related hospitalizations.Design, setting, participants, & measurementsMultivariable regression was used to evaluate the association between provider (physician and advanced practitioner) visit frequency and interventions aimed at preserving vascular access, vascular access survival, hospitalization for vascular access infection, and outpatient antibiotic use in a cohort of 63,488 Medicare beneficiaries receiving hemodialysis in the United States. Medicare claims were used to identify the type of vascular access used, access-related events, and vascular access failure.ResultsOne additional provider (physician and advanced practitioner) visit per month was associated with a 13% higher odds of receiving an intervention to preserve vascular access (95% confidence interval [95% CI], 12% to 14%) but was not associated with vascular access survival (hazard ratio, 1.01; 95% CI, 0.99 to 1.03). One additional provider visit was associated with a 9% (95% CI, 5% to 14%) lower odds of hospitalization for vascular access infection and a corresponding 9% (95% CI, 5% to 14%) higher odds of outpatient intravenous antibiotic administration. However, the associated changes in absolute probabilities of hospitalization and antibiotic administration were small.ConclusionsMore frequent face-to-face provider (physician and advanced practitioner) visits were associated with more procedures and therapeutic interventions aimed at preserving vascular accesses, but not with prolonged vascular access survival and only a small decrease in hospitalization for vascular access.
| S-EPMC4317740 | biostudies-literature
Project description:BackgroundTo describe vascular access (VA)-related decision-making from the patient perspective, in patients who have already chosen hemodialysis as their renal replacement modality, and identify areas where physicians can improve this experience.MethodsIn-person, semi-structured interviews with 15 patients with end-stage kidney disease were systematically analyzed by two independent researchers using thematic analysis. Interviews were conducted until systematic analysis revealed no new themes.ResultsPatients had mean age 57 (range 22-85), with seven males and diverse racial/ethnic/marital status. All (15/15) patients viewed VA as "intertwined and interrelated" with dialysis, prioritized the dialysis, described the VA merely as the "hookup" to life-preserving dialysis and gave it minimal consideration. Three themes were identified: consolidation of dialysis and VA, reliance on supportive advisors and communication with physicians. Although 14/15 patients described processes common to medical decision-making, including information seeking, learning from the experiences of others, and weighing risks and benefits, they did not apply these processes specifically to VA. While all participants took ownership of the VA decision, they lacked clear understanding about the different types of VA and their consequences. Most patients (14/15) depended on family and friends for reinforcement, motivation and advice. Patients all described physician characteristics they associated with trustworthiness, the most common being listening and explaining, demonstrating empathy and making an effort to meet the patient's individual needs. Perceived arrogance, unavailability and lack of expertise represented untrustworthiness. The majority (14/15) accepted VA recommendations from physicians they found trustworthy and authoritative.ConclusionsThe study participants were minimally engaged in VA decision-making. Educational aids and shared decision-making tools are needed to empower patients to make better-informed, self-efficacious VA decisions.
| S-EPMC8216296 | biostudies-literature
Project description:After stenosis of arteriovenous vascular access in hemodialysis patients, platelets play a crucial role in subsequent thrombus formation, leading to access failure. In a previous study, the mean platelet volume (MPV)/platelet count ratio, but not MPV alone, was shown to be an independent predictor of 4-year mortality after myocardial infarction. However, little is known about the potential influence of MPV/platelet count ratio on vascular access patency in hemodialysis patients. A total of 143 patients undergoing routine hemodialysis were recruited between January 2013 and February 2016. Vascular access failure (VAF) was defined as thrombosis or a decrease of greater than 50% of normal vessel diameter, requiring either surgical revision or percutaneous transluminal angioplasty. Cox proportional hazards model analysis ascertained that the change of MPV/platelet count ratio between baseline and 3 months [Δ(MPV/platelet count ratio)3mo-baseline] had prognostic value for VAF. Additionally, the changes of MPV/platelet count ratio over time were compared in patients with and without VAF by using linear mixed model analysis. Of the 143 patients, 38 (26.6%) were diagnosed with VAF. During a median follow-up of 26.9 months (interquartile range 13.0-36.0 months), Δ(MPV/platelet count ratio)3mo-baseline significantly increased in patients with VAF compared to that in patients without VAF [11.6 (6.3-19.0) vs. 0.8 (-1.8-4.0), P< 0.001]. In multivariate analysis, Δ(MPV/platelet ratio count)3mo-baseline was an independent predictor of VAF, after adjusting for age, sex, diabetes, hypertension, coronary artery disease, cerebrovascular disease, vascular access type, the presence of previous VAF, and antiplatelet drug use (hazard ratio, 1.15; 95% confidence interval, 1.10-1.21; P< 0.001). Moreover, a liner mixed model revealed that there was a significant increase of MPV/platelet count ratio over time in patients with VAF compared to those without VAF (P< 0.001). An increase in MPV/platelet count ratio over time was an independent risk factor for VAF. Therefore, continuous monitoring of the MPV/platelet count ratio may be useful to screen the risk of VAF in patients undergoing routine hemodialysis.
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Project description:Background and objectivesFistulas, the preferred form of hemodialysis access, are difficult to establish and maintain. We examined the effect of a multidisciplinary vascular access team, including nurses, surgeons, and radiologists, on the probability of using a fistula catheter-free, and rates of access-related procedures in incident patients receiving hemodialysis.Design, setting, participants, & measurementsWe examined vascular access outcomes in the first year of hemodialysis treatment before (2004-2005, preteam period) and after the implementation of an access team (2006-2008, early-team period; 2009-2011, late-team period) in the Calgary Health Region, Canada. We used logistic regression to study the probability of fistula creation and the probability of catheter-free fistula use, and negative binomial regression to study access-related procedure rates.ResultsWe included 609 adults (mean age, 65 [±15] years; 61% men; 54% with diabetes). By the end of the first year of hemodialysis, 102 participants received a fistula in the preteam period (70%), 196 (78%) in the early-team period (odds ratios versus preteam, 1.47; 95% confidence interval, 0.92 to 2.35), and 139 (66%) in the late-team period (0.85; 0.54 to 1.35). Access team implementation did not affect the probability of catheter-free use of the fistula (odds ratio, 0.87; 95% confidence interval, 0.52 to 1.43, for the early; and 0.89; 0.52 to 1.53, for the late team versus preteam period). Participants underwent an average of 4-5 total access-related procedures during the first year of hemodialysis, with higher rates in women and in people with comorbidities. Catheter-related procedure rates were similar before and after team implementation; relative to the preteam period, fistula-related procedure rates were 40% (20%-60%) and 30% (10%-50%) higher in the early-team and late-team periods, respectively.ConclusionIntroduction of a multidisciplinary access team did not increase the probability of catheter-free fistula use, but resulted in higher rates of fistula-related procedures.
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Project description:BACKGROUND:Arteriovenous fistulas (AVFs) are the preferred vascular access type in most hemodialysis patients. However, the optimal vascular access type in octogenarians and older (?80?years) hemodialysis patients remains widely debated given their limited life expectancy and lower AVF maturation rates. METHODS:Among incident hemodialysis patients receiving care in a large national dialysis organization during 2007-2011, we examined patterns of vascular access type conversion in 1 year following dialysis initiation in patients <80 versus ?80 years of age. Among a subcohort of patients ?80?years of age, we examined the association between vascular access type conversion and mortality using multivariable survival models. RESULTS:In the overall cohort of 100?804 patients, the prevalence of AVF/arteriovenous graft (AVG) as the primary vascular access type increased during the first year of hemodialysis, but plateaued thereafter. Among 8356 patients ?80?years of age and treated for >1 year, those with initial AVF/AVG use and placement of AVF from a central venous catheter (CVC) had lower mortality compared with patients with persistent CVC use. When the reference group was changed to patients who had AVF placement from a CVC in the first year of dialysis, those with initial AVF use had similar mortality. A longer duration of CVC use was associated with incrementally worse survival. CONCLUSIONS:Among incident hemodialysis patients ?80?years of age, placement of an AVF from a CVC within the first year of dialysis had similar mortality compared with initial AVF use. Our data suggest that initial CVC use with later placement of an AVF may be an acceptable option among elderly hemodialysis patients.
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Project description:Hemodialysis vascular access dysfunction is a major source of morbidity for patients with ESRD. Development of effective approaches to prevent and treat vascular access failure requires an understanding of the underlying mechanisms, suitable models for preclinical testing, systems for targeted delivery of interventions to maximize efficacy and minimize toxicity, and rigorous clinical trials that use appropriate outcome measures. This article reviews the substantial progress and ongoing challenges in developing novel treatments for arteriovenous vascular access failure and focuses on localized rather than systemic interventions.
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Project description:Hemodialysis vascular access dysfunction is a common and intractable problem in clinical practice with no definitive therapy yet available. As a key mediator of vascular and cardiac maladaptive remodeling, mineralocorticoid receptor (MR) plays a pivotal role in vascular fibrosis and intimal hyperplasia (IH) and is potentiated locally in hemodialysis vascular access following diverse injuries, like barotrauma, cannulation and shear stress. MR-related genomic and non-genomic pathways are responsible for triggering vascular smooth muscle cell activation, proliferation, migration and extracellular matrix overproduction. In endothelial cells, MR signaling diminishes nitric oxide production and its bioavailability, but amplifies reactive oxygen species, leading to an inflammatory state. Moreover, MR favors macrophage polarization towards a pro-inflammatory phenotype. In clinical settings like post-angioplasty or stenting restenosis, the beneficial effect of MR antagonists on vascular fibrosis and IH has been validated. In aggregate, therapeutic targeting of MR may provide a new avenue to prevent hemodialysis vascular access dysfunction.
| S-EPMC6354623 | biostudies-literature