Plastic cannulas mitigate arteriovenous fistula stenosis by suppressing the CFB-mediated inflammatory cascade

Effect of Buttonhole Cannulation With a Polycarbonate Peg on In-Center Hemodialysis Fistula Outcomes: A Randomized Controlled Trial

Pre-existing and Postoperative Intimal Hyperplasia and Arteriovenous Fistula Outcomes

The study of hemodynamic alterations following the creation of an arteriovenous fistula (AVF) is relevant to vascular adaptive responses and hemodialysis access dysfunction. This study examined such alterations in a murine AVF created by anastomosing the carotid artery to the jugular vein. AVF blood flow was markedly increased due to reduced AVF vascular resistance. Despite such markedly increased basal blood flow, AVF blood flow further increased in response to acetylcholine. This AVF model exhibited increased cardiac output and decreased systemic vascular resistance; the kidney, in contrast, exhibited decreased blood flow and increased vascular resistance. Augmentation in AVF blood flow was attended by increased arterial heme oxygenase-1 (HO-1) mRNA and protein expression, the latter localized to smooth muscle cells of the AVF artery; AVF blood flow was substantially reduced in HO-1(-/-) mice compared with HO-1(+/+) mice. Finally, in a murine model of a representative disease known to exhibit impaired hemodynamic responses (sickle cell disease), the creation of an AVF was attended by decreased AVF flow and impaired AVF function. We conclude that this AVF model exhibits markedly increased AVF blood flow, a vasodilatory reserve capacity, increased cardiac output, decreased renal blood flow, and a dependency on intact hemodynamic responses, in general, and HO-1 expression, in particular, in achieving and maintaining AVF blood flow. We suggest that these findings support the utility of this model in investigating the basis for and the consequences of hemodynamic stress, including shear stress, and the pathobiology of hemodialysis AVF dysfunction.

Preoperative arterial function is associated with arteriovenous fistula (AVF) development. Because arterial pathology may correlate with its function, preexisting arterial intimal hyperplasia may be associated with AVF development. Vascular specimens obtained from 125 patients (with minimal 2 mm arterial diameter and 2.5 mm venous diameter) undergoing AVF creation were quantified for arterial intimal hyperplasia, arterial medial fibrosis, arterial microcalcification, and venous intimal hyperplasia. A 6-week postoperative ultrasound quantified AVF diameter, blood flow, and stenosis. Clinical AVF maturation was assessed using a predefined protocol. In a prospective cohort study design, we investigated the association of preexisting arterial intimal hyperplasia with the postoperative AVF diameter, blood flow, stenosis, and clinical maturation failure, after controlling for baseline demographics, comorbidities, and preoperative vein diameter. Additional analyses evaluated whether other vascular pathologies interacted with arterial intimal hyperplasia in affecting AVF outcomes. The median intimal thickness of the native artery was 22.0 μm (interquartile range, 14.8-37.1 μm). The median postoperative AVF diameter was 4.8 (interquartile range, 3.7-6.8) mm, blood flow was 796 (interquartile range, 413-1036) ml/min, and stenosis was present in 37 out of 98 patients with ultrasound data (38%). AVF nonmaturation occurred in 37 out of 125 patients (30%). Preexisting arterial intimal thickness was not significantly associated with AVF blood flow (-12 ml/min; 95% confidence interval [95% CI], -55 to 30 ml/min), diameter (-0.04 mm; 95% CI, -0.21 to 0.14 mm), stenosis (odds ratio, 0.93; 95% CI, 0.75 to 1.14), or clinical maturation failure (odds ratio, 1.07; 95% CI, 0.90 to 1.28), all per 10 μm increase. There was no significant interaction of preexisting arterial intimal thickness and postoperative AVF outcomes with arterial medial fibrosis, arterial microcalcification, or venous intimal hyperplasia. Preexisting arterial intimal hyperplasia is not associated with the 6-week AVF blood flow, diameter or stenosis, or clinical maturation when the preoperative arterial diameter is ≥2 mm.

Key PointsThe rat arteriovenous fistula (AVF) model exhibits marked upregulation of p16Ink4a and p21Cip1 and multiple markers of senescence.Fisetin, an established vasoprotective senolytic agent, when administered for 3 weeks, increases AVF blood flow and AVF outward remodeling.Heme is shown to be a novel prosenescence metabolite, and when chronically administered, it decreases AVF blood flow.BackgroundMaturational failure of dialysis arteriovenous fistulas (AVFs) not uncommonly occurs and is of considerable and timely importance. Our prior studies demonstrate that senescence, a phenotypic process that promotes vascular and other diseases, occurs in the murine AVF. In this study, we examined whether senescence also occurs in the rat AVF model and the effect of compounds that inhibit or accelerate senescence.MethodsThe rat AVF was created in the femoral vessels by an end vein-side artery anastomosis. In the AVF, we assessed the expression of critical drivers of senescence, specifically, the cell cycle inhibitors p16Ink4a and p21Cip1, and such indices of a senescence phenotype as senescence-associated β-galactosidase (SA-β-gal) activity, SA-β-gal staining, and a senescence-associated secretory phenotype. We examined the effects of compounds that retard or accelerate senescence on AVF blood flow.ResultsThe AVF evinced upregulation of p16Ink4a and p21Cip1 when assessed 3 days after AVF creation. The AVF also demonstrated increased SA-β-gal activity in the artery and vein; staining for SA-β-gal in the AVF artery, anastomosis, and vein; and a prominent senescence-associated secretory phenotype. Fisetin, an established senolytic that is protective in other models of vascular injury, when administered for 3 weeks, increased AVF blood flow and outward remodeling. Hemin, when administered for 3 weeks, decreased AVF blood flow. We demonstrate that hemin is a novel inducer of a senescence phenotype in endothelial cells, as reflected by several senescence indices. However, when administered relatively acutely (for 5 days), hemin increased AVF blood flow by heme oxygenase–dependent mechanisms because the latter was entirely prevented by a competitive inhibitor of heme oxygenase activity.ConclusionsThe rat AVF exhibits senescence within 3 days of its creation. Chronic administration of a senolytic compound (fisetin) increases AVF blood flow, whereas chronic administration of a prosenescence compound (hemin) decreases AVF blood flow.

Background: A clinically tunneled cuffed catheter (TCC) for hemodialysis (HD) is often inserted into end-stage renal disease patients, who have an immature or no arteriovenous fistula (AVF), for the performance of HD to relieve uremic syndrome or to solve uncontrolled fluid overload, hyperkalemia, or metabolic acidosis. The catheter is primarily regarded as a bridge until the AVF matures and can be cannulated for HD. However, the effect of the bridge of the TCC on the future patency of AVFs remains elusive. Methods: This nationwide population-based observational study compared the hazards of AVF failure and the time to AVF failure. We enrolled 24,142 adult incident patients on HD, who received HD via AVFs for at least 90 days between 1 January 2010 and 31 December 2015. The subjects were divided into two groups, according to the history of TCC, and were followed-up until the failure of the AVF, mortality, or the end of the study. A propensity score-matched analysis based on 1:1 matching of age, sex, and baseline comorbidities was utilized to reduce bias and confounding variables. Results: A Kaplan–Meier survival curve revealed that patients with and without a history of TCC had significantly better AVF survival rates (log-rank test; p < 0.001). A history of TCC was independently associated with a higher risk of new AVF or AVG creation due to AVF failure, after the adjustment of the Charlson comorbidity index score (corresponding adjusted hazard ratios of 2.17 and 1.52; 95% confidence intervals of 1.77–2.67 and 1.15–1.99). For the impact of time on AVF failure, patients with a TCC bridge had a significantly higher incidence of new AVF creation during the first year after the AVF cannulation. Conclusion: A history of a TCC bridge was an independent risk factor for AVF failure and the time of AVF failure was significantly higher during the first year after the fistula cannulation in the TCC bridge group.

An arteriovenous fistula (AVF) can fail for different reasons at each stage after its creation. The study aimed to analyze the associations of the clinical and laboratory parameters, including the intraoperative AVF blood flow, with AVF failure at different periods (3 weeks and 3, 6, 9, 12, 24, and 36 months) after the AVF's creation and to evaluate the usefulness of the intraoperative AVF blood flow as a surrogate marker of AVF failure in patients with end-stage renal disease (ESRD). This was a single-center, retrospective cohort study that included 130 patients with ESRD who underwent the creation of new radiocephalic AVFs. The associations of the preoperative clinical and laboratory parameters and intraoperative flow with AVF failure in the different observation periods were investigated. Intraoperative AVF blood flow was significantly associated with AVF failure from 3 weeks to 24 months (P <0.05). Hemoglobin level and the size of the anastomosis were significantly associated with AVF failure at 6 months (P <0.05). In the analysis of the receiver operating characteristic curve, intraoperative AVF blood flow was significant from 3 weeks to 24 months (P <0.05). The intraoperative blood flow with the greatest sensitivity and specificity was 205-225 mL/min. Intraoperative blood flow was independently associated with AVF failure from 3 weeks to 24 months after the AVF's creation. An intraoperative AVF blood flow of >225 mL/min is crucial for long-term AVF patency. The intraoperative AVF blood flow level could be a surrogate marker of AVF failure in ESRD patients.

To the best of our knowledge, a possible predictive relationship between the systemic coagulation-inflammation index (SCI) and arteriovenous fistula (AVF) failure following AVF creation has not yet been examined. We therefore designed this study to examine the predictive ability of SCI on postoperative early AVF failure in patients undergoing primary radiocephalic AVF operation. A total of 189 patients who underwent primary radiocephalic AVF operation for hemodialysis access were included in this retrospective observational cohort study, and then divided into two groups according to whether AVF failure occurred within the first 3 months after the operation; as failed AVF group (n = 44) and non-failed AVF group (n = 145). The patients' baseline clinical characteristics and laboratory parameters were recorded and then compared between the groups. Patients in failed AVF group were significantly older and had higher smoking rate than those in non-failed AF group. The median values of fibrinogen, platelet-to-lymphocyte ratio and SCI were significantly higher in failed AVF group than in non-failed AVF group. With regards to other clinical characteristics and laboratory parameters, no significant differences were detected between the groups in the univariate analyses. Only age and SCI maintained their significances in the multivariate logistic regression analysis, and were therefore considered as the independent predictors of AVF failure. ROC curve analysis revealed that SCI of 37.9 constituted the optimum cut-off value with 97.7% sensitivity and 94.5% specificity rates for predicting AVF failure. The present study demonstrated for the first time in the literature that SCI significantly and independently predicted early AVF failure following radiocephalic AVF creation.

Cellular effects of garlic supplements and antioxidant vitamins in lowering marginally high blood pressure in humans: pilot study

Pulmonary hypertension (PH) is common in patients with end-stage renal disease (ESRD). Arteriovenous fistulas (AVF) creation may involve in the pathogenesis of PH. The aim of this study was to explore the impact of PH after AVF creation on the AVF failure rate in maintenance hemodialysis (MHD) patients. From January 1, 2009, to January 1, 2019, we retrospectively collected data of 578 MHD patients in Guangdong Provincial People's Hospital Blood Purification Center, China. Patients were followed-up until AVF failure or death or May 25, 2020. According to the systolic pulmonary artery pressure (SPAP) within 1 year after the establishment of AVF, the MHD patients were divided into three groups: SPAP ⩽ 35 mmHg, 35 < SPAP < 45 mmHg, SPAP ⩾ 45 mmHg. The primary outcome was AVF failure defined as AVF cannot complete hemodialysis. The secondary outcomes were all-cause mortality. A total of 578 patients were analyzed. The average age was 60.66 ± 15.34 years (58.1% men). Of these, 26.1% of patients were reported PH. The SPAP exhibited a left-skewed nonparametric distribution and the overall SPAP after the creation of AVF was 39.00 (29.00-52.00) mmHg. The median follow-up was 5.8 (5.5-6.3) years. Overall, 12.8% (74/578) patients were reported AVF failure events. There was no significant difference in AVF failure rate among three groups (p = 0.070). A total of 111 (19.2%) died during the follow-up period. Compared with the SPAP ⩽35 mmHg group, only the all-cause death rate significantly increased in MHD patients with PH (p < 0.001). The secondary pulmonary hypertension after AVF creation did not increase the risk of AVF failure in MHD patients, but significantly increased the risk of mortality for this portion of the patients. Future larger sample sizes, multi-center, and prospective trials are needed to make sure which type of access will benefit on their survival for MHD patients with SPAP ⩾35 mmHg.

Arteriovenous fistula (AVF) is vascular access created for hemodialysis in end-stage renal disease patients. AVF creation causes increased blood flow in the outflow vein with increased pressure. Increased blood flow, blood volume, and shear stress causes outward remodeling so that the outflow vein can withstand the increased pressure. Outward remodeling of the vein involved in AVF is necessary for AVF maturation, however, inward remodeling due to excessive neointimal hyperplasia (NIH) and chronic inflammation may end up with vessel thrombosis and AVF maturation failure. Early thrombosis of the vessel may be due to the luminal factors including NIH and chronic inflammation or due to chronic inflammation of the adventitial due to perivascular cuffing. Inflammation may either be due to an immune response to the vascular injury during AVF creation or injury to the surrounding muscles and fascia. Several studies have discussed the role of inflammation in vascular thrombosis due to intimal injury during AVF creation, but there is limited information on the role of inflammation due to surrounding factors like a muscle injury. The concept of perivascular cuffing has been reported in the nervous system, but there is no study of perivascular cuffing in AVF early thrombosis. We performed the bulk RNA sequencing of the femoral arterial tissue and contralateral arteries as we found thrombosed arteries after AVF creation. RNA sequencing revealed several significantly differentially expressed genes (DEGs) related to chronic inflammation and perivascular cuffing, including tripartite motif-containing protein 55 (TRIM55). Additionally, DEGs like myoblast determination protein 1 (MYOD1) increased after muscle injury and relates to skeletal muscle differentiation, and network analysis revealed regulation of various genes regulating inflammation via MYOD1. The findings of this study revealed multiple genes with increased expression in the AVF femoral artery and may provide potential therapeutic targets or biomarkers of early thrombosis in AVF maturation failure. Thus, not only the luminal factors but also the surrounding factors mediating vascular cuffing contribute to vessel thrombosis and AVF failure via early thrombosis, and targeting the key regulatory factors may have therapeutic potential.

Non-nutritive sweeteners (NNS), such as sucralose and acesulfame potassium (ace K), offer low-calorie alternatives to traditional sweeteners, such as glucose and fructose. Substituting NNSs for these traditional sweeteners, particularly in popular beverages such as soft drinks, has been shown to help mitigate some, not all, of sugar-associated cardiometabolic risk. However, the effect of NNSs on endothelial cell function are not fully understood. The experimental aim of this study was to determine if sucralose and ace k affects endothelial cell inflammation, apoptosis and nitric oxide (NO) production, key functional properties of vascular health. Human umbilical vein endothelial cells were cultured and treated with concentrations of sucralose (0.169mg/mL) and/or ace k (0.127mg/mL) that are equivalent to the amount in one 12 oz can of diet soda (i.e. Diet Coke with Splenda or Pepsi One) for 24 h. Neither sucralose, ace k, nor sucralose + ace k significantly altered markers of endothelial cell inflammation. Total cellular expression of the primary inflammation transcription factor, nuclear factor kappa B (NF-kB) was not different in endothelial cells treated with sucralose (46.0±10.6 AU), ace k (41.3±17.4 AU), sucralose + ace k (47.9±15.4 AU) or control (50.8±15.7 AU). Activated NF-kB was also similar in cells treated with sucralose (130.1±29.6 AU), ace k (122.0±32.4 AU), sucralose + ace k (118.4±33.5 AU) and control (116.7±16.3 AU). In addition, NNSs did not affect endothelial cell apoptosis. Total caspase 3 expression, a key apoptosis protein, was not significantly different between sucralose (65.1±14.0 AU), ace k (78.8±5.4 AU), sucralose + ace k (59.0±9.4 AU) and control (88.1±14.7 AU) conditions. Of note, the expression of active caspase 3 was also not significantly different between sucralose (13.0±3.0 AU), ace k (12.2±3.2 AU), sucralose + ace k (11.8±3.3 AU) and control (11.7±1.6 AU). Endothelial nitric oxide synthase (eNOS) is fundamental to endothelial cell function and the production of NO. Total eNOS expression was not significantly different in cells treated with sucralose (155.5±22.6 AU), ace k (260.9±53.5 AU), sucralose + ace k (175.3±36.3 AU) or control (245.3±27.0 AU); however, sucralose (180.9±36.9 AU), ace k (208.0±40.2 AU) and sucralose + ace k (115.1±17.5 AU) markedly lowered (P<0.05) eNOS activation (phosphorylated-(p)eNOS serine 1177) compared with the control condition (375.9±74.6 AU). Concordantly, NO production was significantly reduced in cells treated with sucralose (7.5±0.4 mmol/L), ace k (7.9±0.2 mmol/L), and sucralose + ace k (6.9±0.2 mmol/L) compared with control (9.1±0.5 mmol/L). The effect of NSSs on p-eNOS and NO production was similar across the conditions. In conclusion, NNSs commonly contained in artificially sweetened beverages do not affect specific endothelial cell inflammation or apoptotic proteins, however NNSs adversely affect endothelial cell nitric oxide production. Future studies are needed to determine whether NNS are associated with impaired endothelial vasodilator dysfunction and the potential vascular consquences of reduced NO bioavailabilty.

Introduction: Arterio Venous Fistulas (AVFs) may be radiocephalic, brachiocephalic or brachiobasilic, however a radio-cephalic access is preferred for patients with end stage renal disease requiring haemodialysis. After their creation, the minimum time for AVF maturation is around two months. Primary AVF failure is defined as an AV fistula that is never usable or fails within the first three months of its use. There are several observations that indicate the role of inflammation in failure of AVF. Elevated CRP has been observed to be associated with early fistula failure and our study purported to correlate the same. Methodology: In this pilot study, 50 patients of end stage renal disease (ESRD) over 18 years of age, after fulfilling inclusion and exclusion criteria, underwent the creation of a radio-cephalic AVF. All patients had pre-operative values of CRP, haemoglobin and albumin estimated, which were repeated again on post-operative day 2. All patients were followed for three months to assess for primary failure of fistula. Results: Out of the 50 patients included in the study, six patients were lost to follow up. The mean age of the patients was 41.48 ±13.46 years. 31.8% (14 patients) developed primary failure of the AVF. No significant correlation was identified between primary failure of AVF and the pre-operative hemoglobin and albumin levels. While a pre-operative CRP level 5.4 mg/dl (p=0.025, Sn: 71.43%, Sp: 66.7%). Number of dialysis per week through other sites, and comorbidities like hypertension and diabetes mellitus did not show any significant association with primary failure of AVF. Conclusion: Pre-operative CRP levels>5.4 mg/dl can predict the primary failure of AVF with a sensitivity of 71.43% and specificity of 66.7%. However further studies are required to validate the same.

PREDICTING HIGH FLOW ARTERIOVENOUS FISTULAS AND CARDIAC OUTCOMES IN HEMODIALYSIS PATIENTS.

Background: Arteriovenous fistula (AVF) failure rates are consistently higher in females, although the underlying mechanisms remain incompletely understood. Inflammatory processes play a key role in AVF remodeling and venous arterialization, yet their influence may differ by sex. This study aimed to evaluate the impact of inflammatory indices on AVF blood flow and maturation, with a focus on sex-specific differences. Methods: This retrospective analytical study included 110 patients (50 females, 60 males) undergoing initial surgical AVF creation. Postoperative assessments occurred at the fourth and sixth weeks. Patients demonstrating insufficient maturation (blood flow < 600 mL/min) at the fourth week were re-evaluated after two weeks without any intervening procedures or additional interventions. Results: Intraoperative Transit-Time Flow Measurement (TTFM) revealed significantly higher median AVF blood flow in males compared to females (289 mL/min vs. 200 mL/min; p < 0.001). Doppler ultrasonography (DUS) findings confirmed these sex-related differences, demonstrating consistently lower blood flow rates in female patients. An elevated neutrophil-to-lymphocyte ratio (NLR) was associated with approximately a 31% reduction in AVF blood flow among females, whereas an increased C-reactive protein-to-albumin ratio (CrA) correlated with an approximate 9% decline. In males, an elevated systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were significantly associated with decreased AVF blood flow. Conversely, a higher prognostic nutritional index (PNI) positively correlated with AVF blood flow in both sexes. Risk factors associated with inadequate AVF maturation (<600 mL/min at sixth week) included female sex, advanced age, obesity, smoking, anemia, low vitamin D levels, and elevated inflammatory indices (NLR, SII, and SIRI). Conclusions: Inflammatory and nutritional indices derived from routine laboratory tests may assist in estimating AVF maturation likelihood. While DUS reliably assesses AVF blood flow, complementary evaluation methods may be required to assess the broader vascular status. Further research is needed to clarify sex-specific inflammatory mechanisms influencing AVF outcomes and to guide individualized management strategies.