Arteriovenous Fistula Failure In Hemodialysis Patients Research Articles

Analysis of risk factors for late arteriovenous fistula failure and patency rates after angioplasty in hemodialysis patients: a retrospective cohort study.

The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing worldwide. Hemodialysis (HD) is the mainstay of renal replacement therapy for patients with ESKD. Risk factors associated with late arteriovenous fistula (AVF) failure in HD patients are poorly investigated. Therefore, the aim of this study was to identify factors associated with late AVF failure in HD patients. Patients with end-stage renal disease (ESRD) who underwent forearm or upper arm AVF angioplasty at Second Affiliated Hospital of Chongqing Medical University between September 2009 and August 2018 were included. Patients were followed up for 36 months. Baseline characteristics were collected using electronic medical records (EMRs). Variables associated with late AVF failure were identified using Cox proportional hazards models. There were 137 patients (64% male, 36% female) included in this study, with 50 (36.5%) experiencing AVF failure. Univariable log-rank analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), intact parathyroid hormone (iPTH), albumin (ALB), and AVF patency rate were significantly different between patients who did and did not experience AVF failure. Cox regression analysis showed that CRP [P=0.002, hazard ratio (HR) =2.719, 95% confidence interval (CI) for HR: 1.432-5.164], ESR (P=0.030, HR =2.431, 95% CI: 1.088-5.434), iPTH (P=0.013, HR =0.325, 95% CI: 0.133-0.793), and ALB (P=0.040, HR =0.539, 95% CI: 0.299-0.972) were independently associated with AVF failure. Kaplan-Meier survival analysis showed that the cumulative patency rates of AVF at 6, 12, 18, 24, 30, and 36 months were 84%, 74%, 69%, 64%, 64%, and 64%, respectively. CRP, ESR, iPTH, and ALB were associated with AVF failure and should be used as reference in clinical practice.

Association of platelet and hematocrit value with arteriovenous fistula (AVF) failure in hemodialysis patient at Bali Husada Cipta Canti, Bali, Indonesia

Introduction: Hemodialysis is one of the renal replacement therapies used for end-stage renal disease (ESRD) patients. Arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, around 31-61% of AVF fail to mature. An early AVF failure may be due to a lack of maturation or thrombosis, and late failure defines as a failure after successful use. Some factors that make AVF fail are injury of the endothelial wall or hypercoagulation. This study aimed to determine the association between pre-operative platelet and hematocrit value with AVF failure in BHCC Clinic Denpasar. Method: This is an analytic cross-sectional study. The data were collected from medical records from all dialytic patients from January 2020-December 2020. Patients with inclusion criteria were collected. Patient with incomplete data was excluded. Data were analyzed using Chi-square analysis. Results: Our study involved 34 patients, 21(61.8%) of them were male, and the mean age was 52.62 years (±10.77 SD). The AVF failure prevalence was 32.4% (n=11). We found no association between platelet value with AVF failure, with a p-value=0.411. There was an association between hematocrit value and AVF failure in hemodialysis patients with a p-value=0.032. Most of the patient was male and aged 45-60 with ESRD from the characteristic found. Conclusion: There was an association between pre-operative hematocrit value and AVF failure in hemodialysis patients. There was no association between pre-operative platelet value with AVF failure.

Risk Factors for Primary Arteriovenous Fistula Dysfunction in Hemodialysis Patients: A Retrospective Survival Analysis in Multiple Medical Centers

Background: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis (HD). However, primary AVF dysfunction represents a major barrier to the long-term success of HD therapy. This study aims to analyze the variables that influence the incidence of first AVF failure in HD patients. Methods: From January 2012 to October 2016, a total of 100 HD subjects from 43 medical centers were enrolled for a retrospective survival analysis of AVF dysfunction. To diminish the potential influence of surgeon experiences, the same operation group in Second Xiangya Hospital performed all studied AVF placements. This study focuses on a Chinese population of idiopathic glomerular disease to avoid the secondary influence of other systemic diseases, including diabetes, hypertension, and autoimmune disorder. AVF dysfunction was defined as lower blood flow during dialysis (≤200 mL/min) or insufficiency of HD treatment caused by reduced blood flow. Results: Among all enrolled subjects, the incidence of AVF dysfunction due to impatency was 27% (n = 27) with a cumulative survival of 84.0, 73.1, and 71.6% in 6, 12, and 24 months of post-placement. AVF survival ­analysis revealed a higher incidence of AVF failure in females (p= 0.025) and elderly (p = 0.031) patients. Importantly, AVF dysfunction markedly increased in subjects with higher levels of platelets (PLTs; p = 0.024), severe anemia (p = 0.014), and extended temporary catheter retention (p = 0.020). Further multivariate Cox regression analysis confirmed these variables as independent risk factors for first AVF dysfunction. Meanwhile, no significant difference could be observed according to the levels of body mass index, serum albumin, serum calcium, serum phosphorus, prothrombin time, and activated partial thromboplastin time. Lastly, anti-coagulant treatments seemed to barely influence the outcomes of AVF survival in this study. Conclusion: These findings suggest that primary AVF dysfunction in HD patients is associated with gender, ageing, PLT counting number, hemoglobin level, and retention time of temporary catheter.

Oral prostacycline analog and clopidogrel combination provides early maturation and long-term survival after arteriovenous fistula creation: A randomized controlled study.

Vascular access is used as a lifeline for hemodialysis in patients with end stage renal disease failure (ESRD). Failure of arteriovenous fistula (AVF) maturation is still high. The purpose of this study was to research the effects of clopidogrel in combination with oral iloprost, a synthetic analog of prostacyclin PGI2. Ninety-six diabetic ESRD patients were divided into two groups. In the first group (Group 1, N = 50), clopidogrel (75 mg daily dose) and an oral prostacycline analog (200 mg daily dose) were administered. In the second group (Group 2, N = 46), placebo was given. All patients took study medication 7–10 days prior to surgery. A Doppler ultrasound (USG) was performed for measurement of arterial and venous diameters, and peak systolic velocity of arterial flow based on subsequent fistula adequacy. Autogenous AVFs were constructed in forearm as distally as possible in all patients. Both groups were followed-up for a year. In the placebo group, early AVF thrombosis was detected in two patients (4.3%). AVF maturation failure was noted in 14 patients (30.4%) in placebo group and in four patients (8%) in clopidogrel plus oral prostacycline analog group in the early postoperative period (P = 0.001). The mean maturation time was 38 ± 6.5 and 53 ± 12.8 days in study and placebo groups, respectively (P = 0.023). The mean blood flow was 352 ± 94 mL/min in placebo group and 604 ± 125 mL/min in study group (P = 0.001). The arterial end diastolic velocity was 116 ± 14 cm/s in study group and 72 ± 21 cm/s in placebo group (P = 0.036) 1 year after the surgery. Our data indicated that clopidogrel and oral prostacycline analog combination is effective and safe for the prevention of primary AVF failure in hemodialysis patients and decreased acute and chronic thrombotic events.

Ticlopidine to prevent primary arteriovenous fistula failure in hemodialysis patients; a randomized controlled trial.

Implication for health policy/practice/research/medical education:Primary arteriovenous fistula (AVF), failure remains a major problem for hemodialysis patients. Vascular access thrombosis prophylaxis needs to start early in the end-stage renal disease patient. Ticlopidine seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients.

Implementation of predictive data mining techniques for identifying risk factors of early AVF failure in hemodialysis patients.

Arteriovenous fistula (AVF) is an important vascular access for hemodialysis (HD) treatment but has 20–60% rate of early failure. Detecting association between patient's parameters and early AVF failure is important for reducing its prevalence and relevant costs. Also predicting incidence of this complication in new patients is a beneficial controlling procedure. Patient safety and preservation of early AVF failure is the ultimate goal. Our research society is Hasheminejad Kidney Center (HKC) of Tehran, which is one of Iran's largest renal hospitals. We analyzed data of 193 HD patients using supervised techniques of data mining approach. There were 137 male (70.98%) and 56 female (29.02%) patients introduced into this study. The average of age for all the patients was 53.87 ± 17.47 years. Twenty eight patients had smoked and the number of diabetic patients and nondiabetics was 87 and 106, respectively. A significant relationship was found between “diabetes mellitus,” “smoking,” and “hypertension” with early AVF failure in this study. We have found that these mentioned risk factors have important roles in outcome of vascular surgery, versus other parameters such as “age.” Then we predicted this complication in future AVF surgeries and evaluated our designed prediction methods with accuracy rates of 61.66%–75.13%.

Superoxide in AVF dysfunction: a new target for intervention

Editorial FocusSuperoxide in AVF dysfunction: a new target for interventionAbolfazl Zarjou, and Anupam AgarwalAbolfazl ZarjouDivision of Nephrology, Department of Medicine, Nephrology Research and Training Center and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama; and , and Anupam AgarwalDivision of Nephrology, Department of Medicine, Nephrology Research and Training Center and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Veterans Affairs Medical Center, Birmingham, AlabamaPublished Online:15 Dec 2012https://doi.org/10.1152/ajprenal.00549.2012This is the final version - click for previous versionMoreSectionsPDF (122 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat an adequately functioning vascular access is an absolute requisite for patients receiving hemodialysis. Among the three currently available (fistulae, grafts, and tunneled catheters) vascular accesses, the arteriovenous fistula (AVF) is considered the “gold standard” and is the most common mode of vascular access (9, 16). AVF has several advantages that include lower risk of infections and clot formation, better blood flow, and hence superior effectiveness of dialysis and higher longevity compared with other vascular access modalities (16). Nevertheless, the rates of inadequate AVF maturation and functional failure are alarmingly high (16). Such failure rates translate to significant morbidity, hospitalization, and mortality. Furthermore, the yearly health care costs for vascular access-related morbidity are well over one billion dollars in the United States alone (2, 11). The number of patients requiring hemodialysis has increased remarkably in the past few decades. Therefore, there is an urgent need to study the underlying mechanisms of AVF dysfunction to enable implementation of novel preventive and therapeutic strategies to improve quality of care in hemodialysis patients.The major cause of AVF failure is either unsuccessful maturation or venous stenosis of a matured AVF. Although several mechanisms have been proposed for AVF malfunction, venous stenosis resulting from neointimal hyperplasia within the perianastomotic region is undoubtedly the most common cause of AVF failure in hemodialysis patients. Despite the magnitude of this clinical challenge, there are no effective preventive and/or therapeutic measures to adequately address this condition. In an attempt to decipher the pathobiological pathways that lead to AVF venous stenosis and AVF failure, animal models have been designed that closely mimic the human lesion and hemodynamic features (1, 5, 7). These studies demonstrate that the venous stenosis is associated with several pathological characteristics such as smooth muscle cell migration and proliferation, monocyte/macrophage infiltration, fibrosis, and microangiogenesis that may be accompanied by thrombosis and/or calcification and upregulation of a number of inflammatory genes (10–12).While a strong body of evidence suggests that disproportionate reactive oxygen species, in particular superoxide anions, are involved in the pathogenesis of a number of vascular injury and remodeling conditions (3, 4, 13), whether such derangements could account for the AVF failure has not been comprehensively explored. In an issue of the American Journal of Physiology-Renal Physiology, Tsapenko and colleagues (15) investigated the pathogenic role of superoxide anion in venous stenosis in a rat model of femoral AVF. The authors report significant augmentation of superoxide anion levels at one week postcreation of the AVF in the venous limb. Such increment was attributed to both increased generation and decreased dismutation of the superoxide anions due to reduced total superoxide dismutase expression and activity. Superoxide dismutase is an antioxidant enzyme that converts two superoxide anions into a molecule of hydrogen peroxide (decomposed and neutralized by glutathione peroxidase and catalase) and one molecule of oxygen. This concept was further validated by either unchanged or increased levels of glutathione peroxidase and catalase, respectively. Interestingly, the authors also report evidence of significant tyrosine nitration in all three layers of the veins as well as infiltrating leukocytes in the AVF. This observation highlights the increased generation of peroxynitrite, a product of superoxide anion interaction with nitrogen oxide. Under a number of pathological conditions, nitric oxide synthase (NOS) activity becomes uncoupled, leading to increased production of superoxide anion. Indeed, NOS uncoupling has been implicated in vasculopathies such as atherosclerosis. To validate evidence of such uncoupling, the authors demonstrate that the tetrahydrobiopterin (BH4)-to-dihydrobiopterin (BH2) ratio (a reliable marker of NOS uncoupling) is significantly reduced in the venous segment of the AVF.To elucidate other downstream effects of increased superoxide anion generation, several potential candidate pathways were investigated. Intriguingly, only Src and its phosphorylated form were markedly elevated. Because Src is involved both up- and downstream of superoxide anion, these results suggest a vicious cycle of superoxide anion generation and positive feedback that further instigates the cycle. Moreover, the significance and the potential of mitigating the markedly increased superoxide anions as a therapeutic target were also elegantly deciphered. Administration of tempol, a well-known membrane-permeable radical scavenger with potent antioxidant properties, significantly improved the histological changes, AVF patency, and, at higher doses, also augmented blood flow through the AVF.The findings by Tsapenko and colleagues elaborately describe the role of oxidative stress in AVF dysfunction. This increase in oxidative stress, as a result of augmented superoxide anion, induces the antioxidant enzyme heme oxygenase-1 (HO-1). HO-1 catalyzes the breakdown of heme into equimolar quantities of iron, carbon monoxide, and biliverdin (14). Biliverdin is further reduced to bilirubin by biliverdin reductase. Both bile pigments are capable of scavenging peroxy radicals while carbon monoxide can induce vasodilation. Therefore, HO-1 induction, as an adaptive response to injury, is critical for protection against AVF dysfunction. In fact, a previous study from the laboratory of Juncos et al. demonstrated the induction of HO-1 in a murine model of AVF (6). The beneficial significance of such induction was highlighted by premature failure of AVF in HO-1−/− mice (6). Furthermore, these results are corroborated in patients with HO-1 gene polymorphisms [dinucleotide GT repeat (GT)(n) in the promoter region] (8). The longer-length GT repeats are associated with decreased HO-1 expression and a higher propensity of AVF access failure and worse patency (8).In summary, the findings by Tsapenko and colleagues (15) provide a novel pathological link between superoxide, Src activation, and AVF patency (Fig. 1). They provide biochemical evidence for the role of BH4 and BH2 in the uncoupling of NOS that results in increased generation of superoxide anion and that scavenging of superoxide with tempol improved AVF dysfunction. They also provide a link between Src kinase and aggravation of oxidative stress, leading to intimal hyperplasia and AVF failure. This study will certainly stimulate further research into the development of novel therapeutics to target key signaling pathways demonstrated in this study to prevent AVF dysfunction and improve AVF patency. Given the presence of heightened oxidative stress and inflammation in end-stage renal disease, these redox pathways would be relevant to target to prolong the lifespan of vascular access in dialysis patients.Fig. 1.Oxidative stress pathways in arteriovenous fistula (AVF) dysfunction. Increased superoxide anion in the venous limb of AVF can activate Src, which in turn can increase superoxide generation. Uncoupling of nitric oxide synthase (NOS), hemodynamic stress, and inflammatory mediators can also contribute to increase superoxide generation. Tempol, a scavenger of superoxide anion, and potentially other antioxidants can block this pathway, leading to attenuation of AVF dysfunction. SOD, superoxide dismutase.Download figureDownload PowerPointDISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the authors.AUTHOR CONTRIBUTIONSAuthor contributions: A.Z. interpreted results of experiments; A.Z. and A.A. prepared figures; A.Z. and A.A. drafted manuscript; A.Z. and A.A. edited and revised manuscript; A.Z. and A.A. approved final version of manuscript; A.A. conception and design of research.ACKNOWLEDGMENTSThis work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01 DK-59600 and the O'Brien Center P30 DK-079337 (to A. Agarwal).REFERENCES1. Croatt AJ , Grande JP , Hernandez MC , Ackerman AW , Katusic ZS , Nath KA. Characterization of a model of an arteriovenous fistula in the rat: the effect of l-NAME. Am J Pathol 176: 2530–2541, 2010.Crossref | PubMed | ISI | Google Scholar2. Feldman HI , Kobrin S , Wasserstein A. Hemodialysis vascular access morbidity. J Am Soc Nephrol 7: 523–535, 1996.Crossref | PubMed | ISI | Google Scholar3. Forstermann U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch 459: 923–939, 2010.Crossref | PubMed | ISI | Google Scholar4. Jeremy JY , Yim AP , Wan S , Angelini GD. Oxidative stress, nitric oxide, and vascular disease. J Card Surg 17: 324–327, 2002.Crossref | PubMed | ISI | Google Scholar5. Johnson MS , McLennan G , Lalka SG , Whitfield RM , Dreesen RG. The porcine hemodialysis access model. J Vasc Interv Radiol 12: 969–977, 2001.Crossref | PubMed | ISI | Google Scholar6. Juncos JP , Tracz MJ , Croatt AJ , Grande JP , Ackerman AW , Katusic ZS , Nath KA. Genetic deficiency of heme oxygenase-1 impairs functionality and form of an arteriovenous fistula in the mouse. Kidney Int 74: 47–51, 2008.Crossref | PubMed | ISI | Google Scholar7. Kelly BS , Heffelfinger SC , Whiting JF , Miller MA , Reaves A , Armstrong J , Narayana A , Roy-Chaudhury P. Aggressive venous neointimal hyperplasia in a pig model of arteriovenous graft stenosis. Kidney Int 62: 2272–2280, 2002.Crossref | PubMed | ISI | Google Scholar8. Lin CC , Yang WC , Lin SJ , Chen TW , Lee WS , Chang CF , Lee PC , Lee SD , Su TS , Fann CS , Chung MY. Length polymorphism in heme oxygenase-1 is associated with arteriovenous fistula patency in hemodialysis patients. Kidney Int 69: 165–172, 2006.Crossref | PubMed | ISI | Google Scholar9. Lok CE. Fistula first initiative: advantages and pitfalls. Clin J Am Soc Nephrol 2: 1043–1053, 2007.Crossref | PubMed | ISI | Google Scholar10. Roy-Chaudhury P , Kelly BS , Narayana A , Desai P , Melhem M , Munda R , Duncan H , Heffelfinger SC. Hemodialysis vascular access dysfunction from basic biology to clinical intervention. Adv Ren Replace Ther 9: 74–84, 2002.Crossref | PubMed | Google Scholar11. Roy-Chaudhury P , Kelly BS , Zhang J , Narayana A , Desai P , Melham M , Duncan H , Heffelfinger SC. Hemodialysis vascular access dysfunction: from pathophysiology to novel therapies. Blood Purif 21: 99–110, 2003.Crossref | PubMed | ISI | Google Scholar12. Roy-Chaudhury P , Sukhatme VP , Cheung AK. Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint. J Am Soc Nephrol 17: 1112–1127, 2006.Crossref | PubMed | ISI | Google Scholar13. Touyz RM , Schiffrin EL. Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol 122: 339–352, 2004.Crossref | PubMed | ISI | Google Scholar14. Tracz MJ , Alam J , Nath KA. Physiology and pathophysiology of heme: implications for kidney disease. J Am Soc Nephrol 18: 414–420, 2007.Crossref | PubMed | ISI | Google Scholar15. Tsapenko MV , d'Uscio LV , Grande JP , Croatt AJ , Hernandez MC , Ackerman AW , Katusic ZS , Nath KA. Increased production of superoxide anion contributes to dysfunction of the arteriovenous fistula. Am J Physiol Renal Physiol (First published September 19, 2012). doi:10.1152/ajprenal.00449.2012.Link | ISI | Google Scholar16. Vazquez MA. Vascular access for dialysis: recent lessons and new insights. Curr Opin Nephrol Hypertens 18: 116–121, 2009.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: A. Agarwal, Division of Nephrology, THT 647, Univ. of Alabama at Birmingham, 1530 3rd Ave. South, Birmingham, AL 35294 (e-mail: [email protected]edu). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByLess primary fistula failure in hypertensive patients27 March 2018 | Journal of Human Hypertension, Vol. 32, No. 4Functioning of an arteriovenous fistula requires heme oxygenase-2Lu Kang, Joseph P. Grande, Gianrico Farrugia, Anthony J. Croatt, Zvonimir S. Katusic, and Karl A. Nath15 August 2013 | American Journal of Physiology-Renal Physiology, Vol. 305, No. 4 More from this issue > Volume 303Issue 12December 2012Pages F1599-F1600 https://doi.org/10.1152/ajprenal.00549.2012PubMed23034943History Received 25 September 2012 Accepted 3 October 2012 Published online 15 December 2012 Published in print 15 December 2012 Metrics

Malnutrition, Infection and Arteriovenous Fistula Failure: Is There a Link?

The histology of neointimal hyperplasia, the primary cause of arteriovenous fistula (AVF) stenosis, resembles the histology of atherosclerosis. We evaluated classic atherogenic risk factors such as hypertension, smoking, diabetes, cholesterol, and evaluated the role of expanded risk factors such as: cytomegalovirus (CMV), Helicobacter pylori (H. pylori), Chlamydia pneumoniae (C. pneumoniae), infection, and malnutrition, as possible causes of AVF failure in hemodialysis (HD) patients. AVF of 91 HD patients were monitored by on-line blood flow measurement (Qac); levels of albumin, fibrinogen, C-reactive protein and plasma cholesterol were recorded. Nutrition was evaluated via the Malnutrition Inflammation Score and the normalized protein intake (nPCR). Seropositivity to CMV, C. pneumoniae and H. Pylori were assessed. Twenty-one patients had at least one episode of vascular access thrombosis; 17 patients had stenotic lesions. Analysis of survival tables revealed that patients who had high IgG CMV antibody levels had a higher probability of AVF failure than patients with lower CMV antibody levels. The difference in the empirical survival functions was statistically significant when we stratified by CMV antibody levels, unlike H. pylori or C. pneumoniae. In a logistic regression model, CMV, increased cholesterol, and decreases in nPCR and Qac significantly increased the risk of AVF failure. Our study suggests that CMV infection, total plasma cholesterol, decreased Qac, and nPCR are important risk factors of AVF failure in HD patients.

Randomized controlled trial of clopidogrel to prevent primary arteriovenous fistula failure in hemodialysis patients

The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula (AVF). Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure. A double-blind, randomized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients. Ninety three patients were randomized to receive 75 mg/daily of clopidogrel or placebo. The treatment was initiated 7–10 days prior to scheduled access surgery and continued up to six weeks postoperatively, and then patients were monitored for six months. The primary outcome was AVF failure eight weeks after fistula creation. With a permuted block randomization schedule, 46 patients received clopidogrel and 47 patients received control placebo. The primary AVF failures at two months were 21.6% in placebo group and 5.2% in clopidogrel group (P = 0.03). The hazard ratio for the incidence of primary AVF failure was 0.72 (CI 95%, 0.41–1.01). Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration. First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group (P = 0.008). No life-threatening adverse event or severe bleeding was recorded in both groups. Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients.

Local Activation of Interleukin 6 Signaling Is Associated With Arteriovenous Fistula Stenosis in Hemodialysis Patients

Vascular access failure is the main cause of morbidity in hemodialysis patients. Stenosis of the arteriovenous fistula (AVF) is similar histologically to atherosclerosis. Recent studies showed that interleukin 6 (IL-6) has a key role in the pathogenesis of atherosclerosis by binding 2 specific receptors, gp80 and gp130. When activated, gp130 interacts with a tyrosine kinase, Janus kinase (JAK2), which then activates a transcription factor, signal transducers and activators of transcription (STAT3), directly turning on several proinflammatory genes. The aim of this study is to evaluate gp130 expression and JAK2/STAT3 activation within stenotic AVFs. 44 patients undergoing surgery for AVF creation were enrolled; 10 of them had AVF failure with histologically proven AVF stenosis (wall-lumen ratio > 1). A venous fragment of the AVFs was collected during creation and revision of the vascular access. gp130 and gp80 expression, as well as JAK/STAT activation, were evaluated by means of confocal microscopy. Peripheral-blood mononuclear cells were isolated at the time of AVF creation and revision. gp130 protein expression, barely detectable in native AVFs, was strikingly increased within the venous branch of stenotic AVFs. The signaling subunit of the IL-6 receptor broadly colocalized with gp80, the IL-6-binding subunit. gp130-expressing cells were mainly CD34(+), suggesting that this receptor is expressed primarily by neovasculature endothelial cells. At the same time, a significant increase in phosphorylation of JAK2/STAT3 was observed in endothelial cells of stenotic AVFs. Interestingly, peripheral-blood mononuclear cells isolated at the time of AVF failure presented strikingly greater IL-6 expression compared with dialysis age-matched controls. IL-6 receptor activation may have a role in the pathogenesis of AVF failure in hemodialysis patients and may represent a potential therapeutic target in this setting.