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      Thrombin-Anti-Thrombin Levels and Patency of Arterio-Venous Fistula in Patients Undergoing Haemodialysis Compared to Healthy Volunteers: A Prospective Analysis

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          Abstract

          Background

          Patients on haemodialysis (HD) are at an increased risk of sustaining thrombotic events especially to their vascular access which is essential for maintenance of HD.

          Objectives

          To assess whether 1) markers of coagulation, fibrinolysis or endothelial activation are increased in patients on HD compared to controls and 2) if measurement of any of these factors could help to identify patients at increased risk of arteriovenous (AVF) access occlusion.

          Patients/Methods

          Venous blood samples were taken from 70 patients immediately before a session of HD and from 78 resting healthy volunteers. Thrombin-antithrombin (TAT), D-dimer, von Willebrand factor (vWF), plasminogen activator inhibitor-1 antigen (PAI-1) and soluble p-selectin were measured by ELISA. C-reactive protein (hsCRP) was measured by an immunonephelometric kinetic assay. Determination of the patency of the AVF was based upon international standards and was prospectively followed up for a minimum of four years or until the AVF was non-functioning.

          Results

          A total of 70 patients were studied with a median follow-up of 740 days (range 72-1788 days). TAT, D-dimer, vWF, p-selectin and hsCRP were elevated in patients on HD compared with controls. At one year follow-up, primary patency was 66% (46 patients). In multivariate analysis TAT was inversely associated with primary assisted patency ( r= -0.250, p= 0.044) and secondary patency ( r = -0.267, p= 0.031).

          Conclusions

          The novel finding of this study is that in patients on haemodialysis, TAT levels were increased and inversely correlated with primary assisted patency and secondary patency. Further evaluation is required into the possible role of TAT as a biomarker of AVF occlusion.

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          Most cited references37

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          Recommended standards for reports dealing with arteriovenous hemodialysis accesses.

          The incidence rate of treated end-stage renal disease in the united states is 180 per million and continues to rise at a rate of 7.8% per year. Arteriovenous hemodialysis access (AV access) creation and maintenance are two of the most difficult issues associated with the management of patients on hemodialysis. The 1-year complication rate of a primary prosthetic AV access for hemodialysis ranges from 33% to 99%. Various investigators report on patency and complications of AV access. However, it is rather difficult to compare outcomes because of the wide variety of access materials, configurations, locations, risk factors, and quality of inflow and outflow vessels. Although there have been reporting standards for dialysis access endovascular interventions and for central venous access placement, standards regarding surgical access placement and its revision are lacking. The "Dialysis Outcome Quality Initiative," published by the National Kidney Foundation, provides recommendations for optimal clinical practices aimed at improving dialysis outcome and patient survival. This reporting standards document is not meant to be a "practice guidelines" or "best practices" document. Rather, the purpose of this document is to provide standardized definitions related to AV access procedures and to recommend reporting standards for patency and complications, to be used by surgeons, nephrologists, and interventional radiologists, that will permit meaningful comparisons among AV access procedures. The terms, definitions, and categories featured in this article have been approved by the Committee on Reporting Standards of the Society for Vascular Surgery and the American Association for Vascular Surgery and should be observed in preparing manuscripts on AV accesses for submission to the Journal Of Vascular Surgery.
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            C-reactive protein is a mediator of cardiovascular disease.

            C-reactive protein is postulated to embody an index that can reflect cardiovascular risk and can be used to independently predict major cardiovascular events and mortality. On the other hand, credible experimental data have become available that demonstrate the abundant presence of C-reactive protein in atherosclerotic lesions and, moreover, identify C-reactive protein as an initiator of several pathogenic pathways that can cause atherogenic changes. Consequently, there has been a paradigm shift in which C-reactive protein is no longer regarded as merely an indicator of cardiovascular risk, but increasingly considered a direct partaker in the pathogenesis of atherosclerotic cardiovascular disease. These data underscore the need to explore risk-reducing interventions that selectively inhibit C-reactive protein activity as a novel strategy to prevent clinical manifestations of atherosclerosis.
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              Hemodialysis arteriovenous fistula patency revisited: results of a prospective, multicenter initiative.

              Vascular access standards are predominantly based on older, single-center reports; however, the hemodialysis population has changed dramatically and primary arteriovenous fistula failure is a huge problem. This prospective, multicenter study used standardized definitions to analyze patency rates and potential risk factors that affect functional patency and late arteriovenous fistula functionality. Eleven centers participated in a guidelines implementation program. All new permanent vascular accesses were included. Patency and functional patency, defined as access survival from creation and from first dialysis use, respectively, were calculated using Kaplan-Meier analysis. Risk factors for primary functional patency loss (intervention-free interval) and secondary failure (abandonment) were determined using regression models. A total of 491 arteriovenous fistulas were placed in 395 patients. Six-, 12-, and 18-mo secondary patency and functional patency were 75 +/- 2.0, 70 +/- 2.3, and 67 +/- 2.7% and 90 +/- 1.9, 88 +/- 2.2, and 86 +/- 2.7%, respectively. Primary failure rate was 40%. Thrombosis rate was 0.14 per patient-year. Diabetes and arteriovenous fistula surveillance were significantly associated with primary functional patency loss. Preoperative duplex was inversely related to secondary failure. The secondary failure rate per hospital varied from 0 to 39%. This study showed a marked difference between patency and functional patency, likely to be explained by high primary failure rates. Hemodialysis patients with diabetes can be expected to have reduced primary functional patency rates, but if treated adequately, then arteriovenous fistula functionality can be maintained as long as in patients without diabetes.

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                2 July 2013
                : 8
                : 7
                : e67799
                Affiliations
                [1 ]Department of Vascular Surgery, Aberdeen Royal Infirmary, Aberdeen, Scotland
                [2 ]Division of Applied Medicine, University of Aberdeen, Aberdeen, Scotland
                [3 ]Renal Medicine, Aberdeen Royal Infirmary, Aberdeen, Scotland
                Institut National de la Santé et de la Recherche Médicale, France
                Author notes
                * E-mail: j.milburn@nhs.net

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JM IF NJM NF JB. Performed the experiments: JM IF NJM. Analyzed the data: JM IF NJM JB. Contributed reagents/materials/analysis tools: IF NJM NF. Wrote the manuscript: JM IF NJM NF JB.

                Article
                PONE-D-13-03656
                10.1371/journal.pone.0067799
                3699493
                23844096
                41e447cc-d4d4-4304-8679-489d72e64299
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 January 2013
                : 27 May 2013
                Funding
                This project was funded by the Grampian Renal Research Fund. N.J.M. was supported by the British Heart Foundation (FS/11/02/28579). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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