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      The Role of Shear Stress in Arteriovenous Fistula Maturation and Failure: A Systematic Review

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          Abstract

          Introduction

          Non-maturation and post-maturation venous stenosis are the primary causes of failure within arteriovenous fistulae (AVFs). Although the exact mechanisms triggering failure remain unclear, abnormal hemodynamic profiles are thought to mediate vascular remodelling and can adversely impact on fistula patency.

          Aim

          The review aims to clarify the role of shear stress on outward remodelling during maturation and evaluate the evidence supporting theories related to the localisation and development of intimal hyperplasia within AVFs.

          Methods

          A systematic review of studies comparing remodelling data with hemodynamic data obtained from computational fluid dynamics of AVFs during and after maturation was conducted.

          Results

          Outward remodelling occurred to reduce or normalise the level of shear stress over time in fistulae with a large radius of curvature (curved) whereas shear stress was found to augment over time in fistulae with a small radius of curvature (straight) coinciding with minimal to no increases in lumen area. Although this review highlighted that there is a growing body of evidence suggesting low and oscillating shear stress may stimulate the initiation and development of intimal medial thickening within AVFs. Further lines of evidence are needed to support the disturbed flow theory and outward remodelling findings before surgical configurations and treatment strategies are optimised to conform to them. This review highlighted that variation between the time of analysis, classification of IH, resolution of simulations, data processing techniques and omission of various shear stress metrics prevented forming pooling of data amongst studies.

          Conclusion

          Standardised measurements and data processing techniques are needed to comprehensively evaluate the relationship between shear stress and intimal medial thickening. Advances in image acquisition and flow quantifications coupled with the increasing prevalence of longitudinal studies commencing from fistula creation offer viable techniques and strategies to robustly evaluate the relationship between shear stress and remodelling during maturation and thereafter.

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          Most cited references51

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          EBPG on Vascular Access.

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            Molecular mechanisms in intimal hyperplasia.

            Intimal hyperplasia is the process by which the cell population increases within the innermost layer of the arterial wall, such as occurs physiologically during closure of the ductus arteriosus and during involution of the uterus. It also occurs pathologically in pulmonary hypertension, atherosclerosis, after angioplasty, in transplanted organs, and in vein grafts. The underlying causes of intimal hyperplasia are migration and proliferation of vascular smooth muscle cells provoked by injury, inflammation, and stretch. This review discusses, at a molecular level, both the final common pathways leading to smooth muscle migration and proliferation and their (patho)-physiological triggers. It emphasizes the key roles played by growth factors and extracellular matrix-degrading metalloproteinases, which act in concert to remodel the extracellular matrix and permit cell migration and proliferation. Copyright 2000 John Wiley & Sons, Ltd.
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              Why don't fistulas mature?

              Fistula maturation requires a compliant and responsive vasculature capable of dilating in response to the increased velocity of blood flowing into the newly created low-resistance circuit. Successful maturation to a high volume flow circuit capable of sustaining hemodialysis typically occurs within the first few weeks after creation. Failure to achieve maturation within 4-8 weeks should prompt a search for reversible etiologies; however, an accepted definition of maturation, particularly for patients not yet on dialysis remains elusive. The most commonly identified etiology is neointimal hyperplasia typically occurring in the juxta-anastomotic vein. However, failed maturation has also been reported secondary to impaired arterial and venous dilation and accessory veins. The exact frequency of each of these etiologies is unclear. Understanding the etiologies of impaired fistula maturation will focus future studies of targeted interventions to improve the rate of fistula maturation and increase the number of dialysis patients with a functioning autogenous fistula.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 December 2015
                2015
                : 10
                : 12
                : e0145795
                Affiliations
                [1 ]Centre for Applied Biomedical Engineering Research (CABER), Department of Mechanical, Aeronautical and Biomedical Engineering, Materials and Surface Science Institute, The Health Research Institute, University of Limerick, Limerick, Ireland
                [2 ]Department of Vascular Surgery, Limerick University Hospital, Dooradoyle, Limerick, Ireland
                [3 ]Department of Surgery, National University of Ireland, Galway, Ireland
                University of Washington, UNITED STATES
                Author notes

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

                Conceived and designed the experiments: LB KB PG EK SW MW. Performed the experiments: LB KB. Analyzed the data: LB KB PG EK SW MW. Contributed reagents/materials/analysis tools: PG EK SW MW. Wrote the paper: LB KB. Edited the manuscript: PG EK SW MW.

                Article
                PONE-D-15-24860
                10.1371/journal.pone.0145795
                4696682
                26716840
                e1af11b0-ed88-4ba8-b045-71915fc0350a
                © 2015 Browne et al

                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
                : 8 June 2015
                : 8 December 2015
                Page count
                Figures: 6, Tables: 8, Pages: 24
                Funding
                LB received funding from The Irish Research Council for Science Engineering and Technology (IRCSET). LB and MW received funding from The European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 324487.
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                Research Article
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                All relevant data are within the paper and its Supporting Information files.

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