|Principal Investigator: Alfred Cheung|
|Keywords: Hemodialysis , Fistula maturation , dialysis access , hemodynamics , wall shear stress , magnetic resonance imaging||Department: Nephrology|
|IRB Number: 00049099||Co Investigator: Christi Terry|
|Specialty: Vascular Surgery|
|Recruitment Status: Completed|
The goal of the study is to examine how blood flow patterns in the developing fistula influence fistula maturation. Although the patterns and intensity of blood flow through blood vessels is known to impact vessel remodeling and development of blood clots, overgrowth of vascular tissue and other diseases, the relationship of blood flow in the developing fistula and later fistula failure or success is currently not known.
SPECIFIC AIMSThe parent NIDDK-sponsored Hemodialysis Fistula Maturation (HFM) cohort study will study the relationshipsof a broad range of clinical, physiological, and process-of-care variables with maturation and usability fordialysis of newly-placed arteriovenous fistulas (AVF). We propose a highly synergistic ancillary study to obtainmechanistic insights into the pathobiology of AVF failure by examining the interplay of hemodynamic wall shearstress (WSS) in the AVF with pre-existing vascular properties, in influencing AVF maturation.Hypotheses(1) Hemodynamic WSS at the venous wall is a crucial determinant of AVF development (specifically, lumencross-sectional area and blood flow rate).(2) The effect of WSS on wall remodeling is modulated by local pre-existing endothelial functionality, vein wallmorphometry, and venous biomechanics.Specific Aim 1: To monitor the lumen geometry and blood flow rate of newly-created AVFs over time, anddelineate WSS profiles from these structural and flow rate data.Approach: Magnetic resonance imaging (MRI) will be performed at 2 days, 6 weeks, 6 months and 18 monthspost-operatively. At each time point, the entire lumen geometry and the blood flow rates at strategic locationswill be obtained by contrast-free MRI, and WSS profiles in the AVF will be derived from these MRI data usingcomputational fluid dynamic (CFD) modeling.Specific Aim 2: To describe the relationships of local WSS parameters soon after AVF creation (e.g., 2 days, 6weeks) to changes in AVF lumen cross-sectional area and blood flow rate in the succeeding periods.Approach: A panel of local WSS parameters (time-averaged WSS, peak WSS, spatial WSS gradient andoscillatory shear index (OSI)) will be derived from CFD modeling at increments along the length of the AVF.The associations of 2-day WSS parameters with subsequent changes in lumen area and blood flow rate at thesame location at 6 weeks will be examined. Analogously, the associations of 6-week WSS parameters withsubsequent changes in lumen area and blood flow rate will also be studied.Specific Aim 3: To assess pre-existing endothelial functionality, vein wall morphometry and venousbiomechanics as additional predictors, confounders, or especially modifiers of the relationships between WSSparameters and subsequent changes in AVF lumen area and blood flow rate studied in Aim 2.Approach: Results of the following standardized testing in the parent study will be used: (a) pre-operativebrachial artery flow-mediated dilation (FMD); (b) pre-operative forearm venous plethysmography (VP); and (c)morphometry from a vein segment collected intra-operatively. Statistical models will be used to study the interrelationshipsamong these variables in predicting subsequent changes in AVF lumen cross-sectional area andblood flow rate, with particular attention to altered relationships of WSS parameters with subsequentmaturation, as a result of FMD, venous plethysmography, or vein morphometry abnormalities in the patients.The proposed studies will effectively exploit the unique data collection effort in the parent HFM study(“Vascular Wall Biology” in Fig. 1), add significantmechanistic insight into the physiology andpathophysiology of AVF development, and increasethe understanding of the role of hemodynamic factorsin determining the substantial heterogeneity in AVFmaturation. We anticipate that non-physiologicalvenous flow (e.g., very high and very low WSS, highspatial WSS gradient, and high oscillatory shearindex) at an earlier time point will be associated with afailure of the AVF to mature. Specifically, we postulatethat vein wall that experiences non-physiological flow patterns will have a lack of outward wall remodeling andundergo the development of neointimal hyperplasia and stenosis at those regions at a later time point, limitingthe blood flow rate and lumen dilation of the AVF. Clinically, these results will provide important insights thatcan be used to optimize anatomical configuration and surgical techniques used in AVF creation, and contributeto earlier post-operative identification of AVFs that are prone to maturation failure.
Both female and male participants undergoing elective surgery for AVF creation for hemodialysis.
• Planned creation of an autogenous upper-extremity AVF by a surgeon participating in the study
• Currently on chronic dialysis, or expected to be started on chronic dialysis within three months of the planned AVF creation surgery
• Age allowing legal consent without parental involvement which is 18 years of age or older in the State of Utah
• Life expectancy ≥ nine months
• Ability to give informed consent
• Anticipated ability to meet all study protocol requirements.
- Patients with metal implants or claustrophobia will be excluded from this ancillary study because of the MRI scans. Metal implants include, but are not limited to, newly-placed vascular stent, cardiac pacemaker and cochlear implant.
- Pregnant women will be excluded from the study. No effects on the fetus have been shown to occur with MRI. Unlike with x-rays or computed tomography (CT) scans, MRI does not use ionizing radiation. However, current guidelines recommend that pregnant women undergo MRI procedures only when essential, thus pregnant patients are excluded from this study.
If you finish the whole study, the compensation you will receive will not exceed $375.00.