Access Flow Based Intervention for Management of Arteriovenous Hemodialysis Access Dysfunction.
Access Flow Based Intervention for Management of Arteriovenous Hemodialysis Access Dysfunction.
Hemodialysis (HD) vascular access dysfunction is a huge clinical problem which results in
 significant clinical morbidity in patients with End Stage Renal Disease (ESRD), causing a
 severe economic burden on any health care system. Arteriovenous (A-V) dialysis accesses are
 the preferred form of permanent dialysis access as compared to central venous catheters (CVC)
 . One of the reasons for CVC use is poor long term patency rates of A-V access. Arteriovenous
 Grafts (AVG) have a primary patency rates of just under 50% at 12 months and around 33% at 18
 months. Native arteriovenous fistula (AVF) are slightly better with primary patency rates of
 around 60 percent at one year and 51 percent at 2 years. The most common cause for AVF and
 AVG dysfunction is stenosis development due to neointimal hyperplasia (NIH) within the
 circuit leading to access thrombosis. Percutaneous transluminal angioplasty (PTA) is the
 current standard of treatment for these lesions. Despite being the treatment of choice for
 these lesions patency rates after PTA continue to be dismal. One of the problems with poor
 long term outcomes after successful intervention is how you assess immediate intervention
 success. Successful angioplasty is defined by Dialysis Outcome Quality Initiative (DOQI)
 guidelines as one where only less than 30% residual stenosis remains at the end of
 intervention. Unfortunately angiographic images post angioplasty correlate poorly with
 improvement of access flows through the arteriovenous circuit. There are two main problems
 with these practice standards. First, they are based on a 2-dimensional angiographic view of
 the lesion which may be misleading. Secondly, this assessment of recoil is very subjective
 and not base on objective data.

 Access flow monitoring can now be performed intra-procedurally with thermal dilution
 technique. Its benefit was shown in a small pilot study. To date there have not been any
 randomized controlled trials to assess the benefit of such an approach where intervention is
 based on improvements in access flow at the time of intervention. We hypothesize that such an
 approach will improve outcomes after interventions related to access dysfunction. This may
 also identify the right scenarios in which stent placement may benefit thus improving
 outcomes after stent placement as well.
Background:

 The number of patients with End Stage Renal Disease (ESRD) requiring renal replacement
 therapy (RRT) in the form of dialysis is on the rise. Hemodialysis (HD) remains the most
 prevalent form of RRT for patients with ESRD. Just in the United States there are more than
 350,000 patients with ESRD on hemodialysis (HD) and the number is expected to increase to
 500,000 by the year 2023. Recent data provided by Saudi Centre for Organ Transplantation
 shows that there are just over 13000 patients with ESRD on hemodialysis in the Kingdom of
 Saudi Arabia (KSA). This number is expected to rise at a rate of 7-8% annually reaching 18000
 by year 2018. Establishing a viable vascular access is crucial and is considered the
 'life-line' for such patients.

 HD vascular access dysfunction is a huge clinical problem which results in significant
 clinical morbidity in patients with ESRD, causing a severe economic burden on any health care
 system. In the United States <50% of all hemodialysis accesses remain patent at 3 years with
 the economic burden of maintaining vascular access patency calculated to exceed $1 billion
 annually. Arteriovenous (A-V) dialysis accesses are the preferred form of permanent dialysis
 access as compared to central venous catheters (CVC) due to less complications and better
 patient outcomes. Native arteriovenous fistulae (AVF) and synthetic arteriovenous grafts
 (AVG) are the two main types of A-V access used for HD. Despite the obvious benefits many
 patients on HD continue to dialyze with CVC as there dialysis access. One of the reasons for
 CVC use is poor long term patency rates of A-V access. AVG have a primary patency rates of
 just under 50% at 12 months and around 33% at 18 months. AVF are slightly better with primary
 patency rates of around 60 percent at one year and 51 percent at 2 years. The most common
 cause for AVF and AVG dysfunction is stenosis development due to neointimal hyperplasia (NIH)
 within the circuit leading to access thrombosis. Percutaneous transluminal angioplasty (PTA)
 is the current standard of treatment for these lesions. Despite being the treatment of choice
 for these lesions patency rates after PTA continue to be dismal. Long-term success rates are
 generally listed as either primary/unassisted rates (patency without additional procedures))
 or secondary/assisted patency (patency with additional procedures). Unassisted patency rates
 for angioplasty generally range from 41 to 76 percent at six months and 31 to 45 percent at
 one year. To improve the primary patency after intervention many strategies have been looked
 at. Placement of covered stents at the time of intervention has been used, but patency rates
 after stent placements although better than PTA, are still not optimal. One of the problems
 with poor long term outcomes after successful intervention is how you assess immediate
 intervention success. Successful angioplasty is defined by Dialysis Outcome Quality
 Initiative (DOQI) guidelines as one where less than 30% residual stenosis remains at the end
 of intervention. It is suggested that if residual stenosis is >30% after angioplasty with
 adequately sized fully effaced angioplasty balloon than stent placement should be considered.
 Unfortunately angiographic images post angioplasty correlate poorly with improvement of
 access flows through the arteriovenous circuit. There are two main problems with these
 practice standards. First, this is based on a 2-dimensional angiographic view of the lesion
 which may be misleading. Secondly, this assessment of recoil is very subjective and not base
 on objective data.

 Surveillance of AV access with access flow monitoring is recommended to identify AV access
 with stenosis before they develop thrombosis. One of the methods most commonly used to assess
 access flows is ultrasound dilution technique. This can be performed at the time of dialysis
 by trained staff to assess access flows. Access flow measurements are usually done monthly in
 units who have access surveillance programs in place. It has been shown that improvement in
 access flows after intervention from baseline or pre intervention values can predict long
 term outcomes after intervention. Although helpful, but access flows are performed at HD unit
 on the following days after the patient had intervention. At that time it is impractical to
 bring the patient back for intervention and leads to additional cost and inconvenience. As
 such the clinical benefit of this approach is minimal. In addition many dialysis units do not
 have access flow measurement available and no surveillance programs implemented.
 Unfortunately this is true for most hemodialysis units in the Kingdom of Saudi Arabia (KSA).
 Fortunately access flow monitoring can now be performed intra-procedurally with the same
 ultrasound dilution technique. Its benefit was shown in a small pilot study. To date there
 have not been any randomized controlled trials to assess the benefit of such an approach
 where intervention is based on improvements in access flow at the time of intervention. The
 researchers hypothesize that such an approach will improve outcomes after interventions
 related to access dysfunction. This may also identify the right scenarios in which stent
 placement may benefit thus improving outcomes after stent placement as well. This approach
 should also improve outcomes and reduce repeat hospital visits in areas where access flow
 monitoring at HD units is not readily available as is the case in most centers in the Kingdom
 of Saudi Arabia.

 Specific Aims In a randomized, controlled, blinded trial the researchers would like to assess
 the clinical utility of an access flow based intervention approach as compared to
 conventional approach for managing dialysis arteriovenous access dysfunction.

 Materials and Methods

 A. Study Design:

 Prospective, Randomized Controlled, single centre trial comparing access flow based
 intervention versus conventional standard approach for dialysis access dysfunction.

 B. Study Subjects ESRD patients on HD referred for access dysfunction to the interventional
 nephrology service at King Faisal Specialist Hospital and Research Center in Riyadh, KSA.

 Sample Size:

 116 patients are required to have an 80% chance of detecting, at significance level of 5%, an
 increase in the primary patency outcome measure from 45% in the control group to 70% in the
 experimental group at 6 months meaning 58 patients in each arm. The researchers plan to
 enroll a total of 140 patients with 70 in each group.

 Data Collection:

 Patient Demographics:

 Age Sex ESRD or Chronic Kidney Disease stage 5 needing HD Currently on Dialysis Y N

 If yes: currently used access type:

 Years on Dialysis:

 Diabetes Mellitus Hypertension Peripheral Vascular Disease Smoking Coronary artery disease
 Cerebrovascular accidents Antiplatelet medications

 Location of AVF:

 Location of AVG:

 Reason for procedure: Excessive bleeding post HD Low Access flows High venous or low arterial
 pressures Physical Examination abnormality Other

 Pre-procedure within 3 month baseline access flows known Y N

 If known, Value:

 Data on 1st Angiogram:

 Stenosis present: Y N If yes: Location of Stenosis: Arterial Juxta anastomosis Arterial 1/3rd
 Middle 1/3rd Venous 1/3rd or venous outflow

 Pre-intervention access flow in case of no thrombosis (A):

 Targeted access flow:

 Stenosis successfully treated radiologically Y N Targeted access flow successfully reached: Y
 N

 Post-intervention access flow (B):

 Percentage access flow reached of target (B/A x 100):

 Residual Stenosis in %:

 By Operator By Blinded Interpreter:

 Max diameter of balloon used:

 Max inflation pressure of balloon used:

 Stent used: Y N

 If used, size of stent: # of stent:

 Follow up:

 Access Flows:

 Within 1st three treatments post intervention 3rd month 6th month

 Physical Examination abnormalities if any:

 3rd month 6th month

 Time to first intervention after initial procedure:

 If intervention, reason for the need of intervention:

 Primary patency at 6 months: Y N

 If no, exact duration of primary patency:

 Secondary patency at 6 months: Y N

 Statistical Considerations:

 The researchers will use block-randomization for the recruited subjects into the two arms.
 Researchers will take the risk difference as an effect measure. The chi-square test will be
 used to assess the superiority of the new treatment as compared to the standard protocol.
 Researchers will set the type I error rate at 5%. Baseline comparisons between the two groups
 will be conducted using the two independent samples t-test for continuous data which will be
 summarized as means ± standard deviation, and using the chi-square test for categorical data.

 Ethical Considerations / Consent Documents The proposal of this study has been approved by
 the local review authority which is the Office of Research Affairs at King Faisal Specialist
 Hospital and Research Centre.

 All participants will be assigned serial numbers in order of data collection. Each medical
 record number will be assigned a specific serial number and this list will be kept in the
 PI's office. All investigators mentioned in the study will have access to them. Databases
 created will be password protected.

 The study will be managed by the PI in cooperation with other Co-Investigators
Inclusion Criteria:

 -  Age >18 years

 -  Patients with ESRD and access dysfunction secondary to stenosis anywhere in the AVF.

 Exclusion Criteria:

 -  Patients on anti-coagulation and those with bleeding disorders

 -  Life expectancy less than 12 months.

 -  Documented severe contrast allergy.

 -  Inability to come for timely and adequate follow up.

 -  Patients undergoing transplantation work up and expected to be transplanted within 6
 months.

 -  AVG with access dysfunction developing within 30 days of surgery.

 -  AVF with early fistula failure.

 -  Recurrence of stenosis within 3 months of previous intervention.