1. SVS Clinical Research Priorities Hemodialysis Access
Thomas S. Huber, MD, PhD
Professor and Chief Division of Vascular Surgery
University of Florida College of Medicine

2. Patient Counts by Treatment for ESRD
ESRD is a tremendous public health problem – approximately 506,000 prevalent patients in 2006 with approximately 110,000 incident patients. Notably these numbers of increased three fold since Projected that there will be approximately 800,000 people by 2020

3. Prevalent Counts by Modality
65%
30%
Overwhelming majority the patients are on hemodialysis, transplant limited to 18,000/yr, wait on transplant is approximately 2 yrs 5%

4. 5-year Mortality by Incident Access
The 5 year mortality is contingent upon the incident mode of renal replacement therapy with those starting with a transplant 2.3 times more likely to survive 5 years compared to those on hemodialysis or peritoneal dialysis. 1 year mortality rate in the US for patients on hemodialysis is approximately 20%

5. Admission and LOS by Modality
Patients on either hemodialysis or peritoneal dialysis are admitted to the hospital an average of two times per year, while those with a transplant are admitted once. This accounts for an average of 14 hospital days for the dialysis patients and 7 hospital days for the transplant patients. The leading cause of admission is infection-related with the majority of these access-related.

6. Catheter Events and Complications
The annual access-related events and complications are highest for patients with catheters when compared to grafts and fistulas with an approximately 2 episodes/year for patients with catheters and < 1 episode/year in patients with grafts or fistulas

7. Fistula Events and Complications
The overall event and complication rates are lower for fistulas relative to grafts although the values are comparable.

8. Medicare Patients and Cost - 2006
The Medicare costs associated with ESRD are staggering. Although patients with ESRD account for only 1% of the Medicare population, they account for 7% of the cost

9. Medicare Expenditure – ESRD pt/yr
$77K
$72K
$53K
Among the hemodialysis patients, the greatest annual Medicare expenditure is for catheters - $77,000 catheters, $72,000 grafts, $53,000 fistulas

10. Need to understand evidence, opportunities, practice within the context of the national guidelines and initiatives that have shaped access care for the past decade and a half

11. Kidney Disease Outcomes Quality Initiative (KDOQI) – Access
NKF guidelines and practice recommendations.
Access guidelines – 1997, 2000, 2006.
Evidence-based approach.
Literature review.
Multidisciplinary work group.
THE GUIDELINES for access care.
KDOQI guidelines dealing not only with hemodialysis access but other components of care for patients with ESRD.

12. KDOQI – Overall Goals Increase use of AV fistula (autogenous).
Detect access dysfunction before thrombosis.
AVF > 65%, catheters < 10%.

13. KDOQI – Guidelines Patient preparation for permanent access.
Selection and placement of access.
Cannulation and accession.
Access dysfunction.

14. KDOQI – Guidelines Treatment of AV fistula complications.
Treatment of AV graft complications.
Treatment of catheter complications.
Clinical outcome goals.

15. SVS Clinical Practice Guidelines
Multidisciplinary group to optimize AV fistula.
Systematic review of evidence (external).
Timing of access referral.
Type of access.
Effectiveness of surveillance.
Published a

16. SVS Clinical Practice Guidelines
Timing of referral to access surgeon.
Strategies to optimize AV fistula.
First choice of access – forearm AV fistula.
Choice of access after forearm AV fistula.
Published a

17. SVS Clinical Practice Guidelines
Role of monitoring and surveillance.
Conversion of AV graft to AV fistula.
Management of non-functional access.
Published a

18. Fistula First Breakthrough Initiative (FFBI)
CMS multi-year initiative to increase AV fistula rates (2003 – 2006).
Multidisciplinary approach - ESRD networks.
KDOQI AV fistula goals
Initial – 50% incidence, 40% prevalence.
Updated – 66% prevalence by 2009.
Within the context of the KDOQI, FFBI was launched to help meet the KDOOQI guidelines
CMS – Centers for Medicare and Medicaid Services

19. Mission of FFBI Maximize AVF in all suitable patients.
Minimize dialysis catheter use.
Avoid all types of access complications.
A large percentage of the change concepts were aimed at surgeons
*Implemented through “Change Concepts”

20. FFBI
AVF
Total CVC
Total CVC

22. Limitations - Guidelines/Initiatives
Quality of the underlying evidence.
Outcomes may not be achievable.
Potential unintended consequences of emphasis on AV fistula.
Increased catheter use.
Increased AV fistula failure.
*New emphasis on “functional” access.

23. Randomized Trials and Meta-analyses
Preoperative strategies.
Ultrasound vein survey (benefit).
MR vs contrast venogram (comparable).
Intraoperative strategies.
Anticoagulation (no benefit).
Anesthesia –stellate block (benefit).
Staples vs suture (likely comparable).
Need transition – where do we stand, what is the evidence that went into the guidelines, what has been published since the guidelines, review of Medline, Cochrane, Clinical trials.gov for RCT and meta-analysis over the past decade, breakdown of publications

24. Randomized Trials and Meta-analyses
Selection of access type.
AVF vs prosthetic (AVF better).
Role of radiocephalic (high failure).
Radiocephalic vs forearm prosthetic.
Brachiobasilic vs prosthetic (BB better).
Brachiobasilic vs brachiocephalic (comparable).
Elderly patients (proximal access).
One vs two stage brachiobasilic (two stage better).

25. Randomized Trials and Meta-analyses
Choice of prosthetic/biologic graft.
Biologic vs PTFE (likely comparable).
PTFE vs PTFE (comparable).
Cuffed vs non-cuffed PTFE (cuff better).
PTFE vs TTFE (comparable).
Taper vs non taper PTFE (likely comparable).

26. Randomized Trials and Meta-analyses
Strategies to increase patency/decrease neointimal hyperplasia.
Medical.
Antiplatelet agents (no benefit).
Fish oil (no benefit).
Multiple others (unpublished or in progress).
Topical.
Paclitaxel (unpublished or in progress).
Radiation (no benefit).

27. Randomized Trials and Meta-analyses
Surveillance/remediation (potential benefit).
Ultrasound.
Flow.
Venous pressures.
Pre-emptive angioplasty.
Important area because of magnitude of problem, inherent expense, widespread of proliferation of access-centers, interventional nephrologists, Alan Lumsden – no benefit, Jack Work – no benefit

28. Randomized Trials and Meta-analyses
Management of complications.
Access thrombosis.
Open vs endovascular (open likely better).
Mechanical vs chemical (comparable).
Venous outflow stenosis.
Cutting balloons (no benefit).
Stents vs angioplasty (no benefit).
Covered stent vs angioplasty (covered better).
Covered stent vs non-covered (covered better).
Heparin-coated balloons (no benefit).

29. Limitations – RCT/Meta-analysis
Device/medication development trials.
Predominantly industry funding source.
Experimental design.
Small sample size.
Single center.

30. Dialysis Access Consortium (DAC)
NIDDK/NIH Consortium started in 2000.
Develop access clinical trials.
Role of pharmacologic agents.
Background of national AVF initiatives.
National institute of diabetes and digestive and kidney diseases, transition to NIH/NIDDI, highlight commitment to access, summarize trials and current direction, background of national initiatives – just need to create more fistulas or find a better surgeon

31. Emphasize multicenter, randomized trial, NIH/NIDDK support, JAMA publication
Dember JAMA 2008;299:2164

32. AVF/Clopidogrel - Hypothesis
Clopidogrel will reduce the occurrence of early AVF thrombosis and increase the proportion of new AVF that can be used for hemodialysis.

33. *Clopidogrel did not facilitate AVF maturation – 62% failure,
no difference in adverse events including bleeding.

34. Same study group, NEJM publication
Dixon NEJM 2009;360:2191.

35. AVG/DP/ASA - Hypothesis
DP/ASA can prevent stenosis and prolong survival of AVGs.

36. *no difference in cumulative patency, death, adverse outcome.
Median cumulative patency rate 22.5 mos

37. Identification of Factors Associated with Failure of Arteriovenous Fistulas to Mature in Hemodialysis Patients (U01)
Prospective multi-center observational cohort study investigating clinical factors predictive of and/or associated with failure of newly placed AVF to mature

38. Hemodialysis Fistula Maturation (HFM) Study Objectives
To identify predictors of AVF maturation.
To evaluate mechanisms of AVF maturation.
Domains - anatomy, biology , patient-specific attributes,
process of care 38

39. HFM Study Design
Prospective cohort study of 600 patients undergoing construction of AVF.
Participating centers
Clinical sites (Boston, Cincinnati, Utah, Florida, Washington, Texas-SW.
Cores (Histology, Ultrasound, Physiology).
Data coordinating (Cleveland Clinic). 39

40. HFM Outcome Measures Primary - unassisted clinical maturation
Use of the AVF with two needles for 75% of dialysis sessions within a 4-week period
Secondary – other maturation endpoints

41. HFM Unique Features Vascular physiological testing.
Attributes of clinical care.
Serial ultrasound measurements.
Stored blood and tissue samples.

42. Beauty of the HFM – validate/refute national target

43. Challenges/Specific Questions
AV fistula vs AV graft (specific scenarios).
Impact of comorbidities on access choice.
Access choice after failed forearm access.
Two stage vs one stage brachiobasilic.
Impact of graft modification on patency.
Multiple challenges/specific questions – forwarded along by the SVS membership

44. Challenges/Specific Questions
Role of surveillance and remediation.
Management of access complications.
Central vein stenoses.
Access-related hand ischemia
Venous outflow stenosis.
Thrombosed accesses.

45. Challenges/Specific Questions
Algorithm for “complex” access.
Impact of access on quality of life.
Development of catheter-free algorithms.
Optimal process of care

46. Low quality evidence from inconsistent studies with limited
protection against bias shows that autogenous access
for chronic hemodialysis is superior to prosthetic access.
J Vasc Surg 2008;48:34S.

47. Very low quality evidence yielding imprecise results
suggests a potentially beneficial effect of AV access
surveillance followed by interventions to restore
patency.
J Vasc Surg 2008;48:48S.

48. Proposed Research Emphasis
Develop a patient-centric, cost-effective algorithm for hemodialysis access.
Initial/subsequent access.
Strategies to facilitate AV fistula maturation.
Surveillance and remediation.
Management of complications.

49. Feasibility of Hemodialysis Access Trial
Significant problem with large patient population.
Low quality evidence with multiple questions.
National funding agency receptive.
Recognize magnitude of problem.
Commitment to clinical problem.
Ongoing discussion about next trial.
Potential for surgeon leadership.
*Key to identify “the” most compelling question.

50. Summary
Maintaining hemodialysis access is a tremendous public health problem in terms of the number of affected lives, associated morbidity/mortality and overall societal cost.
The national guidelines and initiatives have defined access care although the supporting evidence is limited.

51. Summary There are numerous outstanding access-related challenges.
The national funding climate appears receptive for an access-related trial.

52. Conclusion
The Society of Vascular Surgery should focus on end stage renal disease and develop a patient-centric, cost-effective algorithm for hemodialysis access.