AVF Prevalence 60.6% (April 2012) Fistula First Initiative - - PowerPoint PPT Presentation

4/20/2013 1

Local elastase to aid fistula maturation

Warren Gasper MD UCSF Vascular Surgery Fellow 2013 UCSF Vascular Symposium

I have nothing to disclose

AVF Prevalence

• Fistula First Initiative advocated for a 66%

prevalence of arteriovenous fistulas (AVF) for hemodialysis in hopes of reducing infection rates, lowering hospitalization rates, prolonging survival and reducing costs among ESRD patients

Vassalotti et al, Semin Dial 2012

60.6% (April 2012)

USRDS 2012

4/20/2013 2

AVF Prevalence

• A higher prevalence of AVFs for dialysis appears

to be associated with a reduction in hospitalizations due to access-related infections and a reduction in mortality

• However, 60-80% of patients initiate dialysis with

a central venous catheter (CVC)

• Conversion from CVC to AVF during the first year of

dialysis is associated with a significant reduction in mortality (adjusted HR 0.64, 95% CI 0.47-0.87)

• The morbidity and mortality of catheters appears to be

time-dependent

Bradbury et al Am J Kidney Dis 2009; USRDS 2012

Factors associated with AVF maturation

Fixed

• Co-morbidities

associated with ESRD

• Age
• DM
• CAD, PAD

Surgeon modifiable

• Experience
• >25 access cases
• Technique
• Anastomosis geometry
• Swing-segment handling
• Vein and artery

diameter

• >2mm diameter artery
• >2.5mm diameter vein

40-60% AVF maturation rate

10ml/min 50ml/min

Maturation is a physiologic process

Immediate sequelae

• Low resistance arterial outflow
• Increased arterial and venous

volume flow

• Increased shear stress leads to

increased endothelial NO production and vasodilation

4/20/2013 3

Sigovan et al, Ann Biomed Eng 2013

10ml/min 50ml/min 4-6 weeks ≥500ml/min 50ml/min ≥550ml/min Intermediate and long-term changes

• MMP2/MMP9 production
• Remodeling of artery and vein wall with alterations in

vascular smooth muscle, collagen, elastin content

Sigovan et al, Ann Biomed Eng 2013

The brachial artery

• Patients with

ESRD have stiff, poorly vasoreactive brachial arteries that frequently contain medial calcifications

Owens J Vasc Access 2011, Sorace J Ultrasound Med 2012, Allon Am J Kidney Dis. 2011

4/20/2013 4

Elastase: alter arterial behavior?

• Pancreatic elastase (PRT 201) applied to the

vessel adventitia cleaves elastin fibers

• Animal models of AVF have demonstrated

improved vessel dilation and increased blood flow with a reduction in neointimal hyperplasia and improvement in AVF patency rates after application of PRT 201

Peden J Vasc Access 2012

• Phase I/II dose finding trial of elastase (PRT 201)

applied to the anastomosis in 66 patients undergoing AVF

• No significant adverse events were associated

with PRT 201 use

• No difference in 1 year primary patency rates

Peden J Vasc Access 2012

Factors associated with AVF maturation

Fixed

• Co-morbidities

associated with ESRD

• Age
• DM
• CAD, PAD

Surgeon modifiable

• Experience
• >25 access cases
• Technique
• Anastomosis geometry
• Swing-segment handling
• Vein and artery

diameter

• >2mm diameter artery
• >2.5mm diameter vein

Inflammation Impaired arterial dilation

Conclusions

• AVF maturation is a dynamic physiologic process

that involves remodeling of both the artery and vein but current predictors are weak

• Technical factor such as minimum vein and artery

diameters and intraoperative blood flow are currently the best predictors of non-maturation

• “Traditional” cardiovascular risk factors poorly

predict maturation, but may be modifiable with novel therapeutics and a better understanding of AVF maturation biology and physiology

4/20/2013 5

Targeting the juxta-anastomotic segment

• Extra-vascular allogeneic

endothelial cells wrapped around juxta-anastomotic segment of AVF (n=31)

• Diabetics had significantly

less vein dilation at 24 weeks (-0.7mm vs 2.4mm, p<0.002)

• Diabetics treated with EC

matrix gel had more vein dilation at 24 weeks (+0.6mm vs -1.7mm, p=0.06)

JVS 2011

Systematic review of risk factors for fistula non-maturation

Relative risk of non- maturation (95% CI) Estimated Sensitivity Estimated Specificity

Radial artery diameter <2mm

1.5 (0.9 to 2.5) 38% 72%

Cephalic vein diameter <2mm

1.9 (1.5 to 2.3) 38% 91%

Intraoperative blood flow <170ml/min (radial) or <280ml/min (brachial)

3.5 (2.6 to 4.8) 50% 87%

• Standards for minimum vessel size and minimum

intraoperative blood flow have moderate specificity for fistula non-maturation, but poor sensitivity

JVS 2009