AVF Prevalence. Local elastase to aid fistula maturation. I have nothing to disclose

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Julie Osborne
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Local elastase to aid fistula maturation Warren Gasper MD UCSF Vascular Surgery Fellow 2013 UCSF Vascular Symposium I have nothing to disclose AVF Prevalence 60.

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 60.6% (April 2012) 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 USRDS

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

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 ) 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 Maturation is a physiologic process Fixed Surgeon modifiable Co-morbidities associated with ESRD Age DM CAD, PAD 40-60% AVF maturation rate Experience >25 access cases Technique Anastomosis geometry Swing-segment handling Vein and artery diameter >2mm diameter artery >2.5mm diameter vein 10ml/min Immediate sequelae Low resistance arterial outflow Increased arterial and venous volume flow Increased shear stress leads to increased endothelial NO production and vasodilation 2

500ml/min 10ml/min 4-6 weeks 5 Intermediate and long-term changes MMP2/MMP9

smooth muscle, collagen, elastin content Sigovan et al, Ann Biomed Eng 2013 The

arteries that frequently contain medial calcifications Sigovan et al, Ann Biomed

3 500ml/min 10ml/min 4-6 weeks 5 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 Sigovan et al, Ann Biomed Eng 2013 Owens J Vasc Access 2011, Sorace J Ultrasound Med 2012, Allon Am J Kidney Dis

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 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 Peden J Vasc Access 2012 Factors associated with AVF maturation Fixed Co-morbidities associated with ESRD Age DM CAD, PAD Inflammation Impaired arterial dilation Surgeon modifiable Experience >25 access cases Technique Anastomosis geometry Swing-segment handling Vein and artery diameter >2mm diameter artery >2.5mm diameter vein 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

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 nonmaturation (95% CI) Estimated Sensitivity Estimated Specificity Radial artery diameter <2mm Cephalic vein diameter <2mm Intraoperative blood flow <170ml/min (radial) or <280ml/min (brachial) 1.5 (0.9 to 2.5) 38% 72% 1.9 (1.5 to 2.3) 38% 91% 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

KDOQI Guidelines. Overview. Predicting Successful Fistula Maturation Warren Gasper MD UCSF Vascular Surgery Fellow 2011 UCSF Vascular Symposium

KDOQI Guidelines. Overview. Predicting Successful Fistula Maturation Warren Gasper MD UCSF Vascular Surgery Fellow 2011 UCSF Vascular Symposium DISCLOSURES: NONE Predicting Successful Fistula Maturation Warren Gasper MD UCSF Vascular Surgery Fellow 2011 UCSF Vascular Symposium KDOQI Guidelines AV fistulas have better outcomes than grafts or catheters