2/29/2012

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Micah Chan MD MPH FACPClinical Chief, Division of Nephrology

University of Wisconsin School of Medicine and Public Health

New and Old Materials: Is This Important

For Graft Survival?ASDIN 8th Annual Scientific MeetingFebruary 24-26 2012

Outline

� Background

� Problem

� Studies

Background

� Vascular access dysfunction remains a major cause of morbidity and hospitalizations at a total cost of over $1 billion U.S. dollars annually (USRDS ADR 2010, FF Outcomes Dashboard v 1.4)

AVGs- A Snapshot in Time

Konner NDT 2005;20:2629, Scott Semin Vasc Surg 2007;20:158

The Problem

� Meta-analysis of 34 studies and 1245 AVGs showed primary patency of 58% and 33% at 6 months and 18 months respectively

� Secondary patency was 86% and 77% at 6 and 12 months(J Vasc Surg 2003;38:1005)

� USRDS DMMS Wave 2 of 1574 AVG, 492 simple AVF and 181 transposed AVF

� AVGs had a 41% greater risk of primary failure compared with simple fistulas (relative risk, 1.41; 95% CI, 1.22-1.64; P < .001) and a 91% higher incidence of revision (relative risk, 1.91; 95% CI, 1.60-2.28; P <.001).

� At 2 years, autogenous fistulas demonstrated superior primary patency (39.8% versus 24.6%, P < .001) and equivalent secondary patency (64.3% versus 59.5%, P = .24) compared with prosthetic grafts (J Vasc Surg 2001; 34:694)

The Problem

� In a review of 2300 cases of AVG venous stenoses, Beathard demonstrated the following distribution:

� 60% venous anastomosis

� 37% peripheral vein

� 38% within the graft

� 3% central veins

� 31% multiple locations

Beathard G. Semin Neph 2002; 22:202

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Polyurethane vs ePTFE

� 142 patients were randomized equally to receive one of the two grafts and were followed up prospectively to 12 months or to the end of secondary patency� Primary patency: PVAG 55% versus ePTFE 47% (6

months) and PVAG 44% versus ePTFE 36% (12 months) and secondary patency: PVAG 87% versus ePTFE 90% (6 months) and PVAG 78% versus ePTFE 80% (12 months). None of these differences were significant (P >.05).

� When time to first dialysis access was compared between the two grafts, 53.9% of all PVAG grafts were cannulated before 9 days versus none with the ePTFE grafts (P <.001)

Glickman MH et al J Vasc Surg 2001;34:465

Bovine mesenteric vein vs ePTFE

� Two-hundred seventy-six access grafts were implanted in patients who had at least one earlier failed synthetic graft. Of these grafts, 183 were MVB and 93 were synthetic. (ProCol graft, Hancock Jaffe, Irvine CA)� Primary patency at 12 months was 35.6% MVB versus

28.4% synthetic grafts.

� At 24 months, secondary patency was 60.3% MVB, 42.9% synthetic, and 18.0% INT (p < 0.0001, log- rank).

� Complication rates, including dilation, seroma, infection, and thrombosis, were all notably lower for the MVB compared with synthetic grafts by Cox regression (p < 0.001).

� Intervention rate per patient year was lower in the MVB group (0.97 versus 1.37) compared with synthetic grafts (p = 0.003).

Katzman HE et al J Am Coll 2005;201:223

Bovine carotid artery vs ePTFE

� 26 patients were randomized in the BCA group and 27 patients in the ePTFE group. (Artegraft, Inc. North Brunswick NJ)� There was no significant difference in secondary patency

rates

� Primary and assisted primary patency rates were significantly higher in BCA than in the ePTFE grafts (60.5% vs 10.1% and 60.5% vs 20.8% at 1 year, respectively)

� The BCA graft survival advantage was most profound in the upper arm grafts with significantly higher primary and assisted patency rates (P < .0001 and .0005, respectively)

� The total number of interventions (upper arm grafts) and total number of angioplasties (overall and upper arm) required to maintain patency were significantly fewer in the BCA group

Kennealey PT et al J Vasc Surg 2011;53: 1640

Cryopreserved fem vein grafts vs ePTFE

� Forty-eight cryopreserved femoral vein AVGs were placed in 44 patients. (CryoLife Inc. Kennesaw GA)� Thirty-eight (82%) of the cryopreserved femoral vein AVGs

were placed for infection, whereas the other 10 (18%) were placed for multiple graft failures with compromised venous outflow.

� 30 placed in upper arm, 8 in forearm, 8 in thigh and 2 elsewhere

� 1-year primary graft patency rate was 49% and the secondary graft patency rate was 75%.

� The 1-year primary and secondary patency rates for the prosthetic AVGs were 65 and 78%, respectively.

� In this study the overall patency rate of the cryopreserved femoral vein AVGs was similar to that for the PTFE AVGs (p = 0.519).

Matsuura J et al Ann Vasc Surg 2000;14:50

KDOQI guidelines

2.3 Dialysis AVGs:

2.3.1 The choice of synthetic or biological material should be based on the surgeon's experience and preference. The choice of synthetic or biological conduits should consider local experience, technical details, and cost. (B) 2.3.2 There is no convincing evidence to support tapered versus uniform tubes, externally supported versus unsupported grafts, thick- versus thin-walled configurations, or elastic versus nonelastic material. (A) 2.3.3 While the majority of past experience with prosthetic grafts has been with the use of PTFE, other prosthetics (eg, polyurethane [PU]) and biological conduits (bovine) have been used recently with similar outcomes. (B)

KDOQI 2006 Vascular access guidelines

Early Stick Graft (Nanovasc Inc,

Alameda CA)

Courtesy Nanovasc and Timmy Lee

JVA 2011;12:231

Biomaterial Platform Technology

– Biomimetic

– Hemocompatible

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Nanovasc: Improving Biocompatibility and Healing

Polymer solution

Capillary

Tip

Fiber

Formation

Fiber Mat

Counter Electrode

• Heparin bonded to

polyurethane

• Biomimetic and

hemocompatible surface

• Allows for endothelialization of

surface of graft

Heparin

PEG

Graft

• Electrospun polyurethane

Courtesy Nanovasc and Timmy Lee

JVA 2011;12:231

Nanovasc: Improving Biocompatibility and Healing

NanoVasc

ePTFE

SEM – CANNULATION SITE

Average Time to Hemostasis: 2:27 + 1:03

[min:sec]

Courtesy Nanovasc and Timmy Lee

JVA 2011;12:231

Early Clinical Data of NanoVasc Graft

14.3% @ 1 month

28.6% @ 3 months

42.9% @ 6 months

PERFORMANCE METRIC VS. PTFE

Dixon 2009 et al, NEJM

DAC Graft Study

Loss of Primary Patency

60% at 6 months77% at 12 months

10 patients from Nanovasc

Courtesy Nanovasc and Timmy Lee

JVA 2011;12:231

Summary Points

� Currently, there is insufficient evidence favoring a “new” vs “old” AVG type

� More intervention questions need to be asked and prospective randomized trials need to be done

� “In order to better understand the molecular basis for venous neointimal hyperplasia we need to develop a “back to basic science approach” with a focus on the genomic and proteomic analyses of stenotic tissue segments using both animal and human models.”

Yevzlin A, et al. Translational Research 2010;156;216, Lee T et al Adv Chronic Kidney Dis. 2009;16: 329

Thank You