Preservation of Dialysis Access Patency

Vanderbilt University Medical Center, Nashville TN

Investigators

Abstract

? DESCRIPTION (provided by applicant): Hemodialysis is the primary lifeline for patients with end-stage renal disease (ESRD), but arteriovenous graft (AVG) failure imposes significant morbidity, mortality, and financial dispositions 1,2,3. Stenosis at the venous anastomosis ultimately leads to compromised blood flow, necessitating vascular interventions4-6. Failure rates of 50% after 1 year and 75% after 2 years are reported in hemodialysis patients that utilize polytetrafluoroethylene (PTFE) dialysis grafts1. There is currently no effective treatment to prevent this failure. However, external mesh supports applied in other settings, such as to saphenous vein grafts in heart or peripheral bypass grafting surgeries, have been shown to inhibit neointimal formation9-15. These materials have not been applied in the hemodialysis setting because of geometric complexities at the venous anastomosis. We will develop a mechanically compliant, moldable external support6 that can be custom fit around a dialysis graft anastomosis to prevent neointimal formation. This device will also provide localized, sustained delivery of therapeutics with anti-neointimal effects. A potent anti-neointimal peptide inhibitor, MK2i (Mitogen Activated Protein Kinase II), has demonstrated therapeutic potential in ex vivo human19 and in vivo mouse and rabbit vein interposition models22. We propose to use the moldable support system to deliver MK2i directly to the vein adventitia, thus maintaining higher drug concentrations with fewer toxicity concerns. Prevention of AVG failure in hemodialysis access patients represents an urgent, unmet clinical need. Amelioration of this problem would have a significant impact on clinical outcomes and economic repercussions of hemodialysis patients. This proposal offers a unique platform to advance adventitial drug delivery approaches and, if successful, could lead to therapeutic solutions in other clinical settings, such as coronary artery and peripheral bypass grafting surgeries.