Development of an infection-resistant Hemodialysis access graft
Summary
Background:
End Stage Renal Disease (ESRD) is a chronic condition best treated with a kidney transplant, but due to the limited availability of transplantable organs, most patients end up on dialysis, most commonly hemodialysis (HD). According to the United States Renal Data System (USRDS), the number of people on dialysis in the US in 2018 was over 785,883 and is increasing every year. Every one of these patients will need dialysis access placed, with one of the most common hemodialysis access being creation of an arteriovenous (AV) graft.
Problem:
The problem with hemodialysis access grafts is that they commonly fail, often due to infection, and graft failure directly decreases survival. Only 58% of AV grafts are patent after 6 months. Additionally, 48 to 73% of all bacteremia in HD patients are caused by infection of the hemodialysis access, particularly the prosthetic AV graft composed of polytetrafluorotethylene (PTFE). Infection in AV grafts is usually due to Gram-positive bacteria, in particular, Staphylococcus aureus is documented in as many as 68% of infections. The current practice of using antibiotics or antimicrobials for infection management is ineffective at preventing infection and increases risk for the development of bacterial resistance. To address this concern, projects have focused on prevention of graft thrombosis due to neointimal hyperplasia at the AV graft outflow and prevention of infection. Despite that, there is currently no complete system of dialysis access graft that covers patency, infection resistance and bacteremia prevention.
Project Goal:
Using our unique team of researchers, we plan to create a comprehensive AV access graft to improve patency and decrease infections in ESRD patients. The project aims to:
- Create an optimized microbial resistant conduit for AV graft creation
- Determine a long-term strategy for hemodialysis access to minimize bacterial contamination of the prosthetic graft
Specific Aims:
Aim 1: Design and fabricate an AV access graft with long term patency and infection resistance
Aim 2: Assess the adherence of S. aureus to optimize graft resistance to bacterial colonization, formation of biofilm and infection under flow conditions and by comparison to alternative grafts currently in clinical use.
Aim 3: Perform in vivo studies to assess graft patency and resistance to infection compared to current clinical grafts
Commercialization Plan:
Intellectual Property: The UAMS Bioventures is in the process of filing a provisional patent application for a platform technology which can be developed for Hemodialysis AV graft.
Milestones: We would design and fabricate functional Av access graft prototypes that we would use for bench testing and animal studies. After completion of toxicology studies and will provide full GMP-grade material suitable for regulatory studies and Phase I trials. We will be applying for an SBIR grant, along with the Arkansas Matching Grant. These funding sources will help us satisfy the costs associated with animal testing, manufacturing, and regulatory approval. We will then seek SBIR phase two grant and other financing to get through clinical trials to product deployment.