Photodynamic Therapy to Prevent Arterio-Venous Fistula Maturation Failure: An Unmet Clinical Need Establishing and maintaining arteriovenous (AV) access sites is critical for patients on hemodialysis. The most preferred AV access is the forearm fistula which is now used for the majority of hemodialysis patients. However, a common problem with AV fistulas is primary maturation failure, i.e. following surgical placement, their fistulas do not become viable for dialysis without additional percutaneous or surgical interventions and some never become viable. This failure can lead to increased morbidity from prolonged use of central venous catheters and results in a large financial cost to the health care system. This is particularly frustrating because it is well established that a mature fistula provides the hemodialysis patient with the most effective means of AV access. While the exact mechanisms of maturation failure are not fully understood, it is generally accepted that post-surgical neointimal hyperplasia and inadequate venous remodeling play key roles and preventing either of these processes should substantially improve AV fistula outcomes. This project will investigate the potential for a particular form of photodynamic therapy to improve fistula maturation rates. Preliminary studies in related cardiovascular models indicate this therapy could substantially impact the main failure mechanisms involved in fistula maturation failure. From a commercialization perspective, this therapy also has the advantage that is already under late stage development in an unrelated disease indication, thus the typical drug development risks are substantially reduced. The project will be a joint effort between a commercial entity whose staff has extensive experience in vascular photodynamic therapy and a research partner who is a leader in AV access preclinical and clinical research. This Phase I project will focus on validating this therapy in an established preclinical model of AV fistula maturation failure. If this project is successful, it is envisioned that this technology should be suitable for initial clinical feasibility studies within the near term.
Public Health Relevance Statement: Project Narrative - Photodynamic Therapy to Prevent Arteriovenous Fistula Maturation Failure: An Unmet Clinical Need This projects aims to develop a therapy to substantially reduce the risk of arteriovenouos (AV) fistula failure in hemodialysis patients. Currently patients receiving such fistulas have primary failure rates as high as 60% resulting in the need for subsequent surgeries or percutaneous procedures that result in high added costs and extended periods of central catheter use which often results in associated morbidities. We envision that ultimate success in this effort could substantially reduce the costs and morbidities associated with AV access maintenance, an area where current medical expenditure in the US is estimated to be on the order of $5 billion.
Project Terms: Address; Anatomy; Aneurysm; Animals; Area; Arteriovenous fistula; Balloon Angioplasty; Bilateral; Biological; Biology; Blood flow; Blood Vessels; Caliber; Cardiovascular Models; Caring; Catheters; cell type; Clinical; Clinical Research; commercialization; Contralateral; cost; Development; Dialysis procedure; Disease; Dose; drug development; economic cost; effective therapy; End stage renal failure; Endothelium; Expenditure; experience; Extravasation; Failure; Family suidae; Feasibility Studies; Financial cost; Fistula; Forearm; Healthcare Systems; Hemodialysis; hemodynamics; Hemorrhage; Histologic; Hyperplasia; improved; Infection; infection risk; Inflammation; Inguinal region; Injury; innovation; innovative technologies; Innovative Therapy; Joints; Lead; Light; macrophage; Maintenance; Medical; Medicine; Microscopic; Modeling; Morbidity - disease rate; mortality; Myofibroblast; Names; Necrosis; novel; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Phase; Photosensitization; Photosensitizing Agents; Placebos; Play; Pre-Clinical Model; pre-clinical research; prevent; Procedures; Process; PUVA Photochemotherapy; Research; response; Risk; Safety; Short Waves; Signal Transduction; Singlet Oxygen; Site; Smooth Muscle Myocytes; Stenosis; Stents; success; systemic toxicity; Technology; Testing; Thrombosis; Time; Toxic effect; Treatment Efficacy; vascular injury; Venous
