Vascular brachytherapy for hemodialysis vascular access dysfunction: exploring an unmet clinical need.

Hemodialysis vascular access dysfunction is a major cause of morbidity and hospitalization in the hemodialysis population (230,000 patients in the United States) at a cost of well over 1 billion dollars per annum. Venous stenosis and thrombosis (due to venous neointimal hyperplasia), is the most common cause of hemodialysis vascular access dysfunction. At the clinical level, this manifests in the form of a 50%, one-year primary patency for new grafts, and a dismal 40% 3-month survival for thrombosed grafts. However, despite the magnitude of the clinical problem, there are currently no effective therapies for this condition. We and others have previously demonstrated that venous neointimal hyperplasia in polytetrafluoroethylene (PTFE) dialysis grafts is composed of smooth muscle cells/myofibroblasts, a perigraft macrophage layer and microvessels within the venous neointima. Interestingly, there is strong experimental evidence which demonstrates that radiation therapy blocks the proliferation and activation of all these cell types. In addition, endovascular radiation therapy has already been successfully used to prevent restenosis following coronary angioplasty. The BRAVO trial is a randomized, multi-center, double-blind clinical trial of endovascular radiation in PTFE dialysis grafts, sponsored by the Novoste Corporation. This trial is particularly significant as it is the first large multi-center study that is focused on testing a novel local intervention in the specific setting of dialysis access dysfunction. The rationale behind this study, and its design and the logistics involved, will also be described in this review.