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.