Pathogensis and Local Drug Delivery for Prevention of Vascular Access Stenosis

A well-functioning vascular access is essential for hemodialysis in end-stage kidney disease patients. Synthetic grafts are more prone to the development of stenosis than native fistulas. Most of the stenosis is caused by neointimal hyperplasia localized at the outflow tract, which is perpetuated by continuous stimuli, such as blood flow disturbance, graft material bioincompatibility, and repeated needle puncture. Hyperplasia formation is also enhanced by the trauma of angioplasty. Recent work suggests that angiogenesis and the migration and proliferation of fibroblasts in the adventitia are important for the pathogenesis of neointimal hyperplasia. Therefore, the perivascular sustained delivery of antiproliferative drugs is a rational approach to inhibit hyperplasia associated with hemodialysis grafts. Because of the chronic nature of the stimuli, strategies that allow for the ready replenishment of the drug depot are preferable and are currently under development.