Sirolimus-loaded polyurethane graft for hemodialysis access in sheep

Intimal hyperplasia is the most common final pathway for hemoaccess occlusion in dialysis patients. Drug eluting stents have been shown to decrease intimal hyperplasia in coronary arteries and possibly in peripheral arteries. We evaluated the use of a sirolimus loaded polyurethane graft as prophylaxis in hemodialysis access. Grafts were loaded with sirolimus and elution curves were determined for the polyurethane material. The arteriovenous grafts were then placed in the neck of 20 sheep. A non-loaded graft was placed in the contralateral neck. Patency rates, ultrasound evaluation, angiography and histomorphometry were determined for each graft. At 30, 60 and 90 days the drug loaded graft had improved patency rates compared to the control, with a 25% improvement noted at 3 months. Life table analysis showed the drug loaded graft consistently better patency than the control (p=.136). The control graft had greater neointimal stenosis (14.5% vs. 9.17%) over the course of the study (p=.157). Although none of these findings was statistically significant in this pilot study, the sirolimus coated graft out-performed the control in every measured parameter at each time point evaluated. Further work to asses the validity of drug coated materials to prevent intimal hyperplasia in hemodialysis access is warranted.