Although arteriovenous fistulae (AVFs) are the preferred mode of dialysis vascular access, over 50% fail to "mature" in that they do not develop an adequate blood flow or diameter to support hemodialysis. This results in a very significant clinical morbidity and economic cost. At a pathogenetic level, AVF maturation failure is due to (a) small vessels (b) "bad" hemodynamics that do not allow for the release of vasodilator molecules such as nitric oxide and (c) abnormal vascular biology due to uremia and oxidative stress. The central hypothesis for this proposal is that the placement of a malleable, coated (drug/cell/gene/chemical), biodegradable maturation enhancing stent (bMES) at the time of AV fistula creation will (a) dilate small veins (b) optimize anatomical configuration in order to improve hemodynamics and (c) improve upon "local" vascular biology as a result of the coated agents. We plan to address this central hypothesis through a series of specific aims that focus on (a) in-vivo degradation profile and toxicity for the bMES (b) in-vivo proof of principle experiments to document efficacy with regard to flow and diameter. We believe that there is a huge unmet clinical need for novel therapies that might enhance AV fistula maturation and that if successful, the concept of bMES could significantly reduce the huge clinical morbidity and economic cost associated with AVF maturation failure.
Although arteriovenous fistulae (AVFs) are the preferred mode of permanent dialysis vascular access, they have huge problems with non-maturation (failure to adequately increase flow and diameter to support dialysis). This proposal investigates the placement of a biodegradable maturation enhancing stent within the venous segment, which could significantly improve AVF maturation.
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