Reducing Tunneled Dialysis Catheter Dysfunction through Nitric Oxide Release

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SUMMARY Tunneled Dialysis Catheters (TDCs) are an important mode of dialysis vascular access. 80% of incident dialysis patients begin hemodialysis with a TDC and the overall prevalence in the US is approximately 25%. Unfortunately, TDCs have huge problems with infection, thrombosis and central venous stenosis, which results in a very significant morbidity, mortality and economic cost. Despite the magnitude of the clinical problem, however, there are no effective therapies for TDC dysfunction. Nitric oxide (NO) is an important biological mediator, which has potent anti-bacterial, anti-platelet aggregation and anti-smooth muscle cell proliferation activities, which could potentially reduce TDC complications. We have previously developed a novel and innovative technology, to electrochemically modulate NO release (within a catheter lumen); in which a copper electrode embedded in a nitrite solution is able to generate NO (through the interaction between Cu ions and nitrite) over a prolonged period of time. The central hypothesis of this proposal, is that the electrochemically modulated release of NO from a lumen within a TDC could target all three major complications associated with TDC use (infection, thrombosis and central vein stenosis); thus significantly reducing the huge morbidity, mortality and economic cost associated with TDC use. We plan to address this central hypothesis through a series of specific aims that focus on (a) the development and validation (within a TDC lumen) of an electrochemically modulated NO release system with biological activity (b) reducing infection, thrombosis and central vein stenosis with NO releasing TDCs in-vivo, in a pig model. We believe that there is a huge unmet clinical need for novel therapies that reduce TDC dysfunction and feel that the concept of NO releasing TDCs could significantly reduce the huge clinical morbidity and economic cost associated with this intractable problem.