Currently, in the United States, there are approximately 425,000 patients receiving hemodialysis (HD) and it is estimated that 30-60% of this population have some element of hand dysfunction after hemoaccess surgery. The spectrum of hand disability that HD patients present with includes subtle fine neuromotor discoordination, paresthesia, pain, paraparesis and digital gangrene. The underlying pathophysiologic mechanisms responsible for this problem are poorly understood. More than 80% of patients have significant perturbations in hemodynamic variables such as wrist and digit pressures; however, these differences poorly correlate with changes in hand function. This heterogeneity in the clinical phenotype suggests that factors other than hand perfusion regulate development of hand dysfunction after arteriovenous fistula surgery.

The renal dysfunction milieu causes a variety of physiologic derangements in HD patients including increased oxidative stress and chronic inflammation that have been implicated as major contributors to accelerated atherosclerosis and elevated mortality. The central hypothesis of the proposed study is that renal dysfunction alters baseline mitochondrial function in skeletal muscle and neuromuscular junction, but the magnitude of this change is insufficient to lead to the clinical phenotype (i.e. altered hand function). I will focus on determining if global and/or mitochondrial-targeted antioxidant therapies can improve neuromuscular function and reduce pathology following AVF placement in mice.