# Impaired Mitochondrial Energetics is a Driver of Hemodialysis Access Related Hand Dysfunction > **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $515,943 ## Abstract PROJECT SUMMARY Currently, in the United States, there are ~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 underlying pathophysiologic mechanisms responsible for this devastating problem are poorly understood. The renal dysfunction (RD) milieu causes a variety of physiologic derangements in HD patients including increased oxidative stress (OS) and chronic inflammation that have been implicated as major contributors to accelerated atherosclerosis and elevated mortality. Profound changes in OS contribute to skeletal muscle and neuromuscular junction dysfunction associated with muscle atrophy and frailty in this population. AVF surgery causes significant hemodynamic changes in the extremity which presents an adaptive challenge to the skeletal muscle and neuromotor end-plate. Supported by our previous work, as well as preliminary data on RD associated skeletal muscle mitochondrial phenotypic changes, we propose that RD driven mitochondrial dysfunction alters skeletal muscle and neuromuscular junction responses to AVF induced ischemia leading to clinically apparent hand dysfunction. Further, these pathways can be modified either prior to AVF creation or at first evidence of hand dysfunction to reverse/prevent the functional impairment. Our hypothesis is that the RD milieu disrupts mitochondrial and cellular energetics resulting in elevated OS predisposing patients undergoing AVF surgery to developing skeletal muscle and neuromuscular junction perturbations causing clinically significant hand dysfunction. RD mediated mitochondrial impairments are further exacerbated by local hemodynamic changes following AVF creation through maladaptive OS metabolic responses that drives the diversity of clinically apparent hand dysfunction. Aim 1 will establish how RD impacts mitochondrial and cellular energetics that are exacerbated by AVF-induced limb ischemia. Using a series of in vitro experiments, we will uncover the biochemical mechanisms by which RD impacts mitochondrial energetics leading to impaired oxidative phosphorylation and increased OS. Aim 2 will determine the efficacy of global or mitochondrial-targeted antioxidant therapies delivered prior to- and following AVF surgery in mice. Using a novel RD murine AVF model, we will determine whether global (N-acetylcysteine) or mitochondrial-targeted (AAV delivery of mitochondrial targeted catalase) antioxidant therapy have therapeutic potential for AVF-induced muscle dysfunction. Aim 3 will evaluate the association between mitochondrial health and AVF-induced hand dysfunction in human patients. Mitochondrial health will be examined in-situ using permeabilized myofibers prepared from RD patients before and after AVF surgery: mitochondrial phenotypic changes will be evaluated and their association with changes in serial hemodynamic, neurophysiological and biomechanical outcomes modulating the spect... ## Key facts - **NIH application ID:** 10694865 - **Project number:** 5R01HL148597-05 - **Recipient organization:** UNIVERSITY OF FLORIDA - **Principal Investigator:** Salvatore T. Scali - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2023 - **Award amount:** $515,943 - **Award type:** 5 - **Project period:** 2019-08-05 → 2025-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10694865 ## Citation > US National Institutes of Health, RePORTER application 10694865, Impaired Mitochondrial Energetics is a Driver of Hemodialysis Access Related Hand Dysfunction (5R01HL148597-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10694865. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*