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Grip strength changes are a common metric used to assess AVF-associated hand disability but has previously been found to poorly correlate with the hemodynamic perturbations post-AVF placement implicating other tissue-level factors as drivers of hand outcomes. In this study, we sought to test if expression of a mitochondrial targeted catalase (mCAT) in skeletal muscle could reduce AVF-related limb dysfunction in mice with chronic kidney disease (CKD). Male and female C57BL\/6J mice were fed an adenine-supplemented diet to induce CKD prior to placement of an AVF in the iliac vascular bundle. Adeno-associated virus was used to drive expression of either a green fluorescent protein (control) or mCAT using the muscle-specific human skeletal actin (HSA) gene promoter prior to AVF creation. As expected, the muscle-specific AAV-HSA-mCAT treatment did not impact blood urea nitrogen levels (<jats:italic>P<\/jats:italic>\u2009=\u20090.72), body weight (<jats:italic>P<\/jats:italic>\u2009=\u20090.84), or central hemodynamics including infrarenal aorta and inferior vena cava diameters (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.18) or velocities (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.38). Hindlimb perfusion recovery and muscle capillary densities were also unaffected by AAV-HSA-mCAT treatment. In contrast to muscle mass and myofiber size which were not different between groups, both absolute and specific muscle contractile forces measured via a nerve-mediated in-situ preparation were significantly greater in AAV-HSA-mCAT treated mice (<jats:italic>P<\/jats:italic>\u2009=\u20090.0012 and<jats:italic>P<\/jats:italic>\u2009=\u20090.0002). Morphological analysis of the post-synaptic neuromuscular junction uncovered greater acetylcholine receptor cluster areas (<jats:italic>P<\/jats:italic>\u2009=\u20090.0094) and lower fragmentation (<jats:italic>P<\/jats:italic>\u2009=\u20090.0010) in AAV-HSA-mCAT treated mice. Muscle mitochondrial oxidative phosphorylation was not different between groups, but AAV-HSA-mCAT treated mice had lower succinate-fueled mitochondrial hydrogen peroxide emission compared to AAV-HSA-GFP mice (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). In summary, muscle-specific scavenging of mitochondrial hydrogen peroxide significantly improves neuromotor function in mice with CKD following AVF creation.<\/jats:p>","DOI":"10.1038\/s41598-024-58805-1","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T10:02:06Z","timestamp":1712656926000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondrial targeted catalase improves muscle strength following arteriovenous fistula creation in mice with chronic kidney disease"],"prefix":"10.1038","volume":"14","author":[{"given":"Kyoungrae","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Fazzone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas A.","family":"Cort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric M.","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Moerschel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria R.","family":"Palzkill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gengfu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik M.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerri A.","family":"O\u2019Malley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott A.","family":"Berceli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-029X","authenticated-orcid":false,"given":"Terence E.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8128-3203","authenticated-orcid":false,"given":"Salvatore T.","family":"Scali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"issue":"2","key":"58805_CR1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1159\/000514550","volume":"52","author":"JS Thurlow","year":"2021","unstructured":"Thurlow, J. 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