{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:11:53Z","timestamp":1791987113375,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["F31DK131914"],"award-info":[{"award-number":["F31DK131914"]}]},{"name":"NIH","award":["F31DK117550"],"award-info":[{"award-number":["F31DK117550"]}]},{"name":"NIH","award":["R01DK125459"],"award-info":[{"award-number":["R01DK125459"]}]},{"name":"NIH","award":["R01HL145528"],"award-info":[{"award-number":["R01HL145528"]}]},{"name":"NIH","award":["24PRE1242192"],"award-info":[{"award-number":["24PRE1242192"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["F31DK131914"],"award-info":[{"award-number":["F31DK131914"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["F31DK117550"],"award-info":[{"award-number":["F31DK117550"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["R01DK125459"],"award-info":[{"award-number":["R01DK125459"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["R01HL145528"],"award-info":[{"award-number":["R01HL145528"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24PRE1242192"],"award-info":[{"award-number":["24PRE1242192"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3\u2212\/\u2212). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl\/kl). We found that adenine, Col4a3\u2212\/\u2212, and kl\/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.<\/jats:p>","DOI":"10.3390\/ijms25179308","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:57:06Z","timestamp":1724817426000},"page":"9308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Mice"],"prefix":"10.3390","volume":"25","author":[{"given":"Kylie","family":"Heitman","sequence":"first","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Bollenbecker","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Bradley","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7888-2432","authenticated-orcid":false,"given":"Brian","family":"Czaya","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abul","family":"Fajol","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Madison","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4540-7915","authenticated-orcid":false,"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Komarova","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-6768","authenticated-orcid":false,"given":"Stefanie","family":"Krick","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn C.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-5171","authenticated-orcid":false,"given":"Matthew S.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Center for Exercise Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Division of Neurology, Department of Pediatrics, Children\u2019s of Alabama, The University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7512-0977","authenticated-orcid":false,"given":"Christian","family":"Faul","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.7326\/M16-0273","article-title":"Trends in Prevalence of Chronic Kidney Disease in the United States","volume":"165","author":"Murphy","year":"2016","journal-title":"Ann. 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