{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:53:14Z","timestamp":1782280394140,"version":"3.54.5"},"posted":{"date-parts":[[2025,1,22]]},"group-title":"Pathology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Chronic kidney disease \u2013 mineral bone disorder (CKD-MBD) is a syndrome that begins early in CKD, contributes to CKD-associated mortality, and includes components of FGF23 elevation, \u03b1klotho deficiency, CKD-stimulated vascular disease, and renal osteodystrophy. Hyperphosphatemia, occurring in later stages of CKD, is also driven by mechanisms of CKD-MBD, and has been shown to stimulate vascular calcification. In a mouse model of Alport CKD that is resistant to vascular calcification, we examine the effects of a high-phosphate Western-type diet on the CKD-MBD, and test whether the diet promotes induction of vascular calcification.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An X-linked Col4a5 deficient murine homolog of Alport Syndrome (CKD) and wild type (WT) littermates were fed an animal protein 1.2% high phosphate diet or a standard vegetable protein diet. At disease progression equivalent to CKD stage 4-5, we examined kidney histology for fibrosis, blood for BUN (marker of CKD), and markers of CKD-MBD disease progression, kidney tissue for klotho production, and aorta histology and tissue mRNA and protein analysis for vascular calcification.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The Western high Pi diet produced hyperphosphatemia in the CKD animals compared to WT and increased plasma PTH (1880 from 110 pg \/ ml), FGF23 c-term (670 from 120 pg \/ ml), and FGF23 intact (3780 from 280 pg \/ ml), and reduced kidney klotho mRNA and protein (57-67% reduction) (all p &lt; 0.01). Referenced against the CKD animals fed vegetable-based diet, the Western high phosphate-fed CKD animals showed higher levels of plasma PTH and FGF23s. In the wild-type control mice with normal renal function, Western diet produced increased PTH, intact FGF23, and reduced renal klotho (all p &lt;0.01). Vascular smooth muscle transdifferentiation and vascular calcification was not induced by Western high phosphate diet in this model of CKD.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our results show that a Western-style high-phosphate diet advances elements of the CKD-MBD. Renal klotho, FGF23 and PTH are affected by diet even with normal kidney function, suggesting a need for early intervention in the management of phosphate homeostasis as a component of CKD therapy. Additionally, CKD, klotho, and FGF23 all are associated with early aging. Therefore, our findings suggest that a Western high Pi diet accelerates aging and would contribute to the systemic complications of CKD \u2013 cardiac disease, osteodystrophy, and vascular disease.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.17.633378","type":"posted-content","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T13:50:25Z","timestamp":1737553825000},"source":"Crossref","is-referenced-by-count":2,"title":["The Impact of a Western Diet High in Phosphate on the CKD-MBD in an Alport Syndrome Model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8704-0133","authenticated-orcid":false,"given":"Matthew J.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Nephrology, Washington University in Saint Louis, Saint Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-877X","authenticated-orcid":false,"given":"Hiral M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nephrology, Washington University in Saint Louis, Saint Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0576-542X","authenticated-orcid":false,"given":"Carley B.","family":"Halling","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nephrology, Washington University in Saint Louis, Saint Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-9099","authenticated-orcid":false,"given":"Keith A.","family":"Hruska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nephrology, Washington University in Saint Louis, Saint Louis, MO, USA"},{"name":"Department of Cell Biology, Washington University in Saint Louis, Saint Louis, MO, USA"},{"name":"Department of Medicine, Nephrology, Washington University in Saint Louis, Saint Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041022250427000_2025.01.17.633378v1.1","unstructured":"Centers for Disease Control and Prevention A, GA: US Department of Health and Human Services. 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