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The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D<jats:sub>3<\/jats:sub> and 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> in a cross-sectional analysis of participants with a range of kidney function assessed by precise measured GFR (mGFR) (N\u2009=\u2009143) and in rats with the induction and progression of experimental kidney disease. Vitamin D metabolites were assessed with LC\u2013MS\/MS. Circulating measures of 24-hydroxylation of 25(OH)D<jats:sub>3<\/jats:sub> (24,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>:25(OH)D<jats:sub>3<\/jats:sub>) precisely decreased according to mGFR in humans and progressively in rats with developing CKD. In contrast, the 1,24,25(OH)3D3: 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> vitamin D metabolite ratio increased in humans as the mGFR decreased and in rats with the induction and progression of CKD. Human participants taking cholecalciferol had higher circulating 1,24,25(OH)<jats:sub>3<\/jats:sub>D<jats:sub>3<\/jats:sub>, despite no increase of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>. This first report of circulating 1,24,25(OH)<jats:sub>3<\/jats:sub>D<jats:sub>3<\/jats:sub> in the setting of CKD provides novel insight into the uniquely altered vitamin D metabolism in this setting. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies. The potential that 24-hydroxylated products have biological activity of is an important area of future research.<\/jats:p>","DOI":"10.1038\/s41598-022-15033-9","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T18:04:08Z","timestamp":1656439448000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease"],"prefix":"10.1038","volume":"12","author":[{"given":"Mandy E.","family":"Turner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler S.","family":"Rowsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Norman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Neville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Petkovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenville","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Holden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"15033_CR1","first-page":"1","volume":"60","author":"KDIGO","year":"2017","unstructured":"KDIGO. 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