{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:23:56Z","timestamp":1784165036194,"version":"3.55.0"},"reference-count":29,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"abstract":"<jats:p>&lt;p&gt;Introduction: Serum concentrations of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) decline as chronic kidney disease (CKD) advances, becoming insufficient without effective vitamin D repletion and driving onset of secondary hyperparathyroidism (SHPT). Randomized controlled trials (RCTs) in non-dialysis CKD patients have established that extended-release calcifediol (ERC) effectively raises 25D and 1,25D and reduces elevated intact parathyroid hormone (iPTH) despite the progressive loss of renal cytochrome P450 25D-1\u03b1-hydroxylase (CYP27B1), suggesting its potential usefulness in treating SHPT in end-stage kidney disease (ESKD). Methods: This pilot RCT explored the safety and efficacy of oral ERC to raise serum total 25D to \u226550 ng\/mL, normalize circulating 1,25D, and reduce elevated iPTH in ESKD patients requiring regular hemodialysis (HD). Forty-four adults from 13 US clinics requiring HD three times per week were washed out from iPTH-lowering therapies and randomized 3:1 to 26 weeks of treatment with ERC (300 \u00b5g\/HD) or placebo. Participants had a mean age of 56.4 \u00b1 11.6 years, body mass index of 32.7 \u00b1 8.1 kg\/m2, 46% were female, 68% black, 30% white, and 24% Hispanic. At randomization, iPTH had to be 300 to &lt;1,200 pg\/mL, 25D &lt;50 ng\/mL, corrected serum calcium &lt;9.8 mg\/dL, and phosphorus &lt;6.5 mg\/dL. These parameters were monitored weekly or biweekly and 1,25D quarterly. Results: Mean (\u00b1SE) serum total 25D rose with ERC treatment from 24.1 \u00b1 1.7 ng\/mL at baseline (BL) to steady-state levels of 157.7 \u00b1 10.4 (p &lt; 0.001) after 12 weeks, with all individual levels exceeding 50 ng\/mL but varying inversely with body weight. Serum 25D levels declined with placebo treatment from 36.0 \u00b1 5.3 to 30.6 \u00b1 5.5 ng\/mL. Mean 1,25D rose from 9.4 \u00b1 1.2 to 50.7 \u00b1 7.8 pg\/mL (p &lt; 0.001) with ERC and concentrations surpassed 19.9 pg\/mL (lower limit of normal) in 93% of participants. Mean iPTH increased 19.8 \u00b1 10.6% from BL with placebo (497.6 \u00b1 69.2 to 593.1 \u00b1 95.1 pg\/mL) but decreased 1.7 \u00b1 4.7% (p &lt; 0.05) with ERC (530.4 \u00b1 29.4 to 529.6 \u00b1 43.7 pg\/mL). A strong correlation was observed with ERC treatment between serum 1,25D and 25D (R2 = 0.8248; p &lt; 0.001) indicating that, on average, 1,25D normalized as 25D reached \u226550 ng\/mL. Increases in mean serum calcium or phosphorus, episodes of hypercalcemia, or treatment-emergent adverse events were not observed with ERC treatment. Conclusion: ERC safely raised serum total 25D, normalized low serum 1,25D, and stabilized elevated plasma iPTH in this pilot placebo-controlled RCT involving ESKD patients requiring regular HD. The observed increases in 1,25D indicated that ERC restored adequate endogenous vitamin D hormone production via substrate-driven conversion to calcitriol in extrarenal tissues expressing CYP27B1, thereby preventing further SHPT progression. &lt;\/p&gt;<\/jats:p>","DOI":"10.1159\/000546615","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T12:02:50Z","timestamp":1749038570000},"page":"109-119","source":"Crossref","is-referenced-by-count":12,"title":["Extended-Release Calcifediol Normalized 1,25-Dihydroxyvitamin D and Prevented Progression of Secondary Hyperparathyroidism in Hemodialysis Patients in a Pilot Randomized Clinical Trial"],"prefix":"10.1159","volume":"57","author":[{"given":"Charles W.","family":"Bishop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0501-8571","authenticated-orcid":false,"given":"Akhtar","family":"Ashfaq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Choe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Strugnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3071-0700","authenticated-orcid":false,"given":"Keith C.","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-0179","authenticated-orcid":false,"given":"Stuart M.","family":"Sprague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002009"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2017.04.001"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1159\/000369939"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1159\/000450766"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1988.190"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2024.03.025"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfaa195"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2704"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0385"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfae293"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02140309"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw080"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfab035"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-91338-6.00023-9"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-59-6-1063"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/nu14183690"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae290"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1159\/000499187"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1159\/000499160"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.2.317"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-139X.2005.18402.x"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/88.2.582S"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05490614"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1159\/000529523"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2007.12.001"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.138.suppl_5.857"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1080\/17446651.2017.1347501"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-42-2-284"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-021-01104-z"}],"container-title":["American 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