{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:15:57Z","timestamp":1747196157426,"version":"3.40.5"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, Ministry of Science of Technology, India","award":["BT\/PR3150\/MED\/30\/640\/2011"],"award-info":[{"award-number":["BT\/PR3150\/MED\/30\/640\/2011"]}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research, India","doi-asserted-by":"crossref","award":["5\/4\/7- 3\/2019\/NCD-II"],"award-info":[{"award-number":["5\/4\/7- 3\/2019\/NCD-II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Vitamin D plays an important role in proliferation and differentiation of cells and deficiency of vitamin D disturbs angiogenic balance. Previous studies in animal models have reported an association between serum levels of vitamin D and balance between pro- and anti-angiogenic factors. There is insufficient evidence about the effect of vitamin D on mediators of angiogenesis in patients with CKD. We investigated the effect of cholecalciferol supplementation on serum levels of angiogenic markers in non-diabetic patients with CKD stage 3\u20134. In this secondary analysis on stored samples of our previously published randomized, double-blind, placebo-controlled trial, stable patients of either sex, aged 18\u201370 years, with non-diabetic CKD stage 3\u20134 and vitamin D deficiency (serum 25-hydroxyvitamin D \u226420 ng\/ml) were randomized to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in brachial artery flow-mediated dilatation at 16 weeks. Changes in levels of serum angiogenesis markers (angiopoietin-1, angiopoietin-2, VEGF-A, VEGEF-R, and Tie-2) between groups over 16 weeks were compared. A total 120 patients were enrolled. Supplementation with cholecalciferol led to significant improvement in FMD. Serum 25(OH)D levels were similar in both groups at baseline (13.21\u00b14.78 ng\/ml and 13.40\u00b14.42 ng\/ml; p = 0.888). At 16 weeks, the serum 25(OH)D levels increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change:23.40 ng\/ml; 95% CI, 19.76 to 27.06; p&lt;0.001). Serum levels of angiogenic markers were similar at baseline. At 16 weeks, angiopoietin-2 level decreased in cholecalciferol group (mean difference:-0.73 ng\/ml, 95%CI, -1.25 to -0.20, p = 0.002) but not in placebo group (mean difference -0.46 ng\/ml, 95%CI, -1.09 to 0.17, p = 0.154), however there was no between-group difference at 16 weeks (between-group difference in mean change: -0.27 ng\/ml, 95%CI, -1.09 to 0.55, p = 0.624). Serum angiopoietin-1 level increased [mean change: 5.63 (0.51 to 10.75), p = 0.018] and VEGF-R level decreased [mean change: -87.16 (-131.89 to -42.44), p&lt;0.001] in placebo group but did not show any change in cholecalciferol group. Our data shows the changes in Ang-1, Ang-2 and Ang-1\/Ang-2 ratio after high dose oral cholecalciferol supplementation in patients with non-diabetic G3-4 CKD. The data suggests changes in circulating levels of angiogenic markers which needs to be confirmed through an adequately powered study.<\/jats:p>","DOI":"10.1371\/journal.pone.0268946","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T17:26:44Z","timestamp":1654277204000},"page":"e0268946","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cholecalciferol supplementation and angiogenic markers in chronic kidney disease"],"prefix":"10.1371","volume":"17","author":[{"given":"Jaskiran","family":"Kaur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kajal","family":"Kamboj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-928X","authenticated-orcid":true,"given":"Ashok Kumar","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prabhjot","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivekanand","family":"Jha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"issue":"1","key":"pone.0268946.ref001","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1055\/s-0038-1657610","article-title":"Angiogenesis: a dynamic balance of stimulators and inhibitors","volume":"78","author":"ML Iruela-Arispe","year":"1997","journal-title":"Thromb Haemost"},{"issue":"4","key":"pone.0268946.ref002","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/74651","article-title":"Mechanisms of angiogenesis and arteriogenesis","volume":"6","author":"P. 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