{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:13:48Z","timestamp":1784754828649,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Vitamin D deficiency, widely prevalent in patients with chronic kidney disease (CKD) could play a role in the pathogenesis of cardiovascular disease (CVD) by causing alterations in endothelial and immune function. We investigated the change in immune and vascular functions following vitamin D supplementation in non-diabetic subjects with stage 3-4 CKD and vitamin D deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this single-arm study, non-diabetic CKD subjects aged 18\u201375 years, eGFR 15-60 ml\/min\/1.73m<jats:sup>2<\/jats:sup>, and serum 25-hydroxyvitamin D<jats:sub>3<\/jats:sub> levels &amp;lt;20 ng\/ml were enrolled. Enrolled subjects received a directly observed oral dose of 300,000 IU cholecalciferol at baseline and 8 weeks. Outcome assessments, including immunological, vascular, endothelial, inflammatory, and biochemical parameters, were measured at baseline and 16 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 62 subjects were studied. The mean age was 44 \u00b1 12 years with 58% men. TH1 cells decreased from 17% (9%, 27%) to 11% (6%, 16%) (p=0.002) and TH2 cells increased from 9% (5%, 16%) to 16% (10%, 27%) (p=0.001) after cholecalciferol treatment. A significant increase in mRNA expression of vitamin D-responsive genes (cathelicidin, IL-10, VDR, and CYP27B1) was observed. The levels of pro-inflammatory cytokines (IFN-\u03b3, TNF-\u03b1, IL-23, and IL-6) decreased whereas anti-inflammatory cytokines (IL-4, IL-10, and IL-13) showed an increase. Cholecalciferol treatment improved flow-mediated dilatation (FMD): 8.2% (6.2%, 12.1%) at baseline to 14.1% (10.0%, 20.1%) at 16 weeks (p&amp;lt;0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study confirms that cholecalciferol supplementation influenced immune function as it favored the TH2\/TH1 phenotype, favorably affected the levels of inflammatory markers and mRNA expression of vitamin D responsive genes, and improved vascular function in CKD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/www.ctri.nic.in<\/jats:uri>, identifier CTRI\/2019\/10\/021494.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1555304","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:31:19Z","timestamp":1745472679000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of cholecalciferol on immune and vascular function in non-diabetic chronic kidney disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Kajal","family":"Kamboj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna","family":"Pariki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manphool","family":"Singhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Lal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Naik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok Kumar","family":"Yadav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivekanand","family":"Jha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/heartasia-2016-010809","article-title":"Cardiovascular disease in patients with chronic kidney disease: a neglected subgroup","volume":"8","author":"Subbiah","year":"2016","journal-title":"Heart Asia"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.12581018","article-title":"Vitamin D and cardiovascular complications of CKD: what's next","volume":"14","author":"Banerjee","year":"2019","journal-title":"Clin J Am Soc Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1017459","article-title":"The association between vitamin D deficiency and risk of renal event: Results from the Korean cohort study for outcomes in patients with chronic kidney disease (KNOW-CKD)","volume":"10","author":"Lee","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2011.03.020","article-title":"Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies","volume":"58","author":"Pilz","year":"2011","journal-title":"Am J Kidney Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/ncpendmet0716","article-title":"Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity","volume":"4","author":"Adams","year":"2008","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/nu7105392","article-title":"Mechanisms underlying the regulation of innate and adaptive immunity by vitamin D","volume":"7","author":"Wei","year":"2015","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1196\/annals.1402.036","article-title":"Vitamin D in defense of the human immune response","volume":"1117","author":"Adams","year":"2007","journal-title":"Ann N Y Acad Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1017\/S0029665111001650","article-title":"and immune function: an overview","volume":"71","author":"Hewison M. 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