{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:52:38Z","timestamp":1793908358868,"version":"4.8.0"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Vitamin D deficiency is common in chronic kidney disease (CKD). Vitamin D\/vitamin D receptor (VDR) signaling intersects inflammation, oxidative stress\/mitochondrial injury, fibrogenic pathways, the renin\u2013angiotensin\u2013aldosterone system (RAAS), and the gut\u2013kidney axis, providing a biologic rationale for renoprotection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Narrative review; literature identified from PubMed\/MEDLINE, Embase, Web of Science, and Cochrane Library (January 2000\u2013August 2025). Adult CKD populations (non-dialysis, dialysis, transplant) were included. Outcomes covered biologic\/surrogate (e.g., proteinuria, estimated glomerular filtration rate [eGFR] slope) and hard endpoints (kidney failure, major cardiovascular events, fractures, mortality).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nutritional vitamin D reliably corrects deficiency and improves laboratory profiles; VDR activators (VDRAs) suppress secondary hyperparathyroidism (SHPT). However, consistent benefits on hard outcomes have not been demonstrated across CKD settings, likely reflecting heterogeneity (baseline vitamin D status, stage, co-therapies, endpoints) and formulation\/dosing differences (D\u2083 vs. D\u2082; cholecalciferol vs. calcifediol; steady vs. bolus). Safety considerations (hypercalcemia\/mineral imbalance) apply to active agents and high-dose bolus regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A pragmatic approach is warranted: replete deficiency with nutritional vitamin D (prefer D\u2083; consider calcifediol when faster repletion or persistent SHPT is relevant), avoid mega-bolus dosing, and reserve active VDRAs for clear SHPT indications with careful calcium\u2013phosphate\u2013parathyroid hormone (PTH) monitoring\u2014rather than positioning vitamin D as disease-modifying therapy for unselected CKD. Future trials should enrich truly deficient, higher-risk phenotypes, standardize regimens, and prioritize event-driven hard endpoints with embedded mechanistic markers to confirm on-target biology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1643415","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:24:23Z","timestamp":1760419463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Vitamin D and chronic kidney disease: mechanisms, clinical implications, and future perspectives"],"prefix":"10.3389","volume":"12","author":[{"given":"Hong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santao","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 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