{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:28Z","timestamp":1786480288974,"version":"build-2736575974"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Baseline eGFR does not affect the effects of supplementation with vitamin D\n                            <jats:sub>3<\/jats:sub>\n                            on the incidence of cardiovascular events or invasive cancer.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Vitamin D\n                            <jats:sub>3<\/jats:sub>\n                            supplementation results in a greater reduction in serum parathyroid hormone concentration in those with lower versus higher eGFR.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We assessed for heterogeneity by baseline eGFR of the effects of vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      and\/or 1 g\n                      <jats:italic toggle=\"yes\">\u03a9<\/jats:italic>\n                      -3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline eGFR was available for 15,917 participants. Participants\u2019 mean age was 68 years, and 51% were women. Vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng\/ml; 95% CI, 12 to 13.1 ng\/ml), without heterogeneity by eGFR (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      and placebo was larger with lower eGFR (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction=0.05): \u20136.9 (95% CI, \u201310.5 to \u20133.4), \u20135.8 (95% CI, \u20138.3 to \u20133.4), \u20134 (95% CI, \u20135.9 to \u20132.2), and \u20133.8 (95% CI, \u20135.6 to \u20132) pg\/ml for eGFR &lt;60, 60\u201374, 75\u201389, and \u226590 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      , respectively. Effects of vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      supplementation on cardiovascular events (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction=0.61) and cancer (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0006472022","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T11:05:24Z","timestamp":1667214324000},"page":"2095-2105","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Effects of Vitamin D3 Supplementation on Cardiovascular and Cancer Outcomes by eGFR in VITAL"],"prefix":"10.34067","volume":"3","clinical-trial-number":[{"clinical-trial-number":"nct01169259","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-7428","authenticated-orcid":false,"given":"Christine P.","family":"Limonte","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington"},{"name":"Kidney Research Institute, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8461-5111","authenticated-orcid":false,"given":"Leila R.","family":"Zelnick","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington"},{"name":"Kidney Research Institute, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6449-0243","authenticated-orcid":false,"given":"Andrew N.","family":"Hoofnagle","sequence":"additional","affiliation":[{"name":"Kidney Research Institute, University of Washington, Seattle, Washington"},{"name":"Department of Laboratory Medicine, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Thadhani","sequence":"additional","affiliation":[{"name":"Office of the Chief Academic Officer, Mass General Brigham, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal L.","family":"Melamed","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-0980","authenticated-orcid":false,"given":"Samia","family":"Mora","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-0842","authenticated-orcid":false,"given":"Nancy R.","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1265-9190","authenticated-orcid":false,"given":"Heike","family":"Luttmann-Gibson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard D.","family":"Sesso","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-6907","authenticated-orcid":false,"given":"I-Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Buring","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-7595","authenticated-orcid":false,"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1571-7592","authenticated-orcid":false,"given":"Ian H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington"},{"name":"Kidney Research Institute, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"B1-20250825","first-page":"97","article-title":"The prevalence of hypovitaminosis D among US adults: Data from the NHANES III","volume":"15","author":"Zadshir","year":"2005","journal-title":"Ethn Dis"},{"key":"B2-20250825","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/CIRCULATIONAHA.107.706127","article-title":"Vitamin D deficiency and risk of cardiovascular 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