{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:17:20Z","timestamp":1787008640336,"version":"build-2736575974"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T00:00:00Z","timestamp":1622160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006484","name":"Vifor Pharma Ltd","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006484","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study evaluates the effects of active (1\u03b1-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of the PubMed, Embase and Cochrane Library databases (up to 14 May 2020) was performed to identify randomized, placebo-controlled trials of single-agent, oral AVD therapies in adults with ND-CKD and SHPT. Only studies with \u226530 participants per arm and \u22656\u2009weeks in duration were eligible. The outcome of interest was the number of subjects with an episode of hypercalcaemia. A meta-analysis of eligible studies was conducted using Comprehensive Meta-Analysis software (version 3.0).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six studies (five evaluating paricalcitol, one evaluating alfacalcidol) involving 799 patients were identified. Treatment durations ranged from 16\u2009weeks to 2\u2009years. The weekly doses of paricalcitol administered were 7 (three studies) and 14\u2009\u00b5g (two studies); the weekly dose of alfacalcidol was 1.75\u20137.0\u2009\u00b5g. Across all studies, rates of hypercalcaemia were 1.1\u201343.3% with AVD versus 0\u20133.4% with placebo. Meta-analysis of the six studies showed that AVD was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (odds ratio: 6.63, 95% confidence interval: 2.37, 18.55; P\u2009&amp;lt;\u20090.001). Two separate sensitivity analyses (one excluded a study identified as having a high risk of bias; the second excluded two studies that accounted for a large proportion of observed hypercalcaemia events) indicated the primary meta-analysis findings were robust.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with placebo, AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfab091","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T17:29:05Z","timestamp":1620408545000},"page":"2437-2443","source":"Crossref","is-referenced-by-count":26,"title":["Active vitamin D increases the risk of hypercalcaemia in non-dialysis chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-6252","authenticated-orcid":false,"given":"Mario","family":"Cozzolino","sequence":"first","affiliation":[{"name":"Renal Division and Laboratory of ExperimentalNephrology, Department of Health Sciences, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Bernard","sequence":"additional","affiliation":[{"name":"Department of Biometrics, Vifor Pharma Ltd, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A","family":"Csomor","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Vifor Pharma Ltd, Glattbrugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"2021110804505872000_sfab091-B1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.2215\/CJN.06040710","article-title":"Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options","volume":"6","author":"Cunningham","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"2021110804505872000_sfab091-B2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/sj.ki.5002009","article-title":"Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease","volume":"71","author":"Levin","year":"2007","journal-title":"Kidney Int"},{"key":"2021110804505872000_sfab091-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.kisu.2017.04.001","article-title":"Kidney Disease: Improving Global Outcomes CKD-MBD Work Group. 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