title: Effect of oral vitamin D analogs on mortality and cardiovascular outcomes among adults with chronic kidney disease: a meta-analysis.
abstract: BACKGROUND
  Vitamin D deficiency is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with all-cause and cardiovascular mortality in observational studies. However, evidence from randomized controlled trials (RCTs) supporting vitamin D supplementation is lacking. We sought to assess whether vitamin D supplementation alters the relative risk (RR) of all-cause and cardiovascular mortality, as well as serious adverse cardiovascular events, in patients with CKD, compared with placebo.
  
  
  METHODS
  PubMed/MEDLINE, EMBASE, Cochrane Library, and selected nephrology journals and conference proceedings were searched in October 2013. RCTs considered for inclusion were those that assessed oral vitamin D supplementation versus placebo in adults with CKD (≤60 mL/min/1.73 m(2)), including end-stage CKD requiring dialysis. We calculated pooled RR of mortality (all-cause and cardiovascular) and that of cardiovascular events and stratified by CKD stage, vitamin D analog and diabetes prevalence.
  
  
  RESULTS
  The search identified 4246 articles, of which 13 were included. No significant treatment effect of oral vitamin D on all-cause mortality (RR: 0.84; 95% CI: 0.47, 1.52), cardiovascular mortality (RR: 0.79; 95% CI: 0.26, 2.28) or serious adverse cardiovascular events (RR: 1.20; 95% CI: 0.49, 2.99) was observed. The pooled analysis demonstrated large variation in trials with respect to dosing (0.5 ug-200 000 IU/week) and duration (3-104 weeks).
  
  
  CONCLUSIONS
  Current RCTs do not provide sufficient or precise evidence that vitamin D supplementation affects mortality or cardiovascular risk in CKD. While its effect on biochemical endpoints is well documented, the results demonstrate a lack of appropriate patient-level data within the CKD literature, which warrants larger trials with clinical primary outcomes related to vitamin D supplementation.
authors.affiliation: Department of Medical Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Mann
authors.affiliation: Department of Community Health Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Hobbs
authors.affiliation: Department of Community Health Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada ; Division of Nephrology, Cumming School of Medicine , University of Calgary, Foothills Medical Centre , Calgary, AB , Canada.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
authors.affiliation: Department of Community Health Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada ; Department of Surgery, Cumming School of Medicine, University of Calgary, Foothills Medical Centre , Calgary, AB , Canada.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Roberts
authors.affiliation: Department of Medical Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada ; Division of Nephrology, Cumming School of Medicine , University of Calgary, Foothills Medical Centre , Calgary, AB , Canada.
authors.forename: Sofia B
authors.initials: SB
authors.lastname: Ahmed
authors.affiliation: Department of Community Health Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Rabi
keywords: cardiovascular outcomes; clinical trials; meta-analysis; mortality; vitamin D