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Clin Kidney J. 2015 Feb;8(1):41-8. doi: 10.1093/ckj/sfu122. Epub 2014 Dec 2.

Effect of oral vitamin D analogs on mortality and cardiovascular outcomes among adults with chronic kidney disease: a meta-analysis.

Author information

1
Department of Medical Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada.
2
Department of Community Health Sciences, Cumming School of Medicine , University of Calgary , Calgary, AB , Canada.
3
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.
4
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.
5
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.

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.

KEYWORDS:

cardiovascular outcomes; clinical trials; meta-analysis; mortality; vitamin D

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