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REVIEW

Meta-analysis: Vitamin D Compounds in Chronic Kidney Disease

Suetonia C. Palmer, MBChB; David O. McGregor, PhD; Petra Macaskill, PhD; Jonathan C. Craig, PhD; Grahame J. Elder, PhD; and Giovanni F.M. Strippoli, MD, MPH(Hons), MM

18 December 2007 | Volume 147 Issue 12 | Pages 840-853

Background: Vitamin D compounds are widely used to prevent and treat secondary hyperparathyroidism.

Purpose: To determine whether vitamin D therapy improves biochemical markers of mineral metabolism and cardiovascular and mortality outcomes in chronic kidney disease.

Data Sources: MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to July 2007), and Cochrane databases were searched without language restriction.

Study Selection: Randomized, controlled trials of vitamin D compounds in chronic kidney disease were identified.

Data Extraction: Two authors independently extracted data.

Data Synthesis: Seventy-six trials were identified for inclusion; 3667 participants were enrolled. Vitamin D compounds did not reduce the risk for death, bone pain, vascular calcification, or parathyroidectomy. Compared with placebo, established vitamin D sterols were associated with an increased risk for hypercalcemia (relative risk, 2.37 [95% CI, 1.16 to 4.85]) and hyperphosphatemia (relative risk, 1.77 [CI, 1.15 to 2.74]) but did not show a consistent reduction in parathyroid hormone (PTH) levels. Compared with placebo, more recently developed vitamin D analogues were associated with hypercalcemia (relative risk, 5.15 [CI, 1.06 to 24.97]) but not hyperphosphatemia, and levels of PTH were reduced (weighted mean difference, –10.77 pmol/L [CI, –20.51 to –1.03 pmol/L]). For suppression of PTH, intravenous administration was superior to oral vitamin D, but higher intravenous doses were used.

Limitations: Few studies reported patient-level outcomes, including mortality (8 of 76 trials), and only 5 trials directly compared the effects of treatment with newer vitamin D compounds versus established ones. Heterogeneity in some comparisons remained unexplained by metaregression analyses.

Conclusion: Vitamin D compounds do not consistently reduce PTH levels, and beneficial effects on patient-level outcomes are unproven. The value of vitamin D treatment for people with chronic kidney disease remains uncertain.

Editors' Notes Context Clinicians often treat patients with kidney disease with vitamin D compounds to prevent secondary hyperparathyroidism. Contribution This meta-analysis of 76 randomized trials found no good evidence that vitamin D compounds reduced risk for death, bone pain, vascular calcification, or need for parathyroidectomy in patients with chronic kidney disease. Compared with placebo, established vitamin D sterols increased risk for hypercalcemia and hyperphosphatemia, whereas newer vitamin D analogues increased hypercalcemia but not hyperphosphatemia. Direct comparisons found no clear benefits of newer analogues over established agents. Implication Though commonly used, vitamin D compounds for chronic kidney disease have unclear benefits and potential harms. —The Editors

 

Author and Article Information

From the Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand; School of Public Health, University of Sydney, and Centre for Transplant and Renal Research, Westmead Millennium Institute, Sydney, Australia; and National Health and Medical Research Council Centre for Clinical Research Excellence in Renal Medicine and The Children's Hospital at Westmead, Westmead, Australia.

Acknowledgment: The authors thank Narelle Willis (Review Group Coordinator of the Cochrane Renal Group), Ruth Mitchell (Trials Search Coordinator of the Cochrane Renal Group), and the Cochrane Renal Group for assistance with preparation of this study.

Financial Support: Partial funding for this project was provided by the Cochrane Renal Group.

Potential Financial Conflicts of Interest: Employment: G.F.M. Strippoli (Diaverum). Consultancies: G.J. Elder (Abbott). Honoraria: G.J Elder (Abbott).

Requests for Single Reprints: Suetonia C. Palmer, MBChB, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch 8001, New Zealand; or e-mail Dr. Strippoli at strippoli{at}negrisud.it.

Current Author Addresses: Dr. Palmer: Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, 8001, New Zealand.

Dr. McGregor: Department of Nephrology, Christchurch Hospital, Canterbury District Health Board, PO Box 4710, Christchurch, 8001, New Zealand.

Dr. Macaskill: The School of Public Health, Edward Ford Building, The University of Sydney, NSW 2006, Australia.

Dr. Craig: Cochrane Renal Group, Centre for Kidney Research Excellence in Renal Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia.

Dr. Elder: Department of Renal Medicine, Westmead Hospital, Westmead, NSW 2145, Australia.

Dr. Strippoli: Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro (Ch), Italy.

Author Contributions: Conception and design: S.C. Palmer, J.C. Craig, G.F.M. Strippoli.

Analysis and interpretation of the data: S.C. Palmer, G.J. Elder, J.C. Craig, P. Macaskill, G.F.M. Strippoli.

Drafting of the article: S.C. Palmer, G.F.M. Strippoli.

Critical revision of the article for important intellectual content: G.J. Elder, J.C. Craig, D.O. McGregor, G.F.M. Strippoli.

Final approval of the article: S.C. Palmer, G.J. Elder, J.C. Craig, D.O. McGregor, P. Macaskill, G.F.M. Strippoli.

Statistical expertise: P. Macaskill.

Administrative, technical, or logistic support: G.F.M. Strippoli.

Collection and assembly of data: S.C. Palmer, G.F.M. Strippoli.

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