Meta-analysis: vitamin D compounds in chronic kidney disease

Ann Intern Med. 2007 Dec 18;147(12):840-53. doi: 10.7326/0003-4819-147-12-200712180-00004.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Administration Schedule
  • Humans
  • Hypercalcemia / chemically induced
  • Hyperparathyroidism, Secondary / prevention & control*
  • Hyperphosphatemia / chemically induced
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications*
  • Parathyroid Hormone / blood
  • Randomized Controlled Trials as Topic
  • Vitamin D / adverse effects
  • Vitamin D / therapeutic use*
  • Vitamins / adverse effects
  • Vitamins / therapeutic use*


  • Parathyroid Hormone
  • Vitamins
  • Vitamin D