Annals of Internal Medicine
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
Background: Vitamin D compounds are widely used to prevent and treat secondary hyperparathyroidism. Purpose: To determinewhether 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 wereidentified. 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 (relativerisk, 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 meandifference, 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 insome 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.
Ann Intern Med. 2007;147:840-853. For author affiliations, see end of text. www.annals.org
llstages of chronic kidney disease (CKD) are associated with signiﬁcantly increased rates of all-cause and cardiovascular mortality (1). Several risk factors for death have been identiﬁed and targeted by interventions, but registry data have not shown substantial improvements in survival of people with end-stage kidney disease over the past 2 decades (2). Abnormalities of bone metabolism andmineralization, which are risk factors for death in CKD, occur early and become universal as kidney function declines (3). A frequent pattern of biochemical abnormalities includes increased serum phosphorus and parathyroid hormone (PTH) levels, whereas levels of serum calcium may be low, normal, or elevated. These changes are associated with alterations in bone mineral homeostasis, increased bone fragility(4, 5), vascular and soft tissue calciﬁcation (6, 7), muscle dysfunction (8), adverse cardiovascular outcomes, and increased mortality (9). Compared with PTH levels of 16.5 to 33.0 pmol/L (150 to 300 pg/mL), levels greater than 66 pmol/L (600 pg/mL) are reported to be associated
See also: Print Editors’ Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841 Editorial comment. . . . .. . . . . . . . . . . . . . . . . . . . . 880 Web-Only Appendix Tables Appendix Figures Conversion of graphics into slides
840 © 2007 American College of Physicians
with a 10% increased risk for death (10). Similar mortality data have been observed for increased serum phosphorus and calcium levels (10). Interventions that are widely used to improve biochemical markers of bone and mineral...