Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials

Abstract

Background and objectives: Vitamin D deficiency is highly prevalent among patients with chronic kidney disease (CKD). The benefits and harms of vitamin D supplementation (ergocalciferol or cholecalciferol) were assessed in patients with nondialysis-dependent CKD, dialysis-dependent CKD, and renal transplant recipients.

Design, setting, participants, & measurements: MEDLINE (1966 to September 2009), SCOPUS (September 2009), and nephrology conference proceedings were searched for relevant observational and randomized controlled trials (RCTs). Treatment effects were summarized as mean differences (MDs) with 95% confidence intervals (CIs) using a random effects model. Separate analyses were conducted for observational studies and RCTs.

Results: Twenty-two studies (17 observational and 5 RCTs) were included. There was a significant improvement in 25-hydroxyvitamin D (MD 24.1 ng/ml, 95% CI 19.6 to 28.6) and an associated decline in parathyroid hormone (PTH) levels (MD -41.7 pg/ml, 95% CI -55.8 to -27.7) among observational studies. PTH reduction was higher in dialysis patients. Among RCTs, there was a significant improvement in 25-hydroxyvitamin D (MD 14 ng/ml, 95% CI 5.6 to 22.4) and an associated decline in PTH levels (MD -31.5 pg/ml, 95% CI -57 to -6.1). A low incidence of hypercalcemia and hyperphosphatemia was reported with vitamin D supplementation. Cardiovascular and skeletal effects of vitamin D supplementation have not been studied. Included studies were mostly of low to moderate quality.

Conclusions: Available evidence from low-to-moderate quality observational studies and fewer RCTs suggests that vitamin D supplementation improves biochemical endpoints. However, whether such improvements translate into clinically significant outcomes is yet to be determined.

Figure 1.

Study flow diagram: Included studies and reasons for exclusion of studies.

Figure 2.

Effect of vitamin D supplementation on 25(OH)D levels at the end of treatment period among observational studies in CKD.

Figure 3.

Effect of vitamin D supplementation on PTH levels at the end of treatment period among observational studies in CKD.

Figure 4.

Effect of vitamin D supplementation on PTH levels at the end of treatment period among RCTs in CKD.