OBJECTIVES : To evaluate the effect of active vitamin D therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT).

METHODS : A systematic literature search of the PubMed database from inception until 19 June 2018 was performed for randomized controlled trials (RCTs) of single-agent, oral active (1α-hydroxylated) vitamin D therapies versus placebo in adult patients with ND-CKD and SHPT. Only studies with ≥30 participants per arm and ≥6 weeks in duration were eligible for inclusion. The primary outcome of interest was the number of subjects with hypercalcaemia deemed as related, or potentially related, to the study drug by the study investigator. A meta-analysis was performed using Comprehensive Meta-Analysis software version 3.0 (Biostat, Inc.). The combined odds ratio (OR) and the corresponding 95% confidence intervals (95% CIs) were calculated for the eligible studies.

RESULTS : A total of 6 placebo-controlled RCTs (5 studies evaluated paricalcitol, 1 evaluated alfacalcidol) involving 799 patients were eligible for inclusion. Study duration ranged from 16 weeks to 2 years. Weekly doses of paricalcitol administered were 7 µg (3 studies) and 14 µg (2 studies), while the weekly dose in the alfacalcidol study was 1.75−7.0 µg. Across the studies, rates of hypercalcaemia ranged from 1.1−43.3% versus 0−3.4% in the active vitamin D and placebo groups, respectively. Overall, active vitamin D therapy was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (OR: 6.63, 95% CIs: 2.37, 18.55, P<0.001).

CONCLUSIONS : Compared with placebo, treatment with active vitamin D therapy significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT. These findings highlight the need for new therapies for the treatment of SHPT in this patient population that avoid undesired elevations in serum calcium. Limitations of the current analysis included the small number of studies included and heterogeneity in the study designs.