Active vitamin D increases the risk of hypercalcaemia in non-dialysis chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis

Background. This study evaluates the effects of active (1 alpha-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT). Methods. A systematic search of the PubMed, Embase and Cochrane Library databases (up to 14 May 2020) was performed to identify randomized, placebo-controlled trials of single-agent, oral AVD therapies in adults with ND-CKD and SHPT. Only studies with >= 30 participants per arm and >= 6weeks in duration were eligible. The outcome of interest was the number of subjects with an episode of hypercalcaemia. A meta-analysis of eligible studies was conducted using Comprehensive Meta-Analysis software (version 3.0). Results. Six studies (five evaluating paricalcitol, one evaluating alfacalcidol) involving 799 patients were identified. Treatment durations ranged from 16weeks to 2years. The weekly doses of paricalcitol administered were 7 (three studies) and 14 mu g (two studies); the weekly dose of alfacalcidol was 1.75-7.0 mu g. Across all studies, rates of hypercalcaemia were 1.1-43.3% with AVD versus 0-3.4% with placebo. Meta-analysis of the six studies showed that AVD was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (odds ratio: 6.63, 95% confidence interval: 2.37, 18.55; P<0.001). Two separate sensitivity analyses (one excluded a study identified as having a high risk of bias; the second excluded two studies that accounted for a large proportion of observed hypercalcaemia events) indicated the primary meta-analysis findings were robust. Conclusions. Compared with placebo, AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT.

Automated summary

This study evaluated the effects of active vitamin D therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT). Results showed that AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT compared to placebo.