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 (1a-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 6 weeks 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 16 weeks to 2 years. The weekly doses of paricalcitol administered were 7 (three studies) and 14 mg (two studies); the weekly dose of alfacalcidol was 1.75—7.0 mg. 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.