Cinacalcet plus vitamin D versus vitamin D alone for the treatment of secondary hyperparathyroidism in patients undergoing dialysis: a meta-analysis of randomized controlled trials

Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease, particularly in end-stage renal disease. Currently, both cinacalcet and vitamin D are used to treat SHPT via two different mechanisms, but it is still unclear whether the combination use of these two drugs can be a safe and effective alternative to vitamin D alone. Therefore, the aim of this meta-analysis was to assess the efficacy and safety of cinacalcet plus vitamin D in the treatment of SHPT.

Four electronic databases, including PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, were searched for eligible publications. All randomized-controlled trials comparing cinacalcet plus vitamin D with vitamin D alone in SHPT patients undergoing dialysis were included. Mean difference (MD) with 95% confidence intervals (CIs) and risk ratios (RRs) with 95% CIs were calculated using a random-effects model or fixed-effects model. Sensitivity analysis was conducted by removing any one study successively to estimate the stability of the pooled results, and subgroup analysis was carried out to explore potential sources of heterogeneity, and funnel plots were used to test publication bias.

A total of 8 randomized-controlled trials involving 1480 patients were included in the study. Compared with vitamin D treatment, the combination use of cinacalcet and vitamin D significantly lowered serum calcium (MD − 0.82, 95% CI − 1.02 to − 0.61, P < 0.001), phosphorus (MD − 0.57, 95% CI − 0.97 to − 0.18, P = 0.005), and calcium × phosphorus product (MD − 9.41, 95% CI − 10.00 to − 8.82, P < 0.001). However, there was no difference in serum parathyroid hormone (PTH, MD 43.99, 95% CI − 49.22 to 137.20, P = 0.35), ≥ 30% reduction in PTH (RR 1.02, 95% CI 0.69–1.52, P = 0.91), and PTH achieve 150–300 pg/ml (RR 0.88, 95% CI 0.68–1.15, P = 0.35). Moreover, the combination therapy did not increase the risk of all adverse events, all-cause mortality, diarrhea, muscle spasms, and headache (all P > 0.05), but had a higher risk of hypocalcemia (RR 17.98, 95% CI 5.68–56.99, P < 0.001), and nausea or vomiting (RR 3.47, 95% CI 2.25–5.35, P < 0.001).

In comparison with vitamin D alone, the combination use of cinacalcet and vitamin D significantly lowered serum calcium, phosphorus, and the calcium × phosphorus product, and did not increase the risk of all adverse events, all-cause mortality, diarrhea, muscle spasms, and headache, whereas had no effect on serum PTH and increased the risk of hypocalcemia and nausea or vomiting. Future studies are needed to assess the effects of cinacalcet plus vitamin D on PTH level, cardiovascular events, and other clinical outcomes in larger samples with longer durations.