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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

  • Nephrology - Original Paper
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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.

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Author notes

  1. Ping Fu and Hongying Peng have contributed equally to this work.

Authors and Affiliations

  1. Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China

    Jun Xu, Yan Yang, Liang Ma & Ping Fu

  2. Department of Nephrotic Rheumatism, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, 550014, China

    Jun Xu & Hongying Peng

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Supplementary material 1 (DOCX 15 kb)

Supplementary Fig. 1: The study quality assessment for the included 8 RCTs (JPEG 317 kb)

11255_2019_2271_MOESM3_ESM.jpg

Supplementary Fig. 2: Funnel plot of patients treated with calcimimetic plus vitamin D versus vitamin D for ≥ 30% reduction in PTH and PTH achieve 150–300 pg/ml (JPEG 81 kb)

11255_2019_2271_MOESM4_ESM.jpg

Supplementary Fig. 3: Funnel plot of patients treated with calcimimetic plus vitamin D versus vitamin D for all adverse events, all-cause mortality, hypocalcemia, nausea/vomiting, diarrhea, muscle spasms and headache (JPEG 102 kb)

Supplementary material 5 (DOCX 24 kb)

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Xu, J., Yang, Y., Ma, L. et al. 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. Int Urol Nephrol 51, 2027–2036 (2019). https://doi.org/10.1007/s11255-019-02271-6

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