Supplementary Material for: Cinacalcet for Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: A Meta-Analysis of Randomized Controlled Trials

<b><i>Background:</i></b> Cinacalcet could decrease serum calcium, phosphate, and parathyroid hormone (PTH) in previous meta-analyses. However, the effect of cinacalcet on the new biomarkers such as fibroblast growth factor-23 (FGF-23), bone markers, and vascular calcification are still unestablished. We conducted a meta-analysis to examine the effects of cinacalcet on all laboratory and clinical spectrums of chronic kidney disease-mineral bone disorders (CKD-MBD). <b><i>Methods:</i></b> A systematic literature search was conducted in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov to identify randomized controlled trials (RCTs) comparing the effect of cinacalcet relative to standard treatment on CKD-MBD surrogate markers and clinical outcomes. Random-effect models were used to compute the weighted mean difference for continuous variables and the risk ratio for binary variables. <b><i>Results:</i></b> Twenty-four RCTs (10,031 dialysis patients) were identified. Besides lowering effects on calcium, phosphate, and PTH, cinacalcet significantly reduced bone resorptive marker (tartrate-resistant acid phosphatase 5b) but unaltered bone formation markers (bone alkaline phosphatase and osteocalcin). Cinacalcet also resulted in significant higher risk of hypocalcemia, nausea, vomiting, and diarrhea. Cinacalcet significantly lowered serum FGF-23 level, although unaltered all-cause mortalities. <b><i>Conclusions:</i></b> Use of cinacalcet in dialysis patients improves several CKD-MBD-related surrogate markers. However, the benefit on all-cause mortalities was not demonstrated.

**背景**：西那卡塞（cinacalcet）在既往荟萃分析（meta-analysis）中可降低血清钙、磷及甲状旁腺激素（parathyroid hormone, PTH）水平。然而，西那卡塞对成纤维细胞生长因子-23（fibroblast growth factor-23, FGF-23）、骨标志物及血管钙化等新型生物标志物的作用仍未明确。本研究遂开展一项荟萃分析，旨在探讨西那卡塞对慢性肾脏病-矿物质和骨异常（chronic kidney disease-mineral bone disorders, CKD-MBD）全实验室及临床谱的影响。
**方法**：系统检索MEDLINE、Scopus、Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials）及ClinicalTrials.gov，筛选比较西那卡塞相较于标准治疗对CKD-MBD替代标志物及临床结局影响的随机对照试验（randomized controlled trials, RCTs）。采用随机效应模型（random-effect models）计算连续变量的加权均数差（weighted mean difference）与二分类变量的风险比（risk ratio）。
**结果**：共纳入24项随机对照试验，涉及10031名透析患者。除可降低血钙、血磷及甲状旁腺激素水平外，西那卡塞还可显著降低骨吸收标志物——抗酒石酸酸性磷酸酶5b（tartrate-resistant acid phosphatase 5b），但对骨形成标志物（骨碱性磷酸酶（bone alkaline phosphatase）及骨钙素（osteocalcin））无显著影响。此外，西那卡塞会显著增加低钙血症（hypocalcemia）、恶心（nausea）、呕吐（vomiting）及腹泻（diarrhea）的发生风险。虽然西那卡塞可显著降低血清FGF-23水平，但未改变全因死亡率（all-cause mortalities）。
**结论**：透析患者使用西那卡塞可改善多项与CKD-MBD相关的替代标志物，但尚未证实其对全因死亡率存在获益。