a Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital , Chulalongkorn University , Bangkok , Thailand.
b Department of Pharmacy Practice , Chulalongkorn University , Bangkok , Thailand.
Ren Fail. 2019 Nov;41(1):326-333. doi: 10.1080/0886022X.2018.1562356.
Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT.
In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation.
In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet.
The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery.
ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.
继发性甲状旁腺功能亢进症（SHPT）与心血管疾病、骨折和死亡率的高发率有关。本研究旨在证明西那卡塞治疗对伴有严重 SHPT 的慢性血液透析患者慢性肾脏病-矿物质和骨异常（CKD-MBD）标志物的有效性。
在第 1 阶段，30 名成年 HD 患者被随机分配到西那卡塞或对照组，进行 12 周的治疗，以探索甲状旁腺激素（iPTH）降低>30%的目标。在第 2 阶段，45 名患者参与了进一步的研究，以探索西那卡塞对 CKD-MBD 参数的影响，随访 24 周，西那卡塞停药后再随访 12 周。
在第 1 阶段，两组患者的基线血清 iPTH 水平无差异[对照组为 1374（955，1639）pg/ml，西那卡塞组为 1191（1005，1884）pg/ml]，治疗组达到 iPTH 目标的患者比例显著更高[80%比 13%，p=0.001]。在第 2 阶段，24 周随访时观察到 iPTH、成纤维细胞生长因子 23（FGF-23）、抗酒石酸酸性磷酸酶 5b（TRACP5b）显著降低，甲状旁腺体积缩小，血管钙化稳定，停药后明显反弹。
即使在伴有严重 SHPT 的慢性血液透析患者中，西那卡塞的疗效仍明显。此外，还观察到骨标志物和 FGF-23 的改善以及血管钙化的稳定。因此，西那卡塞可对严重 SHPT 中的 CKD-MBD 产生有益作用，可能是甲状旁腺切除术之前的有效降 PTH 治疗方法，也是不适合手术的患者的替代治疗方法。
ClinicalTrials.gov：NCT02056730。注册日期：2014 年 2 月 4 日。
