Chonchol Michel, Locatelli Francesco, Abboud Hanna E, Charytan Chaim, de Francisco Angel L M, Jolly Shivinder, Kaplan Mark, Roger Simon D, Sarkar Shyamal, Albizem Moetaz B, Mix T Christian H, Kubo Yumi, Block Geoffrey A
University of Colorado Health Science Center, Division of Renal Diseases and Hypertension, Denver, CO 80262, USA.
Am J Kidney Dis. 2009 Feb;53(2):197-207. doi: 10.1053/j.ajkd.2008.09.021. Epub 2008 Dec 24.
Secondary hyperparathyroidism is observed in patients with early chronic kidney disease (CKD). This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis.
Double-blind, randomized, 32-week, phase 3 study.
SETTING & PARTICIPANTS: 404 participants with stage 3 or 4 CKD from 73 centers in 9 countries.
Cinacalcet:placebo (3:1 ratio).
OUTCOMES & MEASUREMENTS: Proportion of participants with a mean decrease of 30% or greater in intact parathyroid hormone (iPTH) level, proportion with iPTH level of 70 or less or 110 or less pg/mL (stage 3 and 4 CKD, respectively), and mean percentage of iPTH change from baseline, all during the efficacy-assessment phase.
A greater proportion of cinacalcet than placebo participants achieved a 30% or greater decrease in iPTH level (74% versus 28%; P < 0.001), corresponding to a 43.1% decrease in iPTH level from baseline (cinacalcet) compared with a 1.1% increase (placebo). At week 32, serum calcium levels were 8.9 +/- 0.8 mg/dL (-8.9%; cinacalcet) and 9.9 +/- 0.6 mg/dL (+0.8%; placebo), phosphorus levels were 4.5 +/- 1.0 mg/dL (+21.4%) and 4.0 +/- 0.7 mg/dL (+6.8%), and calcium-phosphorus product values were 40.1 +/- 8.3 mg(2)/dL(2) (+18.9%) and 38.9 +/- 6.9 mg(2)/dL(2) (+17.1%), respectively. During the study course, 62% (cinacalcet) and 1% (placebo) of participants experienced 2 consecutive serum calcium concentrations less than 8.4 mg/dL. They generally were asymptomatic and without significant clinical consequences. Treatment generally was well tolerated, and most adverse events were mild to moderate in severity.
The study was not designed to assess the effects of cinacalcet on vascular calcification, bone histomorphometric parameters, or other clinical outcomes. It is not known whether the observed differences in changes in iPTH levels are clinically more important than observed differences in changes in serum calcium or phosphorus levels or dosages of vitamin D sterols and phosphate binders.
These data show that cinacalcet treatment in patients with CKD not receiving dialysis can decrease plasma iPTH levels, but with frequent (albeit generally asymptomatic) serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus levels.
在早期慢性肾脏病（CKD）患者中可观察到继发性甲状旁腺功能亢进。本研究调查了西那卡塞对未接受透析的CKD患者继发性甲状旁腺功能亢进的安全性和有效性。
双盲、随机、为期32周的3期研究。
来自9个国家73个中心的404例3或4期CKD患者。
西那卡塞：安慰剂（3:1比例）。
在疗效评估阶段，血清全段甲状旁腺激素（iPTH）水平平均降低30%或更多的参与者比例、iPTH水平≤70或≤110 pg/mL（分别对应3期和4期CKD）的参与者比例，以及iPTH较基线变化的平均百分比。
与安慰剂组相比，更多接受西那卡塞治疗的参与者iPTH水平降低了30%或更多（74%对28%；P<0.001），西那卡塞组iPTH水平较基线降低了43.1%，而安慰剂组升高了1.1%。在第32周时，血清钙水平分别为8.9±0.8 mg/dL（降低8.9%；西那卡塞组）和9.9±0.6 mg/dL（升高0.8%；安慰剂组），磷水平分别为4.5±1.0 mg/dL（升高21.4%）和4.0±0.7 mg/dL（升高6.8%），钙磷乘积值分别为40.1±8.3 mg²/dL²（升高18.9%）和38.9±6.9 mg²/dL²（升高17.1%）。在研究过程中，62%（西那卡塞组）和1%（安慰剂组）的参与者连续两次血清钙浓度低于8.4 mg/dL。他们通常无症状，也无显著临床后果。治疗总体耐受性良好，大多数不良事件为轻至中度。
本研究未设计评估西那卡塞对血管钙化、骨组织形态计量学参数或其他临床结局的影响。尚不清楚观察到的iPTH水平变化差异在临床上是否比血清钙或磷水平变化差异或维生素D固醇及磷结合剂剂量差异更重要。
这些数据表明，未接受透析的CKD患者使用西那卡塞治疗可降低血浆iPTH水平，但会频繁出现（尽管通常无症状）血清钙水平低于8.4 mg/dL以及血清磷水平升高的情况。
