Cunningham John, Danese Mark, Olson Kurt, Klassen Preston, Chertow Glenn M
University College London, The Middlesex Hospital, London, UK.
Kidney Int. 2005 Oct;68(4):1793-800. doi: 10.1111/j.1523-1755.2005.00596.x.
Secondary hyperparathyroidism (HPT) and abnormal mineral metabolism are thought to play an important role in bone and cardiovascular disease in patients with chronic kidney disease. Cinacalcet, a calcimimetic that modulates the calcium-sensing receptor, reduces parathyroid hormone (PTH) secretion and lowers serum calcium and phosphorus concentrations in patients with end-stage renal disease (ESRD) and secondary HPT.
We undertook a combined analysis of safety data (parathyroidectomy, fracture, hospitalizations, and mortality) from 4 similarly designed randomized, double-blind, placebo-controlled clinical trials enrolling 1184 subjects (697 cinacalcet, 487 control) with ESRD and uncontrolled secondary HPT (intact PTH > or =300 pg/mL). Cinacalcet or placebo was administered to subjects receiving standard care for hyperphosphatemia and secondary HPT (phosphate binders and vitamin D). Relative risks (RR) and 95% CI were calculated using proportional hazards regression with follow-up times from 6 to 12 months. Health-related quality-of-life (HRQOL) data were obtained from the Medical Outcomes Study Short Form-36 (SF-36), and the Cognitive Functioning scale from the Kidney Disease Quality of Life instrument (KDQOL-CF).
Randomization to cinacalcet resulted in significant reductions in the risk of parathyroidectomy (RR 0.07, 95% CI 0.01-0.55), fracture (RR 0.46, 95% CI 0.22-0.95), and cardiovascular hospitalization (RR 0.61, 95% CI 0.43-0.86) compared with placebo. Changes in HRQOL favored cinacalcet, with significant changes observed for the SF-36 Physical Component Summary score and the specific domains of Bodily Pain and General Health Perception.
Combining results from 4 clinical trials, randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization, along with improvements in self-reported physical function and diminished pain. These data suggest that, in addition to its effects on PTH and mineral metabolism, cinacalcet had favorable effects on important clinical outcomes.
继发性甲状旁腺功能亢进（HPT）和矿物质代谢异常被认为在慢性肾脏病患者的骨骼和心血管疾病中起重要作用。西那卡塞是一种调节钙敏感受体的拟钙剂，可降低终末期肾病（ESRD）和继发性HPT患者的甲状旁腺激素（PTH）分泌，并降低血清钙和磷浓度。
我们对4项设计相似的随机、双盲、安慰剂对照临床试验的安全性数据（甲状旁腺切除术、骨折、住院和死亡率）进行了综合分析，这些试验纳入了1184例ESRD和未控制的继发性HPT（完整PTH≥300 pg/mL）患者（697例西那卡塞组，487例对照组）。对接受高磷血症和继发性HPT标准治疗（磷酸盐结合剂和维生素D）的患者给予西那卡塞或安慰剂。使用比例风险回归计算相对风险（RR）和95%置信区间（CI），随访时间为6至12个月。健康相关生活质量（HRQOL）数据来自医学结局研究简表36（SF-36），认知功能量表来自肾脏病生活质量量表（KDQOL-CF）。
与安慰剂相比，随机分配至西那卡塞组可显著降低甲状旁腺切除术风险（RR 0.07，95%CI 0.01-0.55）、骨折风险（RR 0.46，95%CI 0.22-0.95）和心血管住院风险（RR 0.61，95%CI 0.43-0.86）。HRQOL的变化有利于西那卡塞组，SF-36身体成分总结评分以及身体疼痛和总体健康感知的特定领域有显著变化。
综合4项临床试验的结果，随机分配至西那卡塞组可显著降低甲状旁腺切除术、骨折和心血管住院风险，同时自我报告的身体功能得到改善，疼痛减轻。这些数据表明，除了对PTH和矿物质代谢的影响外，西那卡塞对重要临床结局有有益影响。
