摘要
目的:探究西那卡塞在伴不同严重程度继发性甲状旁腺功能亢进(SHPT)的维持性血液透析(MHD)患者中的疗效与安全性。方法:本研究为开放标签、平行分组、多中心研究,包括第一阶段为期32周的药物干预研究,以及第二阶段为期20周的试验后随访。根据基线全段甲状旁腺激素(iPTH)水平将患者为轻度(≥300 pg/mL且<600 pg/mL)、中度(≥600 pg/mL且<900 pg/mL)或重度(≥900 pg/mL)SHPT组。在第一阶段,受试者在常规治疗的基础上口服西那卡塞1次/d,剂量从25 mg逐步递增至100 mg,以达到iPTH≥150 pg/mL且<300 pg/mL的目标值。在第二阶段,患者可自行选择是否继续服用西那卡塞。主要疗效指标为第20周和第32周iPTH达标率。结果:共纳入750例SHPT患者,其中轻度组275例(36.7%),中度组224例(29.9%),重度组251例(33.4%)。治疗20周时,三组患者iPTH达标率分别为35.5%、28.3%和12.4%(P<0.001)。治疗32周时,这一比例分别上升至41.2%、27.7%和15.9%(P<0.001)。西那卡塞治疗显著降低了各组患者的血钙、血磷和成纤维细胞生长因子23(FGF-23)水平。随着SHPT程度加重,患者需要的西那卡塞治疗剂量增加,低钙血症发生率也随之升高。试验后随访20周,分别有40.0%和47.6%的患者仍维持了iPTH和FGF-23较基线下降≥30%。结论:MHD患者在SHPT早期阶段启动西那卡塞治疗有助于提高疗效,应重视对西那卡塞不良反应的观察及处理。
Objective:To Evaluate the efficacy and safety of cinacalcet in maintenance hemodialysis patients with varying severity of secondary hyperparathyroidism(SHPT).Methodology:This open-label,parallel-group,multicenter study consisted of a 32-week cohort study followed by a 20-week post-trial follow-up.Patients were stratified by baseline iPTH levels into mild(≥300 pg/mL and<600 pg/mL),moderate(≥600 pg/mL and<900 pg/mL),or severe(≥900 pg/mL)categories.During the cohort study,participants received oral cinacalcet once daily,titrated from 25 mg to 100 mg,to achieve a target iPTH of≥150 pg/mL and<300 pg/mL alongside conventional therapy.In the post-trial follow-up,patients chose whether to continue cinacalcet at their own expense.The primary efficacy outcome was the proportion of patients achieving the target iPTH level at weeks 20 and 32.Results:A total of 750 patients were enrolled,including 275 with mild,224 with moderate,and 251 with severe SHPT.The primary efficacy outcome was achieved by 35.5%,28.3%,and 12.4%of patients in the mild-to-severe groups,respectively,at week 20(P<0.001).By week 32,these rates increased to 41.2%,27.7%,and 15.9%,respectively(P<0.001).Cinacalcet significantly reduced serum calcium,phosphorus,and fibroblast growth factor 23(FGF-23)levels across all SHPT severity groups.Higher cinacalcet doses and increased hypocalcemia incidence were observed in patients with more severe SHPT.During the post-trial follow-up,40.0%and 47.6%of patients maintained≥30%reductions in iPTH and FGF-23,respectively.Conclusion:These findings support initiating cinacalcet treatment at an early stage of SHPT in patients on maintenance hemodialysis.However,attention should be paid to treatment related adverse events.
作者
安玉
付平
姜埃利
章海涛
陈佩玲
刘章锁
陈晓农
凌毅生
肖观清
叶建明
陈靖
楼季庄
王德光
何强
倪兆慧
王世相
丁国华
毛永辉
左力
张爱华
陈朝生
牛建英
刘虹
李雪梅
黄杰
刘志红
AN Yu;FU Ping;JIANG Aili;ZHANG Haitao;CHEN Peiling;LIU Zhangsuo;CHEN Xiaonong;LING Yisheng;XIAO Guanqing;YE Jianming;CHEN Jing;LOU Jizhuang;WANG Deguang;HE Qiang;NI Zhaohui;WANG Shixiang;DING Guohua;MAO Yonghui;ZUO Li;ZHANG Aihua;CHEN Chaosheng;NIU Jianying;LIU Hong;LI Xuemei;HUANG Jie;LIU Zhihong(National Clinical Research Center for Kidney Diseases,Jinling Hospital,Nanjing 210016,China;West China Hospital of Sichuan University,Kidney Research Laboratory,Division of Nephrology and National Clinical Research Center for Geriatrics,Chengdu 610041,China;The Second Hospital of Tianjin Medical University,Tianjin Institute of Urology,Department of Kidney Disease&Blood Purification Treatment,Tianjin 300211,China;The First Affiliated Hospital of Zhengzhou University,Department of Nephrology,Zhengzhou 450052,China;Ruijin Hospital,School of Medicine,Shanghai Jiao Tong University,Department of Nephrology,Shanghai 200025,China;Zhongshan Hospital,Xiamen University,Department of Nephrology,Xiamen 361004,China;The First People's Hospital of Foshan,Nephrology Department,Foshan 528000,China;The First People's Hospital of Kunshan,Department of Nephrology,Kunshan 215300,China;Huashan Hospital,Shanghai Medical College,Fudan University,National Clinical Research Center for Aging and Medicine,Division of Nephrology,Shanghai 200040,China;Nanjing First Hospital,Nanjing Medical University,Division of Hemodialysis,Nanjing 210002,China;The Second Affiliated Hospital of Anhui Medical University,Department of Nephrology,Hefei 230601,China;Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital,Nephrology Division,Chengdu 610072,China;Renji Hospital,School of Medicine,Shanghai Jiaotong University,Department of Nephrology,Shanghai 200127,China;Beijing Chao-Yang Hospital,Capital Medical University,Nephrology Faculty,Department of Blood Purification,Beijing 100020,China;Renmin Hospital of Wuhan University,Division of Nephrology,Wuhan 430060,China;Beijing Hospital,Department of Nephrology,National Center of Gerontology,Beijing 100730,China;Peking University People's Hospital,Department of Nephrology,Beijing 100044,China;Xuanwu Hospital Capital Medical University,Department of Nephrology,Beijing 100053,China;The First Affiliated Hospital of Wenzhou Medical University,Department of Nephrology,Wenzhou 325000,China;The Fifth People's Hospital of Shanghai,Fudan University,Department of Nephrology,Shanghai 200240,China;The Second Xiangya Hospital,Central South University,Department of Nephrology,Key Lab of Kidney Disease and Blood Purification in Hunan,Changsha 410011,China;Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Department of Nephrology,Beijing 100730,China;Kyowa Kirin China Pharmaceutical Co.,Ltd,Department of Medical Affairs,Shanghai 201203,China)
出处
《肾脏病与透析肾移植杂志》
2025年第6期501-510,共10页
Chinese Journal of Nephrology,Dialysis & Transplantation
基金
国家自然科学基金青年项目(82300835)
江苏省卫生健康委创新中心项目(CXZX202202)。
