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拟钙剂在继发性甲状旁腺功能亢进透析患者中的临床及实际应用

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism.

作者信息

Bover Jordi, Ureña Pablo, Ruiz-García César, daSilva Iara, Lescano Patricia, del Carpio Jacqueline, Ballarín José, Cozzolino Mario

机构信息

Department of Nephrology, Puigvert Foundation, Barcelona, Spain; Sant Pau Biomedical Research Institute, REDinREN Renal Research Network, Barcelona, Spain;

Department of Nephrology and Dialysis, Landy General Health Clinic, Paris, France; Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France; and.

出版信息

Clin J Am Soc Nephrol. 2016 Jan 7;11(1):161-74. doi: 10.2215/CJN.01760215. Epub 2015 Jul 29.

Abstract

CKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD-related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions.

摘要

慢性肾脏病(CKD)及与CKD相关的矿物质和骨代谢紊乱(CKD-MBD)与心血管疾病高发及高死亡率风险相关。在随机临床试验(RCT)中,尚无单一药物干预措施被证明可降低透析患者的高死亡风险,但多项有力的二次分析表明,控制CKD-MBD相关因素及继发性甲状旁腺功能亢进具有重要的潜在益处。西那卡塞的出现,其在钙敏感受体上具有独特的作用模式,代表了在控制CKD-MBD方面向前迈出的重要一步。此外,新的RCT已确凿表明,西那卡塞可改善与CKD-MBD相关的所有代谢异常的目标水平达成情况,还可能减缓透析患者血管和瓣膜钙化的进展。然而,关于西那卡塞对硬性结局的影响的最终结论仍不明确。西那卡塞的耐受性受到频繁的副作用限制,如恶心、呕吐、低钙血症和甲状旁腺激素过度抑制,这可能会带来一些管理难题,尤其是对于那些缺乏该药物使用经验的人。在此背景下,本综述旨在总结关于西那卡塞的研究结果,直至并包括最近的ADVANCE和EVOLVE RCT的发表,以及近期的事后分析,并根据现有信息和个人经验,就如何改善与西那卡塞相关的最常见不良事件的临床管理提供实用指导。此外,还将关注西那卡塞治疗较少见的副作用及建议采取的预防措施。

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