Vervloet M G, du Buf-Vereijken P W G, Potter van Loon B-J, Manamley N, Reichert L J M, Smak Gregoor P J H
Department of Nephrology, VU University Medical Centre, Amsterdam, the Netherlands.
Neth J Med. 2013 Sep;71(7):348-54.
Secondary hyperparathyroidism is an almost inevitable complication of advanced kidney failure. The introduction of the calcimimetic cinacalcet for the treatment of secondary hyperparathyroidism in patients on dialysis was based on its ability to reduce elevated levels of parathyroid hormone (PTH). Subsequent clinical studies confirmed the beneficial effects of cinacalcet on biochemical parameters reflecting mineral disturbances and bone disease. In this review we summarise the impact of cinacalcet on biochemical, intermediate and clinical outcomes. We also present previously unpublished mineral metabolism data from 144 Dutch dialysis patients treated with cinacalcet who participated in the pan-European ECHO observational study. Although secondary hyperparathyroidism tended to be more severe in our Dutch cohort, compared with the entire ECHO cohort, cinacalcet was nevertheless effective in reducing PTH in these patients. Two recent clinical studies evaluated, respectively, the efficacy of cinacalcet in improving the intermediate endpoint of cardiovascular calcifications (ADVANCE trial), and its impact on clinical outcomes, including all-cause mortality and cardiovascular events (EVOLVE trial). The ADVANCE trial provided evidence that cinacalcet may indeed improve calcification in both large arteries and cardiac valves. The EVOLVE trial, however, did not meet its clinical primary endpoint (time to all-cause mortality, myocardial infarction, hospitalisation for unstable angina, heart failure or a peripheral vascular event), although secondary and sensitivity analysis suggested a beneficial effect. The clinical implications of these important studies are also addressed in this review.
继发性甲状旁腺功能亢进是晚期肾衰竭几乎不可避免的并发症。拟钙剂西那卡塞用于治疗透析患者继发性甲状旁腺功能亢进，是基于其降低甲状旁腺激素（PTH）升高水平的能力。随后的临床研究证实了西那卡塞对反映矿物质紊乱和骨病的生化指标的有益作用。在本综述中，我们总结了西那卡塞对生化、中间和临床结局的影响。我们还展示了来自144名接受西那卡塞治疗的荷兰透析患者的此前未发表的矿物质代谢数据，这些患者参与了泛欧洲ECHO观察性研究。尽管与整个ECHO队列相比，继发性甲状旁腺功能亢进在我们的荷兰队列中往往更严重，但西那卡塞在降低这些患者的PTH方面仍然有效。最近的两项临床研究分别评估了西那卡塞改善心血管钙化中间终点的疗效（ADVANCE试验），以及其对临床结局的影响，包括全因死亡率和心血管事件（EVOLVE试验）。ADVANCE试验提供了证据表明西那卡塞确实可能改善大动脉和心脏瓣膜的钙化。然而，EVOLVE试验未达到其临床主要终点（至全因死亡率、心肌梗死、不稳定型心绞痛住院、心力衰竭或外周血管事件发生的时间），尽管次要分析和敏感性分析提示有有益作用。本综述还探讨了这些重要研究的临床意义。
