Chertow Glenn M, Blumenthal Samuel, Turner Stewart, Roppolo Michael, Stern Leonard, Chi Eric M, Reed John
Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, California, USA.
Clin J Am Soc Nephrol. 2006 Mar;1(2):305-12. doi: 10.2215/CJN.00870805. Epub 2006 Jan 25.
Active vitamin D derivatives attenuate the severity of secondary hyperparathyroidism but often increase serum calcium (Ca) and phosphorus (P) as a result of enhanced intestinal absorption. The calcimimetic cinacalcet HCl lowers parathyroid hormone (PTH) and tends to decrease Ca x P. A 16-wk, open-label clinical trial was conducted in adult hemodialysis patients who had controlled PTH (biointact PTH [biPTH] 80 to 160 pg/ml) and elevated Ca x P (> 55 mg2/dl2) and were receiving paricalcitol > 6 microg/wk (or an equipotent dose of an alternative active vitamin D derivative). At the start of the study, active vitamin D derivatives were decreased to a mean equivalent dose of paricalcitol 6 microg/wk, and cinacalcet was titrated from 30 mg/d to a maximum possible dose of 180 mg/d. Of the 72 study patients, 53 (74%) completed 8 wk of dose titration with cinacalcet. In response to cinacalcet, the following mean percentage changes were observed: biPTH, -1.8%; Ca, -9.7% (P < 0.0001), phosphorus, -11.1% (P < 0.0001), and Ca x P, -20.1% (P < 0.0001). At the end of the study, approximate Kidney Disease Outcomes Quality Initiative targets for biPTH (< or = 160 pg/ml) were achieved in 85% (45 of 53) of patients and for Ca x P (< or = 55 mg2/dl2) in 72% (38 of 53) of patients. Concurrent achievement of both targets occurred in 47% (25 of 53) of patients. In this open-label clinical trial, hemodialysis patients who had controlled PTH but elevated Ca x P and were taking moderate- to high-dose active vitamin D derivatives achieved improved control of mineral metabolism with a combination of low-dose active vitamin D derivatives and cinacalcet. The long-term effects of this treatment regimen on clinical outcomes should be tested prospectively.
活性维生素D衍生物可减轻继发性甲状旁腺功能亢进的严重程度，但由于肠道吸收增强，常导致血清钙（Ca）和磷（P）升高。拟钙剂西那卡塞盐酸盐可降低甲状旁腺激素（PTH），并倾向于降低Ca×P。对接受帕立骨化醇>6μg/周（或等效剂量的其他活性维生素D衍生物）、PTH得到控制（生物活性完整PTH[biPTH]80至160pg/ml）且Ca×P升高（>55mg²/dl²）的成年血液透析患者进行了一项为期16周的开放标签临床试验。在研究开始时，将活性维生素D衍生物降至帕立骨化醇平均等效剂量6μg/周，并将西那卡塞从30mg/d滴定至最大可能剂量180mg/d。72例研究患者中，53例（74%）完成了8周的西那卡塞剂量滴定。对西那卡塞的反应观察到以下平均百分比变化：biPTH，-1.8%；Ca，-9.7%（P<0.0001），磷，-11.1%（P<0.0001），以及Ca×P，-20.1%（P<0.0001）。在研究结束时，85%（53例中的45例）的患者达到了生物活性完整PTH（≤160pg/ml）的近似肾脏病预后质量倡议目标，72%（53例中的38例）的患者达到了Ca×P（≤55mg²/dl²）的目标。47%（53例中的25例）的患者同时实现了两个目标。在这项开放标签临床试验中，PTH得到控制但Ca×P升高且正在服用中高剂量活性维生素D衍生物的血液透析患者，通过低剂量活性维生素D衍生物和西那卡塞联合使用，实现了矿物质代谢的更好控制。该治疗方案对临床结局的长期影响应进行前瞻性测试。
