Block Geoffrey A, Zeig Steven, Sugihara Jared, Chertow Glenn M, Chi Eric M, Turner Stewart A, Bushinsky David A
Denver Nephrologists, Denver, CO 80230, USA.
Nephrol Dial Transplant. 2008 Jul;23(7):2311-8. doi: 10.1093/ndt/gfn026. Epub 2008 Feb 29.
Adequate control of all four KDOQI biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca x P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca x P among haemodialysis patients with secondary hyperparathyroidism (sHPT).
This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160-430 pg/mL) (approximately iPTH 300-800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30-180 mg/day) during an 8-week dose-titration phase to achieve biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L) and efficacy was assessed over 8 weeks. At week 2 of the study, subjects receiving vitamin D sterols had doses reduced to the equivalent of 2 mcg of paricalcitol three times a week or 6 mcg/week. Among the efficacy endpoints were the proportion of subjects with mean biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L), with mean Ca x P <or=55 mg(2)/dL(2) (4.4 mmol(2)/L(2)) and with both simultaneously during the assessment phase.
The majority of subjects (n = 375) reached the assessment phase of the study and were included in efficacy analyses; 39 subjects withdrew due to adverse events. Sixty-two percent of subjects achieved the biPTH target, 83% achieved the Ca x P target and 54% reached both targets. Treatment reduced biPTH by 35% (P < 0.0001), calcium by 11% (P < 0.0001), phosphorus by 7% (P < 0.0001) and Ca x P by 17% (P < 0.0001). The proportion of subjects with values for biPTH, for Ca x P and for both biPTH and Ca x P within the target range during the assessment phase did not differ between subjects who received cinacalcet together with vitamin D sterols, and those who received cinacalcet alone.
Among subjects with moderate to severe sHPT undergoing haemodialysis, combined therapy with cinacalcet and low doses of vitamin D sterols improved achievement of the biochemical targets for CKD-MBD recommended by the KDOQI guidelines.
对慢性肾脏病-矿物质和骨异常（CKD-MBD）的所有四个美国肾脏病改善全球结果（KDOQI）生化指标进行充分控制仍然困难，在接受血液透析的患者中，实现这一目标的患者不到6%。这四个指标包括甲状旁腺激素（PTH）、钙（Ca）、磷（P）和钙磷乘积（Ca×P）。本研究的目的是确定西那卡塞联合低剂量维生素D甾醇治疗是否能改善继发性甲状旁腺功能亢进（sHPT）血液透析患者的PTH和Ca×P控制情况。
这项多中心、开放标签研究纳入了患有中度至重度sHPT（平均血清生物活性甲状旁腺激素>160 - 430 pg/mL）（大约全段甲状旁腺激素300 - 800 pg/mL或ng/L）的血液透析受试者（N = 444）。在为期8周的剂量滴定阶段，西那卡塞依次滴定（30 - 180 mg/天），以实现生物活性甲状旁腺激素≤160 pg/mL（大约全段甲状旁腺激素300 pg/mL或ng/L），并在8周内评估疗效。在研究的第2周，接受维生素D甾醇治疗的受试者将剂量减至相当于帕立骨化醇2 mcg，每周三次或6 mcg/周。疗效终点包括在评估阶段，平均生物活性甲状旁腺激素≤160 pg/mL（大约全段甲状旁腺激素300 pg/mL或ng/L）的受试者比例、平均钙磷乘积≤55 mg²/dL²（4.4 mmol²/L²）的受试者比例以及两者同时达标的受试者比例。
大多数受试者（n = 375）进入了研究的评估阶段并纳入疗效分析；39名受试者因不良事件退出。62%的受试者达到了生物活性甲状旁腺激素目标，83%的受试者达到了钙磷乘积目标，54%的受试者两个目标均达成。治疗使生物活性甲状旁腺激素降低了35%（P < 0.0001），钙降低了11%（P < 0.0001），磷降低了7%（P < 0.0001），钙磷乘积降低了17%（P < 0.0001）。在评估阶段，生物活性甲状旁腺激素、钙磷乘积以及两者均在目标范围内的受试者比例，在接受西那卡塞联合维生素D甾醇治疗的受试者与单独接受西那卡塞治疗的受试者之间没有差异。
在接受血液透析的中度至重度sHPT受试者中，西那卡塞与低剂量维生素D甾醇联合治疗改善了KDOQI指南推荐的CKD-MBD生化指标的达标情况。
