Fishbane Steven, Shapiro Warren B, Corry Dalila B, Vicks Steven L, Roppolo Michael, Rappaport Kenneth, Ling Xiang, Goodman William G, Turner Stewart, Charytan Chaim
Winthrop University Hospital, Department Of Nephrology, Mineola, New York 11501, USA.
Clin J Am Soc Nephrol. 2008 Nov;3(6):1718-25. doi: 10.2215/CJN.01040308.
Patients with chronic kidney disease (CKD) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) was established to guide treatment practices for these disorders. The ACHIEVE study was designed to test two treatment strategies for achieving KDOQI goals.
DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study. Subjects were randomly assigned to treatment with either cinacalcet and low-dose vitamin D (Cinacalcet-D) or flexible vitamin D alone (Flex-D) to achieve KDOQI-recommended bone mineral targets. ACHIEVE included a 6-week screening phase, including vitamin D washout, a 16-week dose-titration phase, and an 11-week assessment phase.
Of 173 subjects enrolled, 83% of Cinacalcet-D and 67% of Flex-D subjects completed the study. A greater proportion of Cinacalcet-D versus Flex-D subjects had a >30% reduction in parathyroid hormone (PTH) (68% versus 36%, P < 0.001) as well as PTH <300 pg/ml (44% versus 23%, P = 0.006). The proportion of subjects simultaneously achieving targets for intact PTH (150-300 pg/ml) and calcium-phosphorus product (Ca x P) (<55 mg2/dl2) was also greater (21% versus 14%), but this was not statistically significant. This was attributable to 19% of Cinacalcet-D subjects with a PTH value below the KDOQI target range.
Achievement of KDOQI targets was difficult, especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm.
接受透析的慢性肾脏病（CKD）患者常发生继发性甲状旁腺功能亢进，伴有钙磷代谢紊乱。美国国家肾脏基金会-肾脏病预后质量倡议（KDOQI）旨在指导这些疾病的治疗实践。ACHIEVE研究旨在测试两种实现KDOQI目标的治疗策略。
设计、地点、参与者、测量方法：接受维生素D甾醇治疗的血液透析患者参与了这项为期33周的研究。受试者被随机分配接受西那卡塞联合低剂量维生素D（西那卡塞-D组）或单纯灵活使用维生素D（灵活-D组）治疗，以实现KDOQI推荐的骨矿物质目标。ACHIEVE研究包括一个为期6周的筛查阶段（包括维生素D洗脱期）、一个为期16周的剂量滴定阶段和一个为期11周的评估阶段。
在173名入组受试者中，西那卡塞-D组83%的受试者和灵活-D组67%的受试者完成了研究。与灵活-D组相比，西那卡塞-D组有更大比例的受试者甲状旁腺激素（PTH）降低>30%（68%对36%，P<0.001）以及PTH<300 pg/ml（44%对23%，P = 0.006）。同时实现完整PTH（150 - 300 pg/ml）和钙磷乘积（Ca×P）（<55 mg²/dl²）目标值的受试者比例也更高（21%对14%），但这无统计学意义。这是由于西那卡塞-D组有19%的受试者PTH值低于KDOQI目标范围。
实现KDOQI目标困难重重，尤其是灵活-D组。维持钙磷目标值使得无法使用将PTH降低至狭窄目标范围内所需的维生素D剂量，并凸显了KDOQI治疗算法固有的局限性。
