口服帕立骨化醇用于治疗血液透析或腹膜透析患者的继发性甲状旁腺功能亢进。

Oral paricalcitol for the treatment of secondary hyperparathyroidism in patients on hemodialysis or peritoneal dialysis.

作者信息

Ross Edward A, Tian Jin, Abboud Hanna, Hippensteel Richard, Melnick Joel Z, Pradhan Rajendra S, Williams Laura A, Hamm L Lee, Sprague Stuart M

机构信息

Division of Nephrology, Hypertension, and Transplantation, University of Florida, Gainesville, FL 32610-0224, USA.

出版信息

Am J Nephrol. 2008;28(1):97-106. doi: 10.1159/000109398. Epub 2007 Oct 3.

DOI:10.1159/000109398

PMID:17914251

Abstract

BACKGROUND/AIMS: Secondary hyperparathyroidism is a common complication of chronic kidney disease, resulting from inactivation of vitamin D receptor signaling and phosphate retention. Selective activation of vitamin D receptors with intravenous paricalcitol significantly reduced parathyroid hormone (PTH) levels with no significant hypercalcemia or hyperphosphatemia in predialysis and hemodialysis (HD) patients. This study investigates the effects of oral paricalcitol to reduce PTH in patients receiving chronic HD and peritoneal dialysis (PD).

METHODS

Eighty-eight patients were randomized in double-blind fashion to receive paricalcitol or placebo for 12 weeks. The dose of the study drug was adjusted weekly using the previous week's intact PTH (iPTH) level as well as calcium and Ca x P product levels. The primary end points were efficacy (two consecutive iPTH decreases of >or=30%) and safety (two consecutive calcium measurements >11.0 mg/dl). Markers of biochemical bone activity were followed.

RESULTS

Demographic characteristics were similar between treatment groups. The mean paricalcitol doses (three times a week) over the entire treatment period for subjects with baseline iPTH <or=500 pg/ml and iPTH >500 pg/ml were 3.9 and 7.6 microg, respectively. A statistically significant decrease in iPTH was seen after week 1, with a mean 30% reduction occurring by week 3. A significantly greater proportion of both HD and PD paricalcitol subjects [83% (33/40) and 100% (18/18), respectively] achieved two consecutive >or=30% decreases in iPTH. The treatment groups were not statistically different in regard to the hypercalcemia safety end point. Phosphate binder use and mean serum phosphorus levels were not different between the treatment groups. The markers of bone activity improved in the treated subjects and worsened in those on placebo.

CONCLUSION

Paricalcitol provides a rapid and sustained reduction of PTH in both HD and PD patients with minimal effect on serum calcium and phosphorus and no significant difference in adverse events as compared with placebo.

摘要

背景/目的：继发性甲状旁腺功能亢进是慢性肾脏病的常见并发症，由维生素D受体信号失活和磷潴留所致。静脉注射帕立骨化醇选择性激活维生素D受体可显著降低透析前和血液透析（HD）患者的甲状旁腺激素（PTH）水平，且无明显高钙血症或高磷血症。本研究探讨口服帕立骨化醇对接受慢性HD和腹膜透析（PD）患者降低PTH的效果。

方法

88例患者以双盲方式随机分组，接受帕立骨化醇或安慰剂治疗12周。根据前一周的完整PTH（iPTH）水平以及钙和钙磷乘积水平每周调整研究药物剂量。主要终点为疗效（连续两次iPTH降低≥30%）和安全性（连续两次血钙测量>11.0mg/dl）。跟踪生化骨活性标志物。

结果

治疗组间人口统计学特征相似。基线iPTH≤500pg/ml和iPTH>500pg/ml的受试者在整个治疗期间每周三次的平均帕立骨化醇剂量分别为3.9μg和7.6μg。第1周后iPTH出现统计学显著下降，到第3周平均下降30%。HD和PD帕立骨化醇治疗组中分别有显著更高比例的患者[分别为83%（33/40）和100%（18/18）]实现iPTH连续两次降低≥30%。治疗组在高钙血症安全性终点方面无统计学差异。治疗组间磷结合剂使用情况和平均血清磷水平无差异。治疗患者的骨活性标志物改善，而安慰剂组患者的骨活性标志物恶化。