Frazão J M, Elangovan L, Maung H M, Chesney R W, Acchiardo S R, Bower J D, Kelley B J, Rodriguez H J, Norris K C, Robertson J A, Levine B S, Goodman W G, Gentile D, Mazess R B, Kyllo D M, Douglass L L, Bishop C W, Coburn J W
Medical and Research Services, Veterans Affairs West Los Angeles Healthcare Center, Los Angeles, CA, USA.
Am J Kidney Dis. 2000 Sep;36(3):550-61. doi: 10.1053/ajkd.2000.16193.
Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.
对于继发性甲状旁腺功能亢进的血液透析患者，高钙血症和高磷血症常常需要停用维生素D。在短期试验中，多西骨化醇（1α-羟基维生素D₂ [1αD₂]）能有效抑制全段甲状旁腺激素（iPTH），同时血清钙和磷（P）水平的升高幅度最小。这项改良的双盲对照试验通过采用新的剂量滴定法，研究了1αD₂用于138例中度至重度继发性甲状旁腺功能亢进血液透析患者的疗效和安全性；99例患者完成了研究。继发性甲状旁腺功能亢进的血液透析患者被纳入本研究，包括洗脱期（8周）、开放标签的1αD₂治疗期（16周）以及1αD₂或安慰剂的随机双盲治疗期（8周）。每次血液透析时口服1αD₂，剂量滴定以达到目标iPTH水平为每毫升150至300皮克。基线iPTH水平（897±52 [SE] 皮克/毫升）在第1周时下降了20%±3.4%（P：<0.001），在第16周时下降了55%±2.9%；iPTH水平在安慰剂治疗期间恢复到基线，但在1αD₂治疗期间仍受到抑制。80%的患者iPTH水平下降了70%，83%的患者达到了目标水平。根据入组时的iPTH水平（<600、600至1200以及>1200皮克/毫升）对患者进行分组，结果显示iPTH水平最低的组抑制迅速；水平最高的组则需要更大剂量和更长时间的治疗。在开放标签治疗期间，血清钙和P水平分别为9.2±0.84（SD）至9.7±1.05毫克/分升和5.4±1.10至5.9±1.55毫克/分升。在双盲治疗期间，1αD₂组的血清钙水平略高于安慰剂组，但P水平无差异。在双盲治疗期间，1αD₂组和安慰剂组分别有3.26%和0.46%的血清钙测量值超过11.2毫克/分升（P：<0.01）；高钙血症期间的中位数水平为11.6毫克/分升。间歇性口服1αD₂疗法能有效抑制继发性甲状旁腺功能亢进血液透析患者的iPTH，伴有可接受的轻度高钙血症和高磷血症。
