Division of Renal Diseases, Washington University School of Medicine, St Louis, MO, USA.
Nephrol Dial Transplant. 2013 Sep;28(9):2260-8. doi: 10.1093/ndt/gft227. Epub 2013 Jun 19.
Chronic kidney disease (CKD) is associated with elevations in serum phosphate, calcium-phosphorus product and bone-specific alkaline phosphatase (BAP), with attendant risks of cardiovascular and bone disorders. Active vitamin D can suppress parathyroid hormone (PTH), but may raise serum calcium and phosphate concentrations. Paricalcitol, a selective vitamin D activator, suppressed PTH in CKD patients (stages 3 and 4) with secondary hyperparathyroidism (SHPT) with minimal changes in calcium and phosphate metabolism.
The VITAL study enrolled patients with CKD stages 2-4. We examined the effect and relationship of paricalcitol to calcium and phosphate metabolism and bone markers in a post hoc analysis of VITAL. The study comprised patients with diabetic nephropathy enrolled in a double-blind, placebo-controlled, randomized trial of paricalcitol (1 or 2 μg/day). Urinary and serum calcium and phosphate, serum BAP, and intact PTH (iPTH) concentrations were measured throughout the study.
Baseline demographics and calcium, phosphate, PTH (49% with iPTH <70 pg/mL), and BAP concentrations were similar between groups. A transient, modest yet significant increase in phosphate was observed for paricalcitol 2 μg/day (+0.29 mg/dL; P < 0.001). Dose-dependent increases in serum and urinary calcium were observed; however, there were few cases of hypercalcemia: one in the 1-μg/day group (1.1%) and three in the 2-μg/day group (3.2%). Significant reductions in BAP were observed that persisted for 60 days after paricalcitol discontinuation (P < 0.001 for combined paricalcitol groups versus placebo). Paricalcitol dose-dependent reductions in iPTH were observed. Paricalcitol in CKD patients (±SHPT) was associated with modest increases in calcium and phosphate.
Paricalcitol reduces BAP levels, which may be beneficial for reducing vascular calcification.
Trial is registered with ClinicalTrials.gov, number NCT00421733.
慢性肾脏病（CKD）与血清磷酸盐、钙磷乘积和骨特异性碱性磷酸酶（BAP）升高有关，伴有心血管和骨骼疾病的风险。活性维生素 D 可以抑制甲状旁腺激素（PTH），但可能会升高血清钙和磷酸盐浓度。帕立骨化醇，一种选择性维生素 D 激活剂，可抑制伴有继发性甲状旁腺功能亢进症（SHPT）的 CKD 患者（3 期和 4 期）的 PTH，对钙和磷酸盐代谢的影响最小。
VITAL 研究纳入了 CKD 2-4 期的患者。我们在 VITAL 的一项事后分析中，研究了帕立骨化醇对钙和磷酸盐代谢及骨标志物的影响及其相关性。该研究包括糖尿病肾病患者，他们参加了帕立骨化醇（1 或 2μg/天）的双盲、安慰剂对照、随机试验。在整个研究过程中测量了尿和血清钙、磷、血清 BAP 和完整 PTH（iPTH）浓度。
基线人口统计学特征和钙、磷、PTH（49%的患者 iPTH<70pg/mL）和 BAP 浓度在各组之间相似。帕立骨化醇 2μg/天组观察到磷酸盐短暂、适度但显著升高（+0.29mg/dL；P<0.001）。观察到血清和尿钙剂量依赖性增加；然而，仅有少数高钙血症病例：1μg/天组 1 例（1.1%），2μg/天组 3 例（3.2%）。帕立骨化醇停药后 60 天观察到 BAP 显著降低（联合帕立骨化醇组与安慰剂相比，P<0.001）。观察到帕立骨化醇剂量依赖性的 iPTH 降低。在伴有（或不伴有）SHPT 的 CKD 患者中，帕立骨化醇与钙和磷酸盐的适度增加相关。
帕立骨化醇降低 BAP 水平，这可能有利于减少血管钙化。
该试验在 ClinicalTrials.gov 注册，编号为 NCT00421733。
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