Cinacalcet Increases Calcium Excretion in Hypercalcemic Hyperparathyroidism After Kidney Transplantation
Cinacalcet Increases Calcium Excretion in Hypercalcemic Hyperparathyroidism After Kidney Transplantation
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DOI：
10.1097/tp.0b013e318186b7fb
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发表时间：
2008-10-15
期刊：
影响因子：
6.2
通讯作者：
Sunder-Plassmann, Gere
中科院分区：
文献类型：
--
作者：
Borchhardt, Kyra A.;Heinzl, Harald;Sunder-Plassmann, Gere
背景西那卡塞降低肾移植患者高钙血症甲状旁腺功能亢进的血清钙。作用机制尚未完全了解。我们假设西那卡塞增加了肾脏对钙的清除，从而改善了肾移植患者的高钙血症。我们前瞻性研究了西那卡塞（30 mg/d）在治疗前6周对32例持续性高钙性甲状旁腺功能亢进（Ca > 2.6 mmol/L [10.4 mg/dL]，全段甲状旁腺激素> 60 pg/mL）患者血清和24小时尿钙浓度的影响，并计算了钙排泄分数。次要终点为血清磷酸盐和肾小管最大磷酸盐（经肾小球滤过率校正）、全段甲状旁腺激素和血清肌酐。所有患者的血清钙浓度均下降（从2.77降至2.51 mmol/L; P < 0.0001），钙排泄分数在治疗前2周迅速增加，从1.06增加至1.78%（P < 0.0001），此后下降至1.37%（P < 0.05，与早期治疗相比）。同时，血清磷酸盐和肾小球滤过率校正的肾小管最大磷酸盐分别从0.79 mmol/l显著增加到0.85 mmol/l和0.88 mmol/l（P < 0.05），从0.52 mmol/l显著增加到0.61 mmol/l（P < 0.005）和0.62 mmol/l（P < 0.0001 vs.基线）。全段甲状旁腺激素无明显下降。血清肌酐保持稳定。我们提供的证据表明，西那卡塞对肾移植后持续性甲状旁腺功能亢进患者的降钙作用至少部分是由尿钙排泄增加引起的。
Background. Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. The mechanism of action is not fully understood. We hypothesized that cinacalcet increases renal elimination of calcium, thereby improving hypercalcemia in kidney transplant recipients.Methods. We prospectively examined the effect of cinacalcet (30 mg/d) during the first 6 weeks of treatment on serum and 24 hrs urinary calcium concentration and calculated fractional calcium excretion in 32 patients with sustained hypercalcemic hyperparathyroidism (Ca > 2.6 mmol/L [10.4 mg/dL], intact parathyroid hormone > 60 pg/mL). Secondary endpoints were serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate, intact parathyroid hormone and serum creatinine.Results. Serum calcium concentrations decreased in all patients (from 2.77 to 2.51 mmol/L; P < 0.0001), fractional calcium excretion increased rapidly in the first 2 weeks of treatment from 1.06 to 1.78% (P < 0.0001), and decreased thereafter to 1.37% (P < 0.05 vs. early treatment). Simultaneously serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate increased significantly from 0.79 to 0.85 to 0.88 mmol/l, (P < 0.05), and from 0.52 to 0.61 (P < 0.005) and 0.62 (P < 0.0001 vs. baseline), respectively. Intact parathyroid hormone did not decrease significantly. Serum creatinine remained stable.Conclusion. We provide evidence that the calcium lowering effect of cinacalcet in patients with persistent hyperparathyroidism after kidney transplantation is caused, at least in part, by increased urinary calcium excretion.