de Francisco Angel L M, Izquierdo Maria, Cunningham John, Piñera Celestino, Palomar Rosa, Fresnedo Gema Fernandez, Amado Jose A, Unzueta Mayte Garcia, Arias Manuel
Servicio de Nefrología, Hospital Universitario Valdecilla, Avda Valdecilla, s/n, Santander, 39008, Spain.
Nephrol Dial Transplant. 2008 Sep;23(9):2895-901. doi: 10.1093/ndt/gfn191. Epub 2008 Apr 19.
The parathyroid-calcium (Ca(2+)-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca(2+) concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca(2+). Increasing the sensitivity of the parathyroid gland to extracellular Ca(2+) by manipulation of the Ca(2+)-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca(2+), accounting for the simultaneous reduction of Ca(2+) and PTH seen in most patients.
The Ca(2+)-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9-22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca(2+) concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca(2+) concentration to induce hypercalcaemia and maximally inhibit PTH secretion.
Significant decreases in ionized Ca(2+) and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca(2+) and to a leftward shift of the Ca(2+)-PTH curve. Significant differences were present in all segments of the Ca(2+)-PTH curves.
The pathological rightward shift of the Ca(2+)-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.
甲状旁腺 - 钙（Ca(2 +)-PTH）曲线表示甲状旁腺激素（PTH）分泌随细胞外Ca(2 +)浓度变化的调节情况。与对照组相比，甲状旁腺功能亢进症（HPT）患者的曲线向右移位，提示甲状旁腺细胞对Ca(2 +)的敏感性降低。通过操纵钙敏感受体（CaR）来提高甲状旁腺对细胞外Ca(2 +)的敏感性可能具有治疗潜力。拟钙剂可别构修饰CaR并使其对细胞外Ca(2 +)更敏感，这解释了大多数患者中Ca(2 +)和PTH同时降低的现象。
在10例血液透析患者中评估Ca(2 +)-PTH曲线，在两次血液透析过程中，基线时完整PTH水平>300 pg/ml，一次在西那卡塞治疗前，另一次在治疗后（间隔9 - 22周）。在每个疗程中，使用2小时的低透析液Ca(2 +)浓度诱导低钙血症并最大程度刺激PTH分泌，随后立即使用2小时的高透析液Ca(2 +)浓度诱导高钙血症并最大程度抑制PTH分泌。
西那卡塞治疗后观察到离子化Ca(2 +)和完整PTH显著降低。西那卡塞治疗还导致Ca(2 +)的设定点降低以及Ca(2 +)-PTH曲线向左移位。Ca(2 +)-PTH曲线的所有段均存在显著差异。
西那卡塞治疗可能会逆转许多HPT患者中出现的Ca(2 +)-PTH曲线的病理性右移。
Zotero 插件