Brandi Lisbet, Egfjord Martin, Olgaard Klaus
Nephrological Department P, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Nephron Clin Pract. 2005;99(4):c128-37. doi: 10.1159/000083979. Epub 2005 Feb 17.
BACKGROUND/AIMS: The aim was to evaluate the acute effects of intravenous 1alpha(OH)D3 and 1,25(OH)2D3 on (1) plasma parathyroid hormone (PTH) and Ca2+ levels in chronic uremic patients and (2) circulating large C-terminal PTH fragments as measured by the 'whole PTH' assay compared to two different 'intact PTH' assays.
11 patients on chronic hemodialysis with plasma intact PTH >90 pg/ml were studied. At time zero 10 microg 1,25(OH)2D3 (Calcijex, Abbott, USA), or 10 microg 1alpha(OH)D3 (Etalpha, LEO, Denmark) or 10 ml of isotonic saline was injected as a bolus. Blood samples for analyses of plasma Ca2+ and plasma PTH were drawn at 0, 6, 12, 24, 48 and 72 h. The same patient was studied 3 times in a random fashion with an interval of 3 weeks. Further, 7 of the patients were studied after an injection of 6 microg 1,25(OH)2D3 intravenously.
No significant changes in plasma Ca2+ and PTH were seen after administration of saline. Twenty-four hours after administration of 1,25(OH)2D3, plasma PTH decreased from a maximum level of PTHWHOLE 151 +/- 27 to a minimum of 58 +/- 13 pg/ml; from a maximum level of PTHTOTAL 247 +/- 40 to a minimum of 99 +/- 26 pg/ml and from a maximum level of PTHINTACT 205 +/- 29 to a minimum of 83 +/- 18 pg/ml (p < 0.001). Twenty-four hours after administration of 1alpha(OH)D3, plasma PTH levels decreased from a maximum level of PTHWHOLE 155 +/- 21 to a minimum of 116 +/- 15 pg/ml; from a maximum level of PTHTOTAL 265 +/- 33 to a minimum of 221 +/- 35 pg/ml and from a maximum level of PTHINTACT 222 +/- 26 to a minimum of 182 +/- 23 pg/ml (p < 0.05). Regardless of which of the three assays that was applied, the percentage suppression of PTH following administration of 1,25(OH)2D3 was approximately 60% and following administration of 1alpha(OH)D3 approximately 20%. Significant correlations were demonstrated between the Whole and the intact PTH assays, and as expected between the 2 intact assays ('Whole'/'Intact', r = 0.92, p < 0.0001, 'Whole'/'Total', r = 0.94, p < 0.0001, 'Intact'/'Total', r = 0.97, p < 0.0001) with no influence of the two vitamin D analogs administered. Plasma Ca2+ remained stable after administration of saline. After 24 h, no increase in plasma Ca2+ was observed after administration of 1alpha(OH)D3 or after administration of 6 microg 1,25(OH)2D3, while plasma Ca2+ after administration of 10 microg 1,25(OH)2D3 increased to 1.31 +/- 0.03 mmol/l (p < 0.008). After 72 h, 1alpha(OH)D3 increased plasma Ca2+ to 1.22 +/- 0.02 mmol/l (p < 0.05) and 10 microg 1,25(OH)2D3 to 1.27 +/- 0.03 mmol/l. Plasma phosphate was within the normal range before administration of saline (1.24 +/- 0.13 mmol/l), 1,25(OH)2D3 (1.28 +/- 0.12 mmol/l) and 1alpha(OH)D3 (1.46 +/- 0.21 mmol/l). Plasma phosphate increased significantly after 24, 48 and 72 h to a maximum of 2.06 +/- 0.27 mmol/l after administration of 1,25(OH)2D3 and a maximum of 1.94 +/- 0.31 mmol/l after administration of 1alpha(OH)D3. Plasma phosphate was significantly higher after 1,25(OH)2D3 than after 1alpha(OH)D3 at 48 (p = 0.016) and 72 h (p < 0.010).
A single intravenous dose of both 10 microg 1,25(OH)2D3 and 1alpha(OH)D3 significantly suppressed plasma PTH. The acute suppressive effect of 1,25(OH)2D3 was 3 times greater than that of 1alpha(OH)D3. The increase in plasma Ca2+ after intravenous administration of 10 microg of 1,25(OH)2D3 was, however, significantly greater than that of 10 microg of 1alpha(OH)D3 (p < 0.005). The PTH response to acute administration of 10 microg of the two vitamin D analogs was in principle the same, when measured by the three different assays and resulted in a parallel shift of the PTH response curves. Thus, circulating levels of large C-terminal PTH fragments were not influenced by differences in plasma Ca2+ or by the vitamin D analog given.
背景/目的：本研究旨在评估静脉注射1α(OH)D3和1,25(OH)2D3对慢性尿毒症患者的急性影响，具体包括：(1)血浆甲状旁腺激素（PTH）和Ca2+水平；(2)与两种不同的“完整PTH”检测方法相比，通过“全段PTH”检测法测定的循环大C末端PTH片段。
选取11例血浆完整PTH>90 pg/ml的慢性血液透析患者进行研究。在时间零点，静脉推注10 μg 1,25(OH)2D3（美国雅培公司的盖三淳）、10 μg 1α(OH)D3（丹麦LEO公司的依特卡肽）或10 ml等渗盐水。在0、6、12、24、48和72小时采集血样，用于分析血浆Ca2+和血浆PTH。同一患者以随机方式进行3次研究，间隔3周。此外，7例患者在静脉注射6 μg 1,25(OH)2D3后进行研究。
注射盐水后，血浆Ca2+和PTH无显著变化。注射1,25(OH)2D3后24小时，血浆PTH从PTHWHOLE的最高水平151±27降至最低水平58±13 pg/ml；从PTHTOTAL的最高水平247±40降至最低水平99±26 pg/ml；从PTHINTACT的最高水平205±29降至最低水平83±18 pg/ml（p<0.001）。注射1α(OH)D3后24小时，血浆PTH水平从PTHWHOLE的最高水平155±21降至最低水平116±15 pg/ml；从PTHTOTAL的最高水平265±33降至最低水平221±35 pg/ml；从PTHINTACT的最高水平222±26降至最低水平182±23 pg/ml（p<0.05）。无论采用三种检测方法中的哪一种，注射1,25(OH)2D3后PTH的抑制率约为60%，注射1α(OH)D3后约为20%。全段PTH检测与完整PTH检测之间存在显著相关性，正如预期的那样，两种完整检测方法之间也存在显著相关性（“全段”/“完整”，r = 0.92，p<0.0001；“全段”/“总段”，r = 0.94，p<0.0001；“完整”/“总段”，r = 0.97，p<0.0001），且不受所给予的两种维生素D类似物的影响。注射盐水后血浆Ca2+保持稳定。24小时后，注射1α(OH)D3或6 μg 1,25(OH)2D3后血浆Ca2+未升高，而注射10 μg 1,25(OH)2D3后血浆Ca2+升高至1.31±0.03 mmol/l（p<0.008）。72小时后，1α(OH)D3使血浆Ca2+升高至1.22±0.02 mmol/l（p<0.05），10 μg 1,25(OH)2D3使其升高至1.27±0.03 mmol/l。注射盐水前血浆磷酸盐在正常范围内（1.24±0.13 mmol/l），注射1,25(OH)2D3后为（1.28±0.12 mmol/l），注射1α(OH)D3后为（1.46±0.21 mmol/l）。注射1,25(OH)2D3后24、48和72小时血浆磷酸盐显著升高，最高达到2.06±0.27 mmol/l，注射1α(OH)D3后最高达到1.94±0.31 mmol/l。在48小时（p = 0.016）和72小时（p<0.010），注射1,25(OH)2D3后的血浆磷酸盐显著高于注射1α(OH)D3后的水平。
单次静脉注射10 μg 1,25(OH)2D3和1α(OH)D3均可显著抑制血浆PTH。1,25(OH)2D3的急性抑制作用是1α(OH)D3的3倍。然而，静脉注射10 μg 1,25(OH)2D3后血浆Ca2+的升高显著大于10 μg 1α(OH)D3（p<0.005）。通过三种不同检测方法测定，急性注射10 μg两种维生素D类似物后PTH的反应原则上相同，且导致PTH反应曲线平行移动。因此，循环中大C末端PTH片段的水平不受血浆Ca2+差异或所给予的维生素D类似物的影响。
