Comparison between 1α(OH)D3 and 1,25(OH)2D3 on the Suppression of Plasma PTH Levels in Uremic Patients, Evaluated by the ‘Whole’ and ‘Intact’ PTH Assays

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Abstract
Background/Aims: The aim was to evaluate the acute effects of intravenous 1α(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. Methods: 11 patients on chronic hemodialysis with plasma intact PTH >90 pg/ml were studied. At time zero 10 µg 1,25(OH)2D3 (Calcijex, Abbott, USA), or 10 µg 1α(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 µg 1,25(OH)2D3 intravenously. Results: 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 1α(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 1α(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 1α(OH)D3 or after administration of 6 µg 1,25(OH)2D3, while plasma Ca2+ after administration of 10 µg 1,25(OH)2D3 increased to 1.31 ± 0.03 mmol/l (p < 0.008). After 72 h, 1α(OH)D3 increased plasma Ca2+ to 1.22 ± 0.02 mmol/l (p < 0.05) and 10 µg 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 1α(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 1α(OH)D3. Plasma phosphate was significantly higher after 1,25(OH)2D3 than after 1α(OH)D3 at 48 (p = 0.016) and 72 h (p < 0.010). Conclusion: A single intravenous dose of both 10 µg 1,25(OH)2D3 and 1α(OH)D3 significantly suppressed plasma PTH. The acute suppressive effect of 1,25(OH)2D3 was 3 times greater than that of 1α(OH)D3. The increase in plasma Ca2+ after intravenous administration of 10 µg of 1,25(OH)2D3 was, however, significantly greater than that of 10 µg of 1α(OH)D3 (p < 0.005). The PTH response to acute administration of 10 µg 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.