Comparison between 1alpha(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.

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.

METHODS

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.

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 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).

CONCLUSION

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.