Effect of Intravenous 1-Alpha-Hydroxyvitamin D₃ on Secondary Hyperparathyroidism in Chronic Uremic Patients on Maintenance Hemodialysis

Abstract

The effect of intravenous 1α(OH)D₃ on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1α(OH)D₃ under careful control of serum Ca²⁺. 1α(OH)D₃ was given intravenously at doses of up to 4 μg three times a week, and blood samples were obtained every week, including 1 week before treatment (basal control). No patients were treated with oral vitamin D metabolites. At the end of the study intact PTH levels were reduced by an average of 67 ± 6%, and COOH-terminal immunoreactive PTH levels were reduced by 35 ± 6%. Serum Ca²⁺ was kept within normal levels, but showed a slight increase from 1.17 to 1.30 rnmol/l. An effect of calcium on PTH secretion could not be excluded, but an effect of 1α(OH)D₃, independent of serum Ca²⁺ was also found. This effect may be mediated by 1,25(OH)₂D₃, assuming a large capacity of the 25-hydroxylase in the liver to convert 1α(OH)D₃ to 1,25(OH)₂D₃. Also, the parathyroid glands may possess receptors for 1α(OH)D₃ with an effect similar to that established for the 1,25(OH)₂D₃ receptors. Thus, although the exact mechanisms ofthe action of 1α(OH)D₃ have not yet been completely clarified, it is concluded that intravenous administration of 1α(OH)D₃ may be of benefit in the treatment of secondary hyperparathyroidism of uremia.

Long-Term Suppression of Secondary Hyperparathyroidism by Intravenous 1α-Hydroxy vitamin D₃ in Patients on Chronic Hemodialysis

“…Our laboratory has previously published results from a study on intravenous administration of la(OH)D3 for 12 weeks to patients on chronic hemodialysis [11], We found a marked suppression of the intact PTH (PTH 1-84) secretion and only a slight increase in plasma Ca2+, which alone could not explain the decrease in PTH concentra tions. The aim of the present investigation, therefore, was to examine whether it was possible to maintain a long term marked suppression of PTH secretion by a contin uous use of intravenous administration of la(OH)D3 to patients with severe secondary hyperparathyroidism on chronic hemodialysis.…”

“…Rigshospitalct, Copenhagen, were included in the present study of which the preliminary results of the first 12 weeks of treatment with 1 a(OH)Dj previously have been published [11]. Nine patients were withdrawn from the study after 12 weeks of treatment due to: severe hypercalcemia (n = 1 ), death due to myocar dial infarction (n = 1 ), transferred to CAPD (n = 1 ).…”

Can Hyperparathyroid Bone Disease Be Arrested or Reversed?

“…Several clinical studies have documented that PTH levels can be suppressed in most uremic patients and that this suppression can be maintained by continuous treatment with phosphate binders, vitamin D analogs, or calcimimetics (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). PTH levels return to pretreatment values, however, when the treatment is stopped (32,33,37).…”

Intravenous 1,25(OH)2 Vitamin D3 Therapy in Haemodialysis Patients: Evaluation of Direct and Calcium-Mediated Short-Term Effects on Serum Parathyroid Hormone Concentration

“…administered 1,25(OH) 2 D3 on PTH, as recently suggested by Slatopolsky et al [17]. In contrast to this opinion Brandi et al [18] showed a suppression of PTH with i.v. 1-a-hydroxyvitamin D3 despite a marked increase of serum phosphorus; the suppression of PTH, however, was accompanied by a marked increase in the serum calcium concentration.…”