Effects on Serum Parathyroid Hormone of Intravenous Treatment with Alphacalcidol in Patients on Chronic Hemodialysis

Abstract

Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidol, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1 and 4 μg/dialysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland’s sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidol is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.

Serum Parathyroid Hormone Suppression by Intravenous 1,25-Dihydroxy vitamin D3 in Patients on Maintenance Haemodialysis

“…Few studies have reported on the use of calcitriol [14,15]. The present study confirms that l,25(OH)2D 3 given intravenously has a pronounced suppressive effect on the release of PTH and normaliza tion of serum calcium levels.…”

“…There was a sup pression of PTH levels before any significant increase in the serum calcium level [14]. Intravenous administration of a-calcidiol, a synthetic analogue which is metabolised to calcitriol, produces the same result [15]. Several inves tigators in uncontrolled studies have found that intrave nous administration of l,25(OH)2D3 is more effective and better tolerated than oral therapy of pharmacological doses [14,16].…”

Prevention of Hyperparathyroidism in Patients on Maintenance Dialysis by Intravenous 1-Alpha-Hydroxyvitamin D₃ in Association with Mg(OH)₂ as Sole Phosphate Binder

“…Medical curative treatment of overt hyperpara thyroidism with subperiosteal resorption and/or increased plasma alkaline phosphatase has been claimed to be im proved by intermittent intravenous administration of la-hydroxylated vitamin D (la-OH-D) metabolites either calcitriol [2,3] or la-hydroxyvitamin D ,(la-O H -D ,) [4,5] which is transformed by the liver into calcitriol after 25-hydroxylation [6]. As a matter of fact, these treatments effectively decreased elevated levels of plasma PTH [2][3][4][5] and alkaline phosphatase [2][3][4] and improved the histological para meters of severe osteitis fibrosa [2] even in patients in whom former treatment with oral calcitriol had been unsuccessful because of recurrent hypercalcemia [2,3].…”

“…Medical curative treatment of overt hyperpara thyroidism with subperiosteal resorption and/or increased plasma alkaline phosphatase has been claimed to be im proved by intermittent intravenous administration of la-hydroxylated vitamin D (la-OH-D) metabolites either calcitriol [2,3] or la-hydroxyvitamin D ,(la-O H -D ,) [4,5] which is transformed by the liver into calcitriol after 25-hydroxylation [6]. As a matter of fact, these treatments effectively decreased elevated levels of plasma PTH [2][3][4][5] and alkaline phosphatase [2][3][4] and improved the histological para meters of severe osteitis fibrosa [2] even in patients in whom former treatment with oral calcitriol had been unsuccessful because of recurrent hypercalcemia [2,3]. The rationale for this possible superiority (which has never been proven by a randomized controlled study of intravenous versus oral administration of la-OH-D metabolites) is that the intrave nous route induces higher plasma concentrations of calcit riol at the parathyroid levels where by activation of the calcitriol receptors they induce a direct suppression of the PTH secretion by decreasing the transcription of the prep roparathormone gene [7], With the same dose of calcitriol administered orally, the plasma levels of calcitriol are lower because calcitriol would be then partially destroyed in the intestine wall and the liver.…”

Relating Change to Initial Value

“…All the references cited are from the same research group, but it is true that many such papers are published. Indeed, at least one further example has subsequently appeared in Nephron [5], This does not make the method correct. Rather, it illustrates my second point, which is that scientific journals should use statisti cal referees to try to reduce (if not eliminate) the misuse of statistics in medical journals.…”