Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses.

Background/aims: Although the PTH-suppressive effect of intravenous calcitriol has already been demonstrated by various studies, the precise dose-response to calcitriol has not been fully determined for uremic secondary hyperparathyroidism (2HPT). In order to investigate in detail the dose-response of intravenous calcitriol and the adequate initial dose against 2HPT, a randomized prospective double-blind study was conducted.

Method: One-hundred and sixty-two patients with 2HPT undergoing hemodialysis three times per week were randomly assigned to four calcitriol (Ro21-5535) treatment groups, 0 (placebo), 1, 1.5 or 2 microg. Calcitriol or placebo was given intravenously after each dialysis for 12 weeks under double-blind conditions.

Results: Calcitriol dose-dependently reduced both intact-PTH and high-sensitivity assay mid-terminal (HS)-PTH levels. The rate of per-week change in intact-PTH was 0.0% in the placebo group, -7.8% in the 1-microg group, -18.9% in the 1.5-microg group and -24.1% in the 2-microg group. Calcitriol dose-dependently increased the rate of increase in serum Ca adjusted by albumin level. The per-week increases in adjusted serum Ca were -0.01, 0.08, 0.23 and 0.35 mg/dl in the placebo, 1-, 1.5- and 2-microg groups, respectively. Although the degree of PTH suppression was correlated with the adjusted serum Ca increase, by-patients investigation revealed that the number of patients with suppression of PTH despite of no or slight elevation of adjusted serum Ca level was largest in the 1-microg group among the three calcitriol groups.

Conclusion: Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.