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


METHODS
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.


CONCLUSIONS
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.
Koshikawa
S
S
Fujigaoka Hospital, Showa University, Yokohama, Japan.
Akizawa
T
T
Kurokawa
K
K
Marumo
F
F
Sakai
O
O
Arakawa
M
M
Morii
H
H
Seino
Y
Y
Ogata
E
E
Ohashi
Y
Y
Akiba
T
T
Tsukamoto
Y
Y
Suzuki
M
M
D000328:Adult; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D002120:Calcium Channel Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D011446:Prospective Studies; D012044:Regression Analysis; D006435:Renal Dialysis; D014511:Uremia / Q000150:complications*
D002120:Calcium Channel Agonists; D010281:Parathyroid Hormone; D002117:Calcitriol; D002118:Calcium