Suppression of secondary hyperparathyroidism in chronic dialysis patients by single oral weekly dose of 1,25-dihydroxycholecalciferol.
Eleven hemodialysis patients who developed refractory secondary hyperparathyroidism, despite conventional vitamin D therapy, were treated with large oral doses of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. Therapeutic regimen was a single oral dose of up to 8.0 micrograms administered once weekly following hemodialysis. A maximum serum level of 1,25(OH)2D occurred four hours after the 8.0 micrograms dose. A positive correlation (Y = 84.3X-22.1: P < 0.01) was found between the maximal serum 1,25(OH)2D concentration (Cmax) and the dose of 1,25(OH)2D3 when plotted on a logarithmic scale. Forty-eight hours after the administration of the 8.0 micrograms dose, the parathyroid hormone (PTH) level and the alkaline phosphatase activity (ALP) were markedly decreased without evidence of hypercalcemia. A significant inverse relationship was found between the Cmax of 1,25(OH)2D and the percent change in the PTH level measured after 48 hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion assay (HS-PTH). From these results, the level of serum 1,25(OH)2D required to blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these serum levels were achieved by the oral administration of doses of 6.0-8.0 micrograms or higher. There were no adverse effects of treatment. Following this study, one patient was continuously treated with 8.0 micrograms of 1,25(OH)2D3 orally once a week for 18 months. There was a therapeutic effect (as evidenced by PTH suppression, ALP suppression and the disappearance of subjective complaints) without the development of severe hypercalcemia or hyperphosphatemia. This treatment may help to prevent or treat secondary hyperparathyroidism in patients receiving long-term dialysis.
Shigematsu
T
T
Second Department of Medicine, Jikei University School of Medicine, Tokyo.
Kawaguchi
Y
Y
Unemura
S
S
Yamamoto
H
H
Momose
M
M
Yokoyama
K
K
Wakabayashi
Y
Y
Ikeda
M
M
Hasegawa
T
T
Sakai
O
O
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D002117:Calcitriol / Q000008:administration & dosage* / Q000097:blood; D002118:Calcium / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D008274:Magnesium / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects*
D010281:Parathyroid Hormone; D010758:Phosphorus; D000469:Alkaline Phosphatase; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium