Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism.
Calcitriol, as used for treating secondary hyperparathyroidism, has a low therapeutic index. The safety and efficacy of the vitamin D analog, 1 alpha (OH)-vitamin D2, (1 alpha D2), which has less toxicity in animals than 1 alpha (OH)-vitamin D3, was tested in a multicenter study of 24 hemodialysis patients with secondary hyperparathyroidism [serum intact (i) PTH > 400 pg/ml]. Calcium-based phosphate binders alone were used to maintain serum phosphorus < or = 6.9 mg/dl. After eight weeks without calcitriol (washout), oral 1 alpha D2, 4 micrograms/day or 4 micrograms thrice weekly, was started, with the dose adjusted over 12 weeks to maintain serum iPTH between 130 and 250 pg/ml. Pre-treatment serum iPTH fell from 672 +/- 70 pg/ml (SEM) to 289 +/- 36 after treatment (P < 0.05). The maximal decrease in serum iPTH was 48 to 96%, with 87.5% of patients reaching target iPTH levels. The final dose of 1 alpha D2 average 14.2 micrograms/week. Pre-treatment serum calcium rose modestly from 8.8 +/- 0.2 mg/dl to 9.5 +/0 0.2 after treatment (P < 0.001). Only once did modest hypercalcemia (serum Ca > 11.2 mg/dl) necessitate stopping treatment. Neither the average serum P level, the incidence of hyperphosphatemia, nor the dose of phosphate binders changed from washout to treatment. Thus, oral 1 alpha D2 is highly efficacious in suppressing secondary hyperparathyroidism in hemodialysis patients and is safe despite exclusive use of calcium-based phosphate-binders. Future studies should clarify the optimal dosage regimen.
Tan
A U
AU
Medical Service, West Los Angeles Veterans Affairs Medical Center (Wadsworth Division), California, USA.
Levine
B S
BS
Mazess
R B
RB
Kyllo
D M
DM
Bishop
C W
CW
Knutson
J C
JC
Kleinman
K S
KS
Coburn
J W
JW
D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage*; D006934:Hypercalcemia / Q000097:blood / Q000188:drug therapy; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood; D006435:Renal Dialysis
D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; C008088:alfacalcidol