Effective suppression of parathyroid hormone by 1α-hydroxy-vitamin D2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism

Effective suppression of parathyroid hormone by 1α-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, 1α(OH)-vitamin D2 (1αD2), which has less toxicity in animals than 1α(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 ≤ 6.9 mg/dl. After eight weeks without calcitriol (washout), oral 1αD2,4 µg/day or 4 µg 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 1α:D2 averaged 14.2 µg/week. Pre-treatment serum calcium rose modestly from 8.8 ± 0.2 mg/dl to 9.5 ± 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 1αD2 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