Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D-2 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 D-2 (1 alpha D-2), which has less toxicity in animals than 1 alpha(OH)-vitamin D-3, 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 less than or equal to 6.9 mg/dl. After eight weeks without calcitriol (washout), oral 1 alpha D-2, 4 mu g/day or 4 mu g thrice weekly, was started, with thr 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 D-2 averaged 14.2 mu g/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 1 alpha D-2, 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.