Intermittent oral 1alpha-hydroxyvitamin D2 is effective and safe for the suppression of secondary hyperparathyroidism in haemodialysis patients. 1alphaD2 Study Group.

Calcitriol and alfacalcidol are useful in suppressing parathyroid hormone (PTH) in haemodialysis patients, but hypercalcaemia and hyperphosphataemia are frequent. The vitamin D analogue, 1alpha-hydroxyvitamin D2 (1alphaD2), has a higher therapeutic index in animal models. Previously, 1alphaD2, 4 microg/day or 4 microg/haemodialysis, lowered iPTH to the target range in 87.5% of 24 haemodialysis patients with moderate to severe secondary hyperparathyroidism (plasma iPTH, 359-1521 pg/ml). The incidences of hypercalcaemia (serum Ca>2.8 mM) or hyperphosphataemia (serum P>2.23 mM) were low. Later, 10 of these patients were re-treated with 1alphaD2, initial dose, 10 microg, thrice weekly with haemodialysis. The iPTH was suppressed as readily, and there was no greater incidence of hypercalcaemia and hyperphosphataemia. Based on these data, a large, multicentre study is ongoing in California and Tennessee/Mississippi, using 1alphaD2 in haemodialysis patients with iPTH >400 pg/ml. In this and the earlier studies, only calcium-based phosphate binders were used to control serum phosphorus. The initial dose, 10 microg thrice weekly with haemodialysis, is adjusted to maintain a target iPTH within the range of 150-300 microg/ml; the final dose range is 2.5-20 microg per haemodialysis. The protocol includes 8 weeks of wash-out with no vitamin D, 16 weeks of open label treatment period with 1alphaD2, and finally 8 weeks of randomized double blinded treatment with either continued 1alphaD2 or placebo. Forty two patients from California and 38 from Tennessee/Mississippi have completed 16 weeks of open label treatment. In California, iPTH declined from 832+/-95 pg/ml at baseline to 222+/-71 pg/ml at the nadir and to 477+/-117 pg/ml at week 16 of the treatment. In Tennessee/Mississippi, the iPTH declined from 977+/-65 pg/ml to 286+/-42 pg/ml at the lowest point and to 493+/-79 at the end of the treatment. Plasma iPTH reached or fell below the target range in 84% of the 80 patients completing open treatment. Asymptomatic hypercalcaemia (serum Ca>2.8 mM) increased from 0.3 episodes/100 weeks during wash-out to 3.6 episodes/100 treated weeks in California and from 0 to 3.7 episodes in Tennessee/Mississippi. In California and Tennessee, the episodes of hyperphosphataemia (serum P>2.2 mM) increased from 5.0 and 5.0 episodes per 100 patient/week during wash-out to 10.1 and 10.9 episodes/100 treatment weeks, respectively, with 1alphaD2 treatment. There were no adverse events in association with 1alphaD2 treatment. Thus, oral 1alphaD2 is safe and highly effective for the treatment of secondary hyperparathyroidism.