INTERMITTENT ORAL 1-ALPHA-HYDROXYVITAMIN D2 IS EFFECTIVE AND SAFE FORTHE SUPPRESSION OF SECONDARY HYPERPARATHYROIDISM IN HEMODIALYSIS-PATIENTS

Calcitriol and alfacalcidol are useful in suppressing parathyroid horm one (PTH) in haemodialysis patients, but hypercalcaemia and hyperphosp hataemia are frequent, The vitamin D analogue, 1 alpha-hydroxyvitamin D-2 (1 alpha D-2), has a higher therapeutic index in animal models. Pr eviously, 1 alpha D-2, 4 mu g/day or 4 mu g/haemodialysis, lowered iPT H to the target range in 87.5% of 24 haemodialysis patients with moder ate to severe secondary hyperparathyroidism (plasma iPTH, 359-1521 pg/ ml). The incidences of hypercalcaemia (serum Ca > 2.8 mM) or hyperphos phataemia (serum P > 2.23 mM) were low. Later, 10 of these patients we re re-treated with 1 alpha D-2, initial dose, 10 mu g, thrice weekly w ith haemodialysis. The iPTH was suppressed as readily, and there was n o greater incidence of hypercalcaemia and hyperphosphataemia. Based on these data, a large, multicentre study is ongoing in California and T ennessee/Mississippi, using 1 alpha D-2 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 mu g thrice weekly with haemodialysis, is adjusted to maintai n a target iPTH within the range of 150 300 mu g/ml; the final dose ra nge is 2.5-20 mu g per haemodialysis. The protocol includes 8 weeks of wash-out with no vitamin D, 16 weeks of open label treatment period w ith 1 alpha D-2, and finally 8 weeks of randomized double blinded trea tment with either continued 1 alpha D-2 or placebo. Forty two patients from California and 38 from Tennessee/Mississippi have completed 16 w eeks 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 reach ed or fell below the target range in 84% of the 80 patients completing open treatment. Asymptomatic hypercalcaemia (serum Ca > 2.8 mM) incre ased episodes/100 weeks during wash-out to 3.6 episodes/100 treated we eks in California and from 0 to 3.7 episodes in Tennessee/Mississippi. In California and Tennessee, the episodes of hyperphosphataemia (seru m P > 2.2 mM) increased from 5.0 and 5.0 epiodes per 100 patient/week during wash-out to 10.1 and 10.9 episodes/100 treatment weeks, respect ively, with 1 alpha D-2 treatment. There were no adverse events in ass ociation with 1 alpha D-2 treatment. Thus, oral 1 alpha D-2 is safe an d highly effective for the treatment of secondary hyperparathyroidism.