Intermittent oral 1α-hydroxyvitamin D2 is effective and safe for the suppression of secondary hyperparathyroidism in haemodialysis patients

被引:40
作者
Frazao, JM
Chesney, RW
Coburn, JW
机构
[1] W Los Angeles Vet Affairs Med Ctr, Nephrol Sect W111L, Wadsworth Div, Med & Res Serv, Los Angeles, CA 90073 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA
[3] Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Pediat, Memphis, TN 38163 USA
[4] Bone Care Int Inc, Madison, WI USA
关键词
haemodialysis; 1 alpha-hydroxyvitamin D-2; intact PTH; secondary hyperparathyroidism; therapeutic trial; vitamin D;
D O I
10.1093/ndt/13.suppl_3.68
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Calcitriol and alfacalcidol are useful in suppressing parathyroid hormone (PTH) in haemodialysis patients, but hypercalcaemia and hyperphosphataemia are frequent, The vitamin D analogue, 1 alpha-hydroxyvitamin D-2 (1 alpha D-2), has a higher therapeutic index in animal models. Previously, 1 alpha D-2, 4 mu g/day or 4 mu g/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 1 alpha D-2, initial dose, 10 mu g, 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 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 maintain a target iPTH within the range of 150 300 mu g/ml; the final dose range 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 with 1 alpha D-2, and finally 8 weeks of randomized double blinded treatment with either continued 1 alpha D-2 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 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 epiodes per 100 patient/week during wash-out to 10.1 and 10.9 episodes/100 treatment weeks, respectively, with 1 alpha D-2 treatment. There were no adverse events in association with 1 alpha D-2 treatment. Thus, oral 1 alpha D-2 is safe and highly effective for the treatment of secondary hyperparathyroidism.
引用
收藏
页码:68 / 72
页数:5
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