Intermittent doxercalciferol (1 alpha-hydroxyvitamin D-2) therapy for secondary hyperparathyroidism

Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdr awal in hemodialysis patients with secondary hyperparathyroidism. In short- term trials, doxercalciferol (1 alpha-hydroxyvitamin D-2 [1 alpha D-2]) sup pressed intact parathyroid hormone (iPTH) effectively with minimal increase s in serum calcium and phosphorus (P) levels. This modified, double-blinded , controlled trial examined the efficacy and safety of 1 alpha D-2 use in 1 38 hemodialysis patients with moderate to severe secondary hyperparathyroid ism by using novel dose titration; 99 patients completed the study. Hemodia lysis patients with secondary hyperparathyroidism were enrolled onto this s tudy, consisting of washout (8 weeks), open-label 1 alpha D-2 treatment (16 weeks), and randomized, double-blinded treatment with 1 alpha D-2 or place bo (8 weeks). Oral 1 alpha D-2 was administered at each hemodialysis sessio n, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. B aseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by we ek 1 (P < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to ba seline during placebo treatment but remained suppressed with 1 alpha D-2 tr eatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were requi red in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatme nt, serum calcium levels were slightly greater with 1 alpha D-2 than placeb o, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1 alpha D-2 an d placebo, respectively (P < 0.01); median level was 11.6 mg/dL during hype rcalcemia. Intermittent oral 1 1 alpha D-2 therapy effectively suppresses i PTH in hemodialysis patients with secondary hyperparathyroidism, with accep table mild hypercalcemia and hyperphosphatemia. (C) 2000 by the National Ki dney Foundation, Inc.