SUPPRESSION OF PARATHYROID-HORMONE SECRETION IN HEMODIALYSIS-PATIENTSBY A NOVEL VITAMIN-D ANALOG - 19-NOR-1,25-DIHYDROXYVITAMIN D-2

In this double-blind, placebo-controlled, randomized, multicenter stud y, 35 patients with end-stage renal disease undergoing maintenance hem odialysis were treated three times weekly for 4 weeks with either 19-n or-1,25-dihydroxyvitamin D-2 (paricalcitol) intravenously at doses ran ging from 0.04 to 0.24 mu g/kg or placebo. Eligible patients with seco ndary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] leve l > 300 pg/mL) were initially withdrawn from any existing vitamin D th erapy over a 4-week washout period and then randomized to treatment fo r 4 weeks with either paricalcitol or placebo. Overall, there was a cl inically and statistically significant reduction in iPTH level for pat ients receiving paricalcitol compared with placebo (P = 0.006), The st udy end point for efficacy was at least a 30% reduction from maximum b aseline in iPTH level for 75% of the patients receiving paricalcitol p er dosing group. The study end point for efficacy was at least a 30% r eduction from maximum baseline in iPTH for 75% of patients receiving p aricalcitol per dosing group. Sixty-eight percent (15 of 22) of patien ts receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 mu g/kg), Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups re ceiving 0.16- and 0.24-mu g/kg dosages attained the efficacy end point . Only two patients receiving placebo attained the iPTH end point. The re were no clinically relevant differences in serum calcium (Ca) or ph osphorus (P) levels between the group treated with paricalcitol and th at treated with placebo. Although there was a statistically significan t difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the fina l-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625), On ly one patient treated with paricalcitol developed hypercalcemia befor e or coincident with the iPTH end point. Three other patients receivin g paricalcitol experienced elevated serum Ca levels subsequent to reac hing the iPTH end point, with iPTH reductions of 83% to 98%. There wer e no significant differences between patients treated with paricalcito l and patients treated with placebo in adverse reactions. These result s show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT. (C) 1998 by the National Ki dney Foundation, Inc.