EFFICACY AND SAFETY OF INTERMITTENT ORAL 1-ALPHA(OH) VITAMIN-D-2 IN SUPPRESSING 2-DEGREES HYPERPARATHYROIDISM IN HEMODIALYSIS-PATIENTS

Calcitriol has a low therapeutic index for the treatment of 2 degrees hyperparathyroidism (HPT) in hemodialysis (HD) patients. In an earlier protocol (Protocol 1), the vitamin D analog, 1 alpha-hydroxyvitamin D -2 1 alpha D-2), was effective in lowering serum intact PTH (iPTH) in HD patients with 2 degrees HPT (iPTH >400 pg/ml) without significant h ypercalcemia or hyperphosphatemia; most patients received 4 mu g daily (28 mu g/week), and a few received 4 mu g after each dialysis session (3 times/week). The present protocol (Protocol 2) evaluated the effec tiveness and safety of the same starting dose of 10 mu g per HD in all patients (30 mu g/week). Ten patients who had completed Protocol 1 wi th a dose of 4 mu g daily (6 patients) or 4 mu g three times a week af ter HD (4 patients) completed Protocol 2. Nine men and 1 woman-ages 27 to 72 years who were dialyzed for between 4 to 116 months-were treate d. After a washout period of 8 weeks, 1 alpha D-2 was given for 12 wee ks or until iPTH fell below 100 pg/ml. Temporary stop points were a se rum phosphorus (P) >8.0 mg/dl or serum calcium (Ca) > 11.4 mg/dl; trea tment was resumed at a lower dose when Ca fell to less than or equal t o 10.2 mg/dl or P fell to less than or equal to 6.9 mg/dl. Only Ca-bas ed phosphorus binders were used. For the 6 patients treated with 4 mu g/day 1 alpha D-2 in Protocol 1 and later with 10 mu g/3 times a week in Protocol 2, the iPTH decreased from a baseline of 893 +/- 100 pg/ml to a nadir of 215 +/- 67 pg/ml, and from 879 +/- 118 pg/ml to 217 +/- 76 pg/ml, respectively. In Protocol 1, the baseline serum Ca rose fro m 8.97 +/- 0.31 mg/dl to 9.67 +/- 0.27 mg/dl at the iPTH nadir, and in Protocol 2 from 8.78 +/- 0.18 mg/dl to 9.95 +/- 0.26 mg/dl. For the 4 patients treated in Protocol 1 with 1 alpha D-2 4 mu g/3 times a week and later with 10 mu g/3 times a week, the baseline iPTH fell from 48 4 +/- 40 pg/ml to a nadir of 160 +/- 22 pg/ml, and from 537 +/- 60 pg/ ml to 108 +/- 35 pg/ml, respectively. The serum Ca rose from 8.66 +/- 0.32 mg/dl at baseline to 9.58 +/- 0.45 at iPTH nadir and from 8.66 +/ - 0.18 mg/dl to 9.23 +/- 0.39 mg/dl in the first and second protocols, respectively. Serum P levels at baseline and the nadir did not differ with either protocol. Thus, intermittent ''high'' doses of 1 alpha D- 2 are as effective as a similar total dose given daily, both treatment s ave associated with mild increases in the serum Ca but no change in serum P. Dosing with the dialysis procedure offers the advantage of gr eater compliance, and the therapeutic index of 1 alpha D-2 appears rel atively high with both regimens.