Calcitriol, as used for treating secondary hyperparathyroidism, has a low therapeutic index. The safety and efficacy of the vitamin D analog, 1 alpha (OH)-vitamin D2, (1 alpha D2), which has less toxicity in animals than 1 alpha (OH)-vitamin D3, was tested in a multicenter study of 24 hemodialysis patients with secondary hyperparathyroidism [serum intact (i) PTH > 400 pg/ml]. Calcium-based phosphate binders alone were used to maintain serum phosphorus < or = 6.9 mg/dl. After eight weeks without calcitriol (washout), oral 1 alpha D2, 4 micrograms/day or 4 micrograms thrice weekly, was started, with the dose adjusted over 12 weeks to maintain serum iPTH between 130 and 250 pg/ml. Pre-treatment serum iPTH fell from 672 +/- 70 pg/ml (SEM) to 289 +/- 36 after treatment (P < 0.05). The maximal decrease in serum iPTH was 48 to 96%, with 87.5% of patients reaching target iPTH levels. The final dose of 1 alpha D2 average 14.2 micrograms/week. Pre-treatment serum calcium rose modestly from 8.8 +/- 0.2 mg/dl to 9.5 +/0 0.2 after treatment (P < 0.001). Only once did modest hypercalcemia (serum Ca > 11.2 mg/dl) necessitate stopping treatment. Neither the average serum P level, the incidence of hyperphosphatemia, nor the dose of phosphate binders changed from washout to treatment. Thus, oral 1 alpha D2 is highly efficacious in suppressing secondary hyperparathyroidism in hemodialysis patients and is safe despite exclusive use of calcium-based phosphate-binders. Future studies should clarify the optimal dosage regimen.

Calcitriol is effective in suppressing PTH levels in haemodialysis patients with hyperparathyroidism but has a low therapeutic index. There is a search for other vitamin D sterols that suppress PTH but cause less hypercalcaemia. We review evidence that 1 alpha-hydroxy-vitamin D2 (1 alpha-D2) may be an effective and safer alternative to calcitriol. In vitamin D-deficient rats, 1 alpha-D2 is equipotent to 1 alpha-D3, which is converted to calcitriol before it acts; but, in normal rats, 1 alpha-D2 is much less toxic at high doses. In osteopenia models, either steroid-induced or following ovariectomy, 1 alpha-D2 is equal to or more effective than 1 alpha-D3 in preventing bone loss but causes less hypercalciuria. Studies in osteoporotic women reveal minimal hypercalciuria with 1 alpha-D2 at doses up to 4 micrograms/day, data suggesting greater safety than reported with calcitriol or 1 alpha-D3. Preliminary data in haemodialysis patients with secondary hyperparathyroidism demonstrate the efficacy of 1 alpha-D2 in suppressing PTH levels with minimal untoward effects on serum Ca and no effects on serum P. Taken together, these observations suggest that 1 alpha-D2 deserves strong consideration as a therapeutic agent for secondary hyperparathyroidism associated with end-stage renal disease.

Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis.