SUPPRESSION OF SECONDARY HYPERPARATHYROIDISM IN CHRONIC DIALYSIS PATIENTS BY SINGLE ORAL WEEKLY DOSE OF 1,25-DIHYDROXYCHOLECALCIFEROL

Eleven hemodialysis patients who developed refractory secondary hyperp arathyroidism, despite conventional vitamin D therapy, were treated wi th large oral doses of 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. Th erapeutic regimen was a single oral dose of up to 8.0 mug administered once weekly following hemodialysis. A maximum serum level of 1,25(OH) 2D occurred four hours after the 8.0 mug dose. A positive correlation (Y=84.3X-22.1: P<0.01) was found between the maximal serum 1,25(OH)2D concentration (Cmax) and the dose of 1,25(OH)2D3 when plotted on a log arithmic scale. Forty-eight hours after the administration of the 8.0 mug dose, the parathyroid hormone (PTH) level and the alkaline phospha tase activity (ALP) were markedly decreased without evidence of hyperc alcemia. A significant inverse relationship was found between the Cmax of 1,25(OH)2D and the percent change in the PTH level measured after 48 hours, either with carboxy-terminal (C-PTH) or the highly sensitive mid-portion assay (HSPTH). From these results, the level of serum 1,2 5(OH)2D required to blunt the rise in serum PTH was 168 pg/ml and 203 pg/ml, respectively; these serum levels were achieved by the oral admi nistration of doses of 6.0-8.0 mug or higher. There were no adverse ef fects of treatment. Following this study, one patient was continuously treated with 8.0 mug of 1,25(OH)2D3 orally once a week for 18 months. There was a therapeutic effect (as evidenced by PTH suppression, ALP suppression and the disappearance of subjective complaints) without th e development of severe hypercalcemia or hyperphosphatemia. This treat ment may help to prevent or treat secondary hyperparathyroidism in pat ients receiving long-term dialysis.