Action of 1,25-Dihydroxycholecalciferol, a Potent, Kidney-Produced Metabolite of Vitamin D3, in Uremic Man

Abstract

Only the kidney is capable of producing 1,25-dihydroxycholecalciferol (1,25diOHC), the probable active form of vitamin D. The possibility that parenchymal damage in chronic renal disease impairs production of 1,25diOHC and accounts for "vitamin-D-resistant" uremia prompted our evaluation of its effect in uremic man. Three patients with advanced renal failure showed significant responses to daily treatment with only 100 U (2.7 μg) of 1,25diOHC for six to 10 days: serum calcium and phosphorus rose; intestinal radioactive calcium (⁴⁷Ca) absorption increased by 30 to 220 per cent; and fecal calcium decreased by 25 to 71 per cent in those undergoing balance studies. In contrast, 40,000 U (1 mg) of vitamin D₃ caused no change in serum calcium and phosphorus and had negligible effects on ⁴⁷Ca absorption. Thus, 1,25diOHC is highly active in uremic man, and its impaired production may account for certain abnormalities of calcium homeostasis in uremia. The agent may hold future promise in management of disordered calcium metabolism in uremia.