Vitamin D3 is converted by a liver enzyme system, calciferol-25-hydroxylase, to 25-hydroxycholecalciferol (25-HCC), the active hormonal form of the vitamin. This hydroxylase is feedback inhibited by 25-HCC, and probably represents an important physiologic control step for active vitamin D. The 25-HCC is further converted in intestine, kidney, and bone to two more polar metabolites which probably represent the metabolically active form of vitamin D3. Evidence has been presented that in uremia, excessive metabolism of vitamin D results in low plasma levels of 25-HCC. In chronically uremic rats, 25-HCC is at least one hundredfold more effective than vitamin D3 in restoring calcium absorption. In uremics, treatment with 10,000 international units (IU) of 25-HCC/day, improves calcium absorption, increases urinary and plasma calcium and decreases plasma alkaline phosphatase. Thus, 25-HCC may be the drug of choice in bone disease of uremia.
DeLuca HF, Avioli LV. Treatment of Renal Osteodystrophy With 25-Hydroxycholecalciferol. Arch Intern Med. 1970;126(5):896–899. doi:10.1001/archinte.1970.00310110166030