1.25- Dihydroxyvitamin renal disease

In chronic renal disease, the kidney fails to produce enough or any of the 25-hydroxy-la-hydroxylase enzyme that converts 25-hydroxy vitamin D3 to the circulating hormonal form, la,25-dihydroxyvitamin D3. Biochemical and bone abnormalities have been corrected with doses of la-hydroxy- or la,25-dihydroxyvitamin D3 of 1 pg daily. 

Vitamin D and its metabolites play an important role in the maintenance of extracellular calcium concentrations and in normal skeletal structure and mineralization. Vitamin D is necessary for the optimal absorption of calcium and phosphorus. On a worldwide basis, the most common cause of hypocalcemia is nutritional vitamin D deficiency. In malnourished populations, manifestations include rickets and osteomalacia. Nutritional vitamin D deficiency is uncommon in Western societies because of the fortification of miUc with ergocalciferol. " The most common cause of vitamin D deficiency in Western societies is gastrointestinal disease. Gastric surgery, chronic pancreatitis, small-bowel disease, intestinal resection, and bypass surgery are associated with decreased concentrations of vitamin D and its metabolites. Vitamin D replacement therapy may need to be administered by the intravenous route if poor oral bioavailability is noted. Decreased production of 1,25-dihydroxyvitamin D3 may occur as a result of a hereditary defect resulting in vitamin D-dependent rickets. It also can occur secondary to chronic renal insufficiency if there is insufficient production of the 1 -a -hydroxylase enzyme for the... 

Nogawa K, Tsuritani I, Kido T, Honda R, Yamada Y, Ishizaki M. Mechanism for bone disease found in inhabitants environmentally exposed to cadmium decreased serum 1a,25-dihydroxyvitamin D level. Int Arch Occup Environ Health 1987 59 21-30. Nogawa K, Kobayashi E, Yamada Y, Honda R, Kido T, Tsuritani I. Ishizaki M. Parathyroid hormone concentration in the serum of people with cadmium-induced renal damage. Int Arch Occup Environ Health 1984 54 187-193. 

The advances in our understanding of vitamin D3 metabolism which have been described in the previous sections have promoted the rapid use of some of these compounds in the clinic. Both la-hydroxyvitamin D3 and la,25-dihydroxyvitamin D3 have been studied in several disease states, such as chronic renal failure 28, 32, 33, 51, 71, 115, 144), hypoparathyroidism 74, 159), osteomalacia 23, 87), osteoporosis 106), and neonatal hypocalcemia 47,96). 

---