VITAMIN D

Vitamin D is a fat-soluble vitamin that can be acquired either from diet or from sunlight-induced conversion of epidermal fats. In either case, vitamin D undergoes numerous modifications in various organs, including the kidneys, to become a bioactive hormone. (For an illustration, see Plate 4-67).

Vitamin D synthesis begins when ultraviolet waves in sunlight cause photoisomerization of 7-dehydrocholesterol to vitamin D₃ (cholecalciferol), or when vitamin D₂ (ergocalciferol) or D₃ is ingested and absorbed. Major dietary sources of vitamin D include fatty fish and fortified milk. Because vitamin D is fat soluble, inadequate absorption occurs in fat malabsorption states, such as pancreatic insufficiency or cystic fibrosis.

Vitamins D₂ and D₃ are carried on plasma vitamin D–binding proteins to the liver, where 25-hydroxylase converts them to 25-hydroxyvitamin D [calcidiol, abbreviated as 25(OH)D]. From there, 25(OH)D eventually reaches the kidneys, again on vitamin D–binding proteins. 25(OH)D enters proximal tubular epithelial cells via receptor-mediated endocytosis, where it is converted by 1-α-hydroxylase to 1,25-dihydroxyvitamin D [calcitriol, the bioactive vitamin, abbreviated as 1,25(OH)₂D]. 1-α-hydroxylase is upregulated in the presence of PTH, hypocalcemia, and hypophosphatemia. Another proximal tubular enzyme, known as 24-α-hydroxylase, can synthesize an inactive form of vitamin D known as 24,25-dihydroxyvitamin D. This enzyme is upregulated in the presence of 1,25(OH)₂D, which therefore regulates its own synthesis.

Vitamin D’s major functions are to increase the intestinal reabsorption of calcium and phosphate, to stimulate bone metabolism, and to suppress the release of PTH. As a result, profound bone mineralization defects occur in states of deficiency. Such defects are a major component of the phenomenon known as renal osteodystrophy, which occurs in end-stage renal disease (see Plate 4-70).