Vitamin D, the kidney and calcium homeostasis

In 1919 Sir Edward Mellanby produced experimental rickets for the first time and reported on its subsequent cure and prevention with cod liver oil. Within the next six years, Steenbock and associates discovered that antirichitic activity could be produced in animals and food by ultraviolet irradiation. During the 1920's and 1930's accelerated interest in this "antirichitic activity" led to the synthesis of the natural provitamin, 7-dehydrocholesterol, and ultimately to the isolation and identification of vitamin D [1]. In the last 20 years, vitamin D has been shown to play a pivotal role in the biochemical control of intestinal calcium absorption and bone remodeling. Of utmost significance was the discovery that vitamin D in itself was inert and that metabolic activation was essential to its biological expression. Today, in fact, the term "vitamin" D is a misnomer for all practical purposes since its endogenous production by the skin, distribution by the blood stream, the negative feedback control of its metabolism, and its mode of action through the stimulation of protein synthesis, all resemble hormonal rather than dietary vitamin activity. Intermediary metabolism of vitamin D. Within the last decade, considerable knowledge has accumulated regarding the metabolism of vitamin D and its biological activity in health and disease. In man, ultraviolet irradiation isomerizes 7-dehydrocholesterol in skin to vitamin D3 resulting in an average vitamin D3 content of approximately 3.2 g/g tissue or 17 lU/cm2 of skin [2]. The preformed vitamin D3 is then absorbed into the micro-circulation and transported in plasma while bound to a specific globulin of d> 1.21 and a molecular weight of approximately 60,000 [3, 4]. Dietary vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) are absorbed bound to lipoproteins primarily from the duodenum and jejunum into lymphatic channels with both bile salts as well as intestinal lipids permissive in this regard [5]. The absorbed vitamin D2 or D3 then admixes with endogenously synthesized vitamin D3 and is either sequestered in storage depots or metabolically transformed. Adipose tissue and muscle appear to be major storage sites for vitamin D3 [6, 7], presumably serving as a source of the vitamin during dietary deprivation and/or lack of sunlight exposure. Circulating vitamin D3 levels, as determined by gas-liquid chromatographic techniques [8] in subjects on routine diets, normally range between 8 and 45 ng/ml; at this plasma level, vitamin D3 disappears with