1,25-dihydroxyvitamin D (1,25[OH]2D) is the active, hormonal form of vitamin D. It is produced from its precursor (vitamin D) by two hydroxylation steps in the liver and the kidneys. Circulating 1,25(OH)2D levels are regulated by serum calcium and phosphate concentrations, this is mediated by the calcium-regulating hormones, parathyroid hormone (PTH) and phosphate-regulating hormone, fibroblast growth factor-23 (FGF-23). In the human body, 1,25(OH)2D has a broad range of actions which include endocrine, autocrine and paracrine properties. Due to its picomolar concentrations and its lipophilic nature, 1,25(OH)2D is a difficult analyte and represents a challenge to the analytical biochemist with respect to quantification. Until recently, relatively large sample volumes and extensive purification and separation steps were required to quantify 1,25(OH)2D.
The clinical relevance of circulating 1,25(OH)2D is underappreciated. Besides the well-known suppression of circulating 1,25(OH)2D in chronic kidney disease, evidence is accumulating that circulating 1,25(OH)2D is also reduced in other diseases. In addition, several studies have demonstrated that circulating 1,25(OH)2D is inversely associated with clinical outcome and may complement or substitute traditional laboratory tests. Nevertheless, in the clinical setting there are still several gaps in the present knowledge on circulating 1,25(OH)2D. These gaps include incomplete data about the effect of activated vitamin D or the influence of dosing and initial 25OHD level on circulating 1,25(OH)2D; and the effect of different diseases on circulating 1,25(OH)2D.
In conclusion, circulating 1,25(OH)2D is less tightly regulated than assumed and may become a reliable predictor of clinical outcomes in some conditions.