Vitamin D metabolism in normal and chronic kidney disease states

Abstract

Vitamin D is a prohormone synthesized in the skin from the precursor molecule 7-dehydrocholesterol by the action of sunlight. It is found in low amounts in food, with fortified dairy and fish oils being the most abundant source. Vitamin D undergoes an important 2-step bio-activation process required to produce the active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2 D). The bio-activation process comprises the synthesis of 25-hydroxyvitamin D in the liver by 25-hydroxylation, followed by the conversion to 1,25(OH)2 D by the 1α-hydroxylase in kidney under very tightly regulated physiological conditions. 1,25(OH)2 D is responsible for maintaining adequate levels of calcium and phosphorus in the blood. Calcium is essential for muscles and nervous system functions, and through the actions of 1,25(OH)2 D on intestine, kidney, and bone, the body prevents imbalances of both calcium and phosphate via an intricate system. In addition, 1,25(OH)2 D plays an important role in many biological non-calcemic functions throughout the body. 1,25(OH)2 D must bind to the vitamin D receptor to carry out its functions. The highly active and lipid soluble 1,25(OH)2 D is inactivated by the 24-hydroxylase, which is the enzyme responsible for the major catabolic pathway that ultimately results in the water soluble calcitroic acid for excretion in the urine. Regulation of key players in vitamin D metabolism is reciprocal and very tight. The activating enzyme 1α-hydroxylase, and the catabolic enzyme 24-hydroxylase are reciprocally regulated by PTH, 1,25(OH)2 D, and FGF23. Chronic kidney disease is associated with abnormalities of phosphorus homeostasis and altered vitamin D metabolism, and if left untreated, result in significant morbidity and mortality.