Vitamin D metabolism and stones

Abstract

It has been nearly 90 years since the discovery of the antirachitic activity of vitamin D. During that period, vitamin D structure, metabolism, and mechanism of action at target tissues have been delineated. We now recognize that vitamin D acts as a steroid hormone to help maintain normal calcium and phosphate homeostasis. Many diseases characterized by deranged calcium and phosphate metabolism have been explained by dysregulated vitamin D production and/or action. Calcium-containing kidney stones are believed to result from excessive urinary calcium excretion due to increased intestinal absorption of calcium, increased bone resorption, and renal calcium loss. To try and explain the cause of this hypercalciuria, many studies have focused on the role of deranged vitamin D metabolism and action. Much of our understanding of how such derangements in vitamin D metabolism and action can contribute to the development of hypercalciuria and ultimately kidney stones has come from both clinical and basic approaches that are discussed in this chapter. However, some studies have failed to observe any alteration in vitamin D production or action, while others have implicated a role for increased 1,25(OH)2D production or increased tissue sensitivity in the face of normal circulating 1,25(OH)2D concentrations. Resolution of these discrepancies will require additional studies in hypercalciuric stone-forming patients that focus on the genetics of vitamin D metabolism and the cellular and molecular actions of vitamin D at its target tissues. © 2011 Springer-Verlag London Limited.