Role of the Calcium-Sensing Receptor in Reducing the Risk for Calcium Stones

Abstract

The tight control of blood Ca2+ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca2+. It is the concerted action of intestine, bone, and kidney that controls the Ca2+ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca2+, respectively. Along the nephron, fine-tuning of blood Ca2+ levels takes place by Ca2+ reabsorption. The calciotropic hormones regulate Ca2+ transport processes, leading to whole-body Ca2+ homeostasis and, importantly, preserving a constant Ca2+ concentration in the blood. Defects in renal Ca2+ handling can lead to hypercalciuria, consecutive kidney stone formation, and obstructive nephropathy. Here we give an overview of the key players involved in normal Ca2+ management and describe the in-depth investigations on a renal hypercalciuric model of disease, the Trpv5 knockout mouse, which naturally displays molecular adaptations that prevent Ca2+ precipitation in the kidney.