Role of the calcium-sensing receptor in reducing the risk for calcium stones

The tight control of blood Ca ²⁺ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca ²⁺. It is the concerted action of intestine, bone, and kidney that controls the Ca ²⁺ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca ²⁺, respectively. Along the nephron, fine-tuning of blood Ca ²⁺ levels takes place by Ca ²⁺ reabsorption. The calciotropic hormones regulate Ca ²⁺ transport processes, leading to whole-body Ca ²⁺ homeostasis and, importantly, preserving a constant Ca ²⁺ concentration in the blood. Defects in renal Ca ²⁺ handling can lead to hypercalciuria, consecutive kidney stone formation, and obstructive nephropathy. Here we give an overview of the key players involved in normal Ca ²⁺ 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 Ca ²⁺ precipitation in the kidney.