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. Clin J Am Soc Nephrol 6: 2076-2082, 2011. doi: 10.2215/CJN.00480111