Calcium-sensing receptor (CaSR)

Class

Calcimimetic

Pathway

Parathyroid hormone (PTH) / calcium-sensing receptor axis — treatment of secondary hyperparathyroidism in CKD dialysis patients

The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor expressed mainly on parathyroid chief cells, where it continuously monitors the concentration of calcium in blood. When calcium binds CaSR, the receptor sends an intracellular signal that reduces secretion of parathyroid hormone (PTH), the hormone that raises blood calcium by acting on bone, kidney, and intestine. In chronic kidney disease, phosphate retention and reduced activation of vitamin D lead to persistently low or dysregulated calcium signaling, driving parathyroid gland enlargement and excessive PTH release—a condition called secondary hyperparathyroidism. Left uncontrolled, this contributes to bone weakening, vascular calcification, and cardiovascular complications, particularly in patients undergoing dialysis. Calcimimetic drugs are small molecules that bind CaSR and increase its sensitivity to existing calcium levels, effectively amplifying the natural feedback signal without requiring higher blood calcium itself. This lowers PTH secretion and helps normalize the parathyroid-calcium-phosphate axis. Because CaSR also functions in the kidney and other tissues, modulating it has effects beyond the parathyroid gland, making calcium balance a central consideration in how these agents are used. This mechanism is broadly relevant wherever excess PTH activity threatens bone and cardiovascular health in the setting of impaired kidney function.