The Role of the Calcium-Sensing Receptor in the Pathophysiology of Secondary Hyperparathyroidism

The calcium-sensing receptor (CaR), a seven-transmembrane domain receptor belonging to the G protein-coupled receptor family, is responsible for calcium-mediated signalling initiated at the surface of parathyroid cells that controls the synthesis and secretion of parathyroid hormone (PTH). Expression of the CaR is downregulated in animal models of uraemia and in patients with secondary hyperparathyroidism (SHPT). Cinacalcet is a type II calcimimetic agent that acts as an allosteric modulator of CaR signalling. It has been shown in clinical studies to improve control of serum PTH levels and in preclinical studies to attenuate SHPT disease progression and parathyroid hyperplasia. Cinacalcet represents the first of this novel class of agents and a major advance in the treatment of SHPT.