Calcimimetics: a remedy for all problems of excess parathyroid hormone activity in chronic kidney disease?

Cinacalcet is a calcimimetic agent that is now available for use clinically to manage secondary hyperparathyroidism among patients undergoing dialysis regularly. It acts as an allosteric activator of the calcium-sensing receptor, the molecular mechanism that controls parathyroid hormone secretion. This mechanism of action differs fundamentally from that of the vitamin D sterols, which heretofore have been the only definitive pharmacological intervention for treating secondary hyperparathyroidism.

The ability of calcimimetic agents to enhance signaling through the calcium-sensing receptor in parathyroid cells affects several important components of parathyroid gland function. Results from several large clinical trials demonstrate that cinacalcet effectively lowers plasma parathyroid hormone levels in dialysis patients with secondary hyperparathyroidism when used either alone or together with vitamin D. Unlike the vitamin D sterols, which generally raise serum calcium and phosphorus levels, treatment with cinacalcet is associated with modest reductions in serum calcium and phosphorus concentrations. The impact of these biochemical changes on renal bone disease and on soft-tissue and vascular calcification during long-term treatment has yet to be characterized fully. Cinacalcet also diminishes parathyroid hormone gene expression, and studies in experimental animals indicate that its use retards the progression of parathyroid gland hyperplasia and increases bone mass. If confirmed in future clinical trials in patients with secondary hyperparathyroidism, these features represent potentially important ancillary therapeutic benefits.

Calcimimetic agents have diverse effects on parathyroid gland function that may enhance the overall medical management of secondary hyperparathyroidism in patients undergoing dialysis regularly.