Calcimimetic agents for the treatment of secondary hyperparathyroidism.

Calcimimetic agents function as allosteric activators of the calcium-sensing receptor (CaSR). In parathyroid tissue, they decrease the threshold for CaSR activation by extracellular calcium ions and diminish parathyroid hormone (PTH) secretion directly. Results from small clinical studies in hemodialysis patients with secondary hyperparathyroidism have shown that single oral doses of calcimimetic compounds abruptly decrease plasma PTH levels within 1 to 2 hours in a dose-dependent manner. Sustained decreases in plasma PTH levels can be achieved when daily oral doses are given for as long as 18 weeks. Decreases in plasma PTH levels often are associated with modest decreases in serum calcium and phosphorus levels, but symptomatic hypocalcemia is uncommon. Data gathered during larger more recent clinical trials lasting 12 to 24 months again indicate that plasma PTH levels can be decreased effectively with persistent and favorable decreases in serum phosphorus levels and in values for the calcium-phosphorus ion product in serum. Calcimimetic agents thus offer a novel treatment for secondary hyperparathyroidism in patients with chronic kidney disease stage 5, who are managed with dialysis. Unlike the vitamin D sterols, calcimimetic compounds effectively decrease plasma PTH levels without aggravating disturbances in mineral metabolism that have been associated with adverse clinical outcomes.