The role of calcimimetics in chronic kidney disease

Abstract

Secondary hyperparathyroidism (SHPT) develops in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. Treatment strategies directed to reduce the parathyroid hormone (PTH) concentrations have included phosphate binders and active vitamin D compounds. The over zealous use of these agents may result in hypercalcemia or overt calcium overload. Severe SHPT, hyperphosphatemia, and total body calcium overload have been implicated in the pathophysiology of skeletal and extraskeletal calcification and associated with increased morbidity and mortality among the dialysis population. Cinacalcet, the recently approved agent to lower PTH, activates the calcium-sensing receptor of the parathyroid gland amplifying the glands' sensitivity to extracellular ionized calcium concentration resulting in suppression of PTH secretion. Several clinical studies conducted in dialysis patients, have shown that cinacalcet in doses from 30 to 180 mg/day, significantly reduce PTH concentrations while simultaneously lowering calcium and phosphate levels. Respective to the National Kidney Foundation-Kidney Disease Outcomes and Quality Initiative (NKF-K/DOQI) recommended targets for bone and mineral metabolism, 41% of cinacalcet-treated patients achieved both PTH and calcium-phosphorus targets. The ability of cinacalcet to reduce PTH secretion, along with reductions in the serum calcium, phosphorus, and calcium-phosphorus product provide an alternative to the traditional treatment paradigm, and should be a welcomed addition to our therapeutic strategy in the management of SHPT. © 2006 International Society of Nephrology.