Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism in stage 5 chronic kidney disease.
BACKGROUND
Chronic kidney disease (CKD) alters the regulation of calcium and phosphate homeostasis, leading to secondary hyperparathyroidism, metabolic bone disease, soft tissue calcifications, and other metabolic derangements that have a significant impact on morbidity and mortality. The parathyroid gland is the central organ responsible for regulating these adaptive responses. Suppression of parathyroid hormone (PTH) secretion, hypertrophy, and hyperplasia are a major goal of treatment of CKD.


METHODS
Current literature was reviewed and combined with the author's experience to address a number of issues regarding the optimal treatment of secondary hyperparathyroidism in hemodialysis patients.


RESULTS
The calcium sensing receptor (CASR) is the most important factor regulating parathyroid gland function, and allosteric modulators of CASR, called calcimimetics, provide a novel drug therapy to suppress PTH secretion. The current use of active vitamin D analogues to suppress PTH is often limited by hypercalcemia and hyperphosphatemia. Clinical trials of cinacalcet HCl, the first calcimimetic to be approved for treatment of secondary hyperparathyroidism in CKD, have demonstrated suppression of circulating PTH levels without increments in the calcium-phosphorus (Ca x P) product, making it easier to achieve the stringent management guidelines proposed for subjects with CKD by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI).


CONCLUSIONS
The management of disordered calcium and phosphate homeostasis in CKD patients is evolving based on our knowledge of the major importance of the calcium sensing receptor (CASR) in controlling parathyroid gland function and the potent actions of calcimimetics to target CASR. The purpose of this presentation is to provide an overview of the role of the CASR in regulation of parathyroid gland function, to examine the mechanisms whereby calcimimetics target the CASR, and to review the clinical trials that support the use of cinacalcet HCl for the treatment of secondary hyperparathyroidism in stage 5 chronic kidney disease (CKD).
Quarles
L Darryl
LD
Department of Internal Medicine, The Kidney Institute and Division of Nephrology, Kansas City, Kansas 66160, USA. dquarles@kumc.edu
D002908:Chronic Disease; D000069449:Cinacalcet; D002986:Clinical Trials as Topic; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology*; D007674:Kidney Diseases / Q000150:complications*; D009281:Naphthalenes / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D044169:Receptors, Calcium-Sensing / Q000187:drug effects
D009281:Naphthalenes; D044169:Receptors, Calcium-Sensing; D000069449:Cinacalcet