title: Cinacalcet upregulates calcium-sensing receptors of parathyroid glands in hemodialysis patients.
abstract: BACKGROUND
  Cinacalcet hydrochloride (cinacalcet), a calcimimetic, has been shown to upregulate calcium-sensing receptor (CaSR) expression in parathyroid glands of rats with chronic renal insufficiency. However, the effect of cinacalcet on the reduced CaSR expression in human parathyroid glands remains to be elucidated.
  
  
  METHODS
  Four normal parathyroid glands and 71 hyperplastic parathyroid glands from 18 hemodialysis patients with refractory secondary hyperparathyroidism (SHPT) treated with (n = 10; cinacalcet group) or without (n = 8; conventional group) cinacalcet were examined immunohistochemically with a specific antibody against CaSR. The expression level of CaSR was analyzed semiquantitatively.
  
  
  RESULTS
  Compared with normal glands, the immunohistochemical expression of CaSR was decreased significantly in both the cinacalcet and conventional groups. In the cinacalcet group, the expression of CaSR was increased significantly compared with that in the conventional group (1.83 ± 0.14 vs. 0.87 ± 0.15, p < 0.001), even though the proportion of patients using vitamin D sterols and the mean administered dose of calcitriol equivalents were not significantly different between the two groups. The expression of CaSR was significantly decreased in the larger glands (>500 mg) compared with that in the smaller glands (<500 mg) in both groups; furthermore, it was markedly decreased in areas of nodular hyperplasia compared with diffuse hyperplasia in the cinacalcet group.
  
  
  CONCLUSIONS
  Our results indicate that cinacalcet upregulates the depressed expression of CaSR in hemodialysis patients with SHPT, and that insufficient expression of CaSR, especially in larger glands with advanced nodular hyperplasia, underlies the pathogenesis of SHPT in patients who are resistant to cinacalcet.
authors.affiliation: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sumida
authors.forename: Michio
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ubara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Marui
authors.forename: Kiho
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kenmei
authors.initials: K
authors.lastname: Takaichi
authors.forename: Shinji
authors.initials: S
authors.lastname: Tomikawa
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoshita
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000069449:Cinacalcet; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use*; D010280:Parathyroid Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D006435:Renal Dialysis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D009281:Naphthalenes; D044169:Receptors, Calcium-Sensing; D000069449:Cinacalcet