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Etelcalcetide, A Novel Calcimimetic, Prevents Vascular Calcification in A Rat Model of Renal Insufficiency with Secondary Hyperparathyroidism.

Authors
  • Yu, Longchuan1
  • Tomlinson, James E1
  • Alexander, Shawn T1
  • Hensley, Kelly1
  • Han, Chun-Ya1
  • Dwyer, Denise1
  • Stolina, Marina1
  • Dean, Charles Jr1
  • Goodman, William G1
  • Richards, William G1
  • Li, Xiaodong2
  • 1 Departments of Cardiometabolic Disorders and Comparative Biology and Safety Sciences, Amgen Inc., One Amgen Center Drive, MS: 36-2-A, Thousand Oaks, CA, 91320, USA.
  • 2 Departments of Cardiometabolic Disorders and Comparative Biology and Safety Sciences, Amgen Inc., One Amgen Center Drive, MS: 36-2-A, Thousand Oaks, CA, 91320, USA. [email protected]
Type
Published Article
Journal
Calcified Tissue International
Publisher
Springer-Verlag
Publication Date
Dec 01, 2017
Volume
101
Issue
6
Pages
641–653
Identifiers
DOI: 10.1007/s00223-017-0319-7
PMID: 29038882
Source
Medline
Keywords
License
Unknown

Abstract

Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperparathyroidism. Vascular calcification occurs frequently in patients with chronic kidney disease (CKD) and is a consequence of impaired mineral homeostasis and secondary hyperparathyroidism (SHPT). Etelcalcetide substantially lowers parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) levels in SHPT patients on hemodialysis. This study compared the effects of etelcalcetide and paricalcitol on vascular calcification in rats with adenine-induced CKD and SHPT. Uremia and SHPT were induced in male Wistar rats fed a diet supplemented with 0.75% adenine for 4 weeks. Rats were injected with vehicle, etelcalcetide, or paricalcitol for 4 weeks from the beginning of adenine diet. Rats fed an adenine-free diet were included as nonuremic controls. Similar reductions in plasma PTH and parathyroid chief cell proliferation were observed in both etelcalcetide- and paricalcitol-treated rats. Serum calcium and phosphorus were significantly lower in etelcalcetide-treated uremic rats and was unchanged in paricalcitol-treated rats. Both serum FGF23 and aortic calcium content were significantly lower in etelcalcetide-treated uremic rats compared with either vehicle- or paricalcitol-treated uremic rats. The degree of aortic calcium content for etelcalcetide-treated rats was similar to that in nonuremic controls and corroborated findings of lack of histologic aortic mineralization in those groups. In conclusion, etelcalcetide and paricalcitol similarly attenuated progression of SHPT in an adenine rat model of CKD. However, etelcalcetide differentially prevented vascular calcification, at least in part, due to reductions in serum FGF23, calcium, and phosphorus levels.

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