Etelcalcetide, A Novel Calcimimetic, Prevents Vascular Calcification in A Rat Model of Renal Insufficiency with Secondary Hyperparathyroidism
| Autor: | Chun-Ya Han, Xiaodong Li, William G. Richards, Shawn T. Alexander, James E. Tomlinson, Longchuan Yu, Charles W. Dean, Denise Dwyer, William G. Goodman, Marina Stolina, Kelly Hensley |
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| Rok vydání: | 2017 |
| Předmět: |
Paricalcitol
Male Fibroblast growth factor-23 (FGF23) medicine.medical_specialty Calcimimetic Endocrinology Diabetes and Metabolism 030232 urology & nephrology Parathyroid hormone 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine Animals Orthopedics and Sports Medicine Renal Insufficiency Rats Wistar Vascular Calcification Original Research Etelcalcetide business.industry Parathyroid chief cell medicine.disease Uremia Rats Disease Models Animal Secondary hyperparathyroidism Ergocalciferols Hyperparathyroidism Secondary business Peptides medicine.drug Kidney disease |
| Zdroj: | Calcified Tissue International |
| ISSN: | 1432-0827 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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