Evocalcet prevents ectopic calcification and parathyroid hyperplasia in rats with secondary hyperparathyroidism
Open Access
- 28 April 2020
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 15 (4), e0232428
- https://doi.org/10.1371/journal.pone.0232428
Abstract
Background Elevated parathyroid hormone (PTH) levels in secondary hyperparathyroidism (SHPT) lead to vascular calcification, which is associated with cardiovascular events and mortality. Increased PTH production is caused by the excessive proliferation of parathyroid gland cells, which is accelerated by abnormal mineral homeostasis. Evocalcet, an oral calcimimetic agent, inhibits the secretion of PTH from parathyroid gland cells and has been used for the management of SHPT in dialysis patients. We observed the effects of evocalcet on ectopic calcification and parathyroid hyperplasia using chronic kidney disease (CKD) rats with SHPT. Methods CKD rats with SHPT induced by adenine received evocalcet orally for 5 weeks. The calcium and inorganic phosphorus content in the aorta, heart and kidney was measured. Ectopic calcified tissues were also assessed histologically. To observe the effects on the proliferation of parathyroid gland cells, parathyroid glands were histologically assessed in CKD rats with SHPT induced by 5/6 nephrectomy (Nx) after receiving evocalcet orally for 4 weeks. Results Evocalcet prevented the increase in calcium and inorganic phosphorus content in the ectopic tissues and suppressed calcification of the aorta, heart and kidney in CKD rats with SHPT by reducing the serum PTH and calcium levels. Evocalcet suppressed the parathyroid gland cell proliferation and reduced the sizes of parathyroid cells in CKD rats with SHPT. Conclusions These findings suggest that evocalcet would prevent ectopic calcification and suppress parathyroid hyperplasia in patients with SHPT.This publication has 42 references indexed in Scilit:
- Cinacalcet in Patients with Chronic Kidney Disease: A Cumulative Meta-Analysis of Randomized Controlled TrialsPLoS Medicine, 2013
- Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKDNephrology Dialysis Transplantation, 2011
- Decreases in PTH in Japanese Hemodialysis Patients with Secondary HyperparathyroidismClinical Journal of the American Society of Nephrology, 2011
- Cinacalcet Effectively Reduces Parathyroid Hormone Secretion and Gland Volume Regardless of Pretreatment Gland Size in Patients with Secondary HyperparathyroidismClinical Journal of the American Society of Nephrology, 2010
- Decreases in Parathyroid Gland Volume after Cinacalcet Treatment in Hemodialysis Patients with Secondary HyperparathyroidismNephron Clinical Practice, 2010
- Does Vitamin D Receptor and Calcium Receptor Activation Therapy Play a Role in the Histopathologic Alterations of Parathyroid Glands in Refractory Uremic Hyperparathyroidism?Clinical Journal of the American Society of Nephrology, 2008
- Effect of Cinacalcet Hydrochloride, a New Calcimimetic Agent, on the Pharmacokinetics of Dextromethorphan: In Vitro and Clinical StudiesThe Journal of Clinical Pharmacology, 2007
- Pharmacokinetics of Cinacalcet Hydrochloride When Administered with KetoconazoleClinical Pharmacokinetics, 2007
- Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidismKidney International, 2005
- Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA proteinNature, 1997