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Published on: August 28, 2018
Cinacalcet: will it play a role in reducing cardiovascular events?
1Division of Cardiology & Department of Medicine, Emory University, 1365 Clifton Rd NE, AT-504, Atlanta, GA 30322, USA.
Insights
Secondary hyperparathyroidism in chronic kidney disease causes bone and cardiovascular issues. Cinacalcet, a calcimimetic, targets the calcium-sensing receptor to manage these complications, improving patient outcomes.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD), linked to significant morbidity and mortality.
- SHPT involves elevated parathyroid hormone (PTH) levels, increased bone turnover, and adverse cardiovascular effects like calcification and cardiomyopathy.
- Current management of SHPT in CKD patients presents ongoing challenges.
Purpose of the Study:
- To review the role of cinacalcet, a calcimimetic agent, in managing SHPT.
- To explore cinacalcet's potential in preventing and mitigating cardiovascular calcification and uremic cardiomyopathy in CKD.
- To examine the calcium-sensing receptor (CaSR) as a therapeutic target in CKD-related cardiovascular disease.
Main Methods:
- Review of existing literature on secondary hyperparathyroidism, chronic kidney disease, and calcimimetics.
- Analysis of cinacalcet's mechanism of action as a calcimimetic and its effect on the CaSR.
- Examination of studies investigating cardiovascular outcomes in CKD patients treated with cinacalcet.
Main Results:
- Cinacalcet effectively reduces parathyroid hormone levels by activating the CaSR, thereby inhibiting PTH secretion.
- Evidence suggests cinacalcet may play a role in preventing or slowing cardiovascular calcification in CKD patients.
- The CaSR's presence in cardiovascular tissues indicates its potential involvement in CKD-related cardiovascular pathophysiology.
Conclusions:
- Cinacalcet is an effective oral therapy for SHPT in CKD, offering benefits beyond PTH reduction.
- Targeting the CaSR with cinacalcet presents a promising therapeutic strategy for cardiovascular complications in CKD.
- Further research is warranted to fully elucidate cinacalcet's cardiovascular protective effects in the CKD population.
Abstract:
Secondary hyperparathyroidism is a common complication of chronic kidney disease and it is associated with high morbidity and mortality. It is characterized by high parathyroid hormone levels and bone turnover leading to bone pain, deformity and fragility. Furthermore, secondary hyperparathyroidism adversely affects the cardiovascular system and has been associated with cardiovascular calcification and cardiomyopathy. Cinacalcet, a type II calcimimetic, is an effective and well-tolerated oral therapy for the management of secondary hyperparathyroidism. It is an allosteric activator of the calcium-sensing receptor enhancing sensitivity of parathyroid cells to extracellular calcium, which leads to inhibition of parathyroid hormone secretion. The calcium-sensing receptor expression in cardiomyocytes, endothelial cells and vascular smooth muscle cells raises the possibility that this receptor may be implicated in the pathophysiology of cardiovascular disease and constitute a potential therapeutic target. This article reviews the role of the calcimimetic agent cinacalcet in the prevention and progression of cardiovascular calcification and uremic cardiomyopathy in the chronic kidney disease setting.
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