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Calcimimetics

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https://www.readbyqxmd.com/read/28431775/cinacalcet-hydrochloride
#1
Gamal A E Mostafa, Abdullah A Al-Badr
Cinacalcet hydrochloride is a calcimimetic agent that increases the sensitivity to the extracellular calcium of the calcium-sensing receptors of the parathyroid gland which regulates parathyroid hormone secretion. This comprehensive profile on cinacalcet hydrochloride starts with a description: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and applications of the drug are included. The methods of preparation of cinacalcet hydrochloride are described and their respective schemes are outlined...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28429550/parathyroid-hormone-targets-in-chronic-kidney-disease-and-managing-severe-hyperparathyroidism
#2
Carmel M Hawley, Stephen G Holt
Appropriate targets for parathyroid hormone (PTH) in patients with chronic kidney disease (CKD) stages 3-5D are controversial, as are the means by which these targets might be achieved. Secondary hyperparathyroidism is linked to symptoms like bone pain and itch, in addition to less clinically overt issues like bone fragility as well as vascular and soft tissue calcification which may lead to adverse hard endpoints, particularly fracture and death. Recognized therapies for managing a rising PTH include vitamin D analogues, with or without calcimimetic (where available), in addition to management of serum mineral concentrations with diet, binders and dialysis...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28390426/successful-treatment-of-early-allograft-dysfunction-with-cinacalcet-in-a-patient-with-nephrocalcinosis-caused-by-severe-hyperparathyroidism-a-case-report
#3
Boonyarit Cheunsuchon, Suchai Sritippayawan
BACKGROUND: Hyperparathyroidism is common in patients undergoing kidney transplantation. Occasionally, this condition can cause early allograft dysfunction by inducing calcium phosphate deposition in the allograft, which results in nephrocalcinosis. Although nephrocalcinosis occurs occasionally in kidney allografts, it has only rarely been reported in the literature. CASE PRESENTATION: Here, we present the case of a 58-year-old Thai woman with severe hyperparathyroidism who received a living-related kidney transplant from her 35-year-old son...
April 8, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28380670/improved-regeneration-and-de-novo-bone-formation-in-a-diabetic-zebrafish-model-treated-with-paricalcitol-and-cinacalcet
#4
Filipe R Carvalho, Ana R Fernandes, M Leonor Cancela, Paulo J Gavaia
Bone changes related to diabetes have been well stablished, but few strategies have been developed to prevent this growing health problem. In our work we propose to investigate the effects of calcitriol as well as of a vitamin D analog (paricalcitol) and a calcimimetic (cinacalcet), in fin regeneration and de novo mineralization in a zebrafish model of diabetes. Following exposure of diabetic transgenic Tg(ins:nfsb-mCherry) zebrafish to calcitriol, paricalcitol and cinacalcet, caudal fins were amputated to assess their effects on tissue regeneration...
April 5, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28346348/vitamin-d-in-chronic-kidney-disease-and-dialysis-patients
#5
REVIEW
Guillaume Jean, Jean Claude Souberbielle, Charles Chazot
Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue...
March 25, 2017: Nutrients
https://www.readbyqxmd.com/read/28336834/-parenteral-calcimimetics-for-the-treatment-of-secondary-hyperparathyroidism
#6
Naoto Hamano, Masafumi Fukagawa
The oral calcimimetics, cinacalcet, is reported to be effective on secondary hyperparathyroidism resistant to classical treatment like phosphate binders or vitamin D receptor activator. The problem that gastrointestinal adverse events cause poor adherence, drug discontinuation, and insufficient dose escalation remains unsolved. The novel injectable calcimimetic, etelcalcetide, is recently developed and is expected to reduce such adverse events and improve the therapeutic effects on moderate to severe secondary hyperparathyroidism...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336833/-oral-calcimimetics-on-secondary-hyperparathyroidism-of-uremia
#7
Yasuo Imanishi
Secondary hyperparathyroidism of uremia is associated with poor health outcomes, including all-cause mortality, cardiovascular mortality, and fractures. Standard therapy for secondary hyperparathyroidism includes vitamin D receptor activators, and phosphate binders. Persistently elevated parathyroid hormone(PTH)levels may require the addition of calcimimetics which sensitizes calcium-sensing receptors on the parathyroid glands.
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336832/-surgical-and-non-surgical-management-of-primary-hyperparathyroidism-how-do-calcimimetics-work
#8
Yasuhiro Takeuchi
Primary hyperparathyroidism is a common endocrine disease. The first line therapy for the disease is surgical removal of affected parathyroid gland(s). Other therapeutic options with medication are needed to be established, because many of patients with primary hyperparathyroidism have few or no symptoms and are expected to have a long life expectancy without surgery. Cinacalcet as a calcimimetic, bisphosphonates and denosumab are promising candidates for medical management of the disease. Effectiveness and efficiency of these drugs for patients with primary hyperparathyroidism is to be evaluated in comparison with surgical treatment...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336830/-the-discovery-research-and-development-of-etelcalcetide-hydrochloride-the-world-1st-intravenous-calcimimetics
#9
Atsuto Inoue, Kazutsune Harada
Etelcalcetide hydrochloride is the first intravenous calcimimetics agent for secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is to be administered through dialysis circuit by physician or medical staff upon completion of dialysis and such administration is expected to reduce the burden of medication in patients. From the nonclinical study results, etelcalcetide functions as an allosteric activator of calcium-sensing receptor(CaSR). Etelcalcetide suppressed PTH secretion both in vitro and in vivo...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336829/-the-effect-of-oral-calcimimetics-on-cardiovascular-events
#10
Takayuki Hamano
The Evolve Trial showed no significant benefit of cinacalcet on the primary composite outcome(death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event)but significantly reduced the incidence of heart failure in an intention-to-treat(ITT)analysis. In an adjusted ITT analysis and lag-censoring analysis, the effect of cinacalcet on the primary outcome was significant. The reduced incidence of cardiovascular events in the cinacalcet arm could by predicted by a >=30% reduction in FGF23 levels at week 20...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336828/-disorders-caused-by-mutations-in-calcium-sensing-receptor-and-related-diseases
#11
Toshimi Michigami
Sensing of extracellular calcium(Ca2+)levels involves the Ca-sensing receptor(CaSR), its downstream signaling molecule Gα11, and the adaptor-related protein complex 2(AP2)that plays a role in clathrin-dependent endocytosis of CaSR. Inactivating mutations in CaSR cause familial hypocalciuric hypercalcemia type 1(FHH1)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations lead to autosomal dominant hypocalcemia type 1(ADH1)and Bartter syndrome type Ⅴ. Recent studies have identified that inactivating mutations in Gα11 and σ-subunit of AP2(AP2σ)also cause FHH, and these conditions have been classified as FHH2 and FHH3, respectively...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28277829/etelcalcetide-for-the-treatment-of-secondary-hyperparathyroidism
#12
REVIEW
Naoto Hamano, Hirotaka Komaba, Masafumi Fukagawa
Calcium sensing receptor is an important target for the treatment of secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a novel peptide calcimimetic agent that has a similar mechanism of action as cinacalcet hydrochloride. Clinical trials of etelcalcetide have been performed in the US, Europe, and Japan, and these trials demonstrated the safety and efficacy of etelcalcetide in dialysis patients. Etelcalcetide has recently been approved in Europe, the US and Japan. Areas covered: We review the development, pharmacokinetics, and clinical efficacy and safety of etelcalcetide for the treatment of SHPT in hemodialysis patients...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28143438/medication-adherence-in-randomized-controlled-trials-evaluating-cardiovascular-or-mortality-outcomes-in-dialysis-patients-a-systematic-review
#13
Karumathil M Murali, Judy Mullan, Jenny H C Chen, Steven Roodenrys, Maureen Lonergan
BACKGROUND: Medication non-adherence is common among renal dialysis patients. High degrees of non-adherence in randomized controlled trials (RCTs) can lead to failure to detect a true treatment effect. Cardio-protective pharmacological interventions have shown no consistent benefit in RCTs involving dialysis patients. Whether non-adherence contributes to this lack of efficacy is unknown. We aimed to investigate how medication adherence and drug discontinuation were assessed, reported and addressed in RCTs, evaluating cardiovascular or mortality outcomes in dialysis patients...
January 31, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28134399/-nephrolithiasis-associated-with-normocalcemic-or-hypercalcemic-primary-hyperparathyroidism-focus-on-calciomimetics
#14
Simone Brardi, Roberto Ponchietti, Ennio Duranti
Primary hyperparathyroidism (PHPT) is a disease involving a broad range of alterations of calcium homeostasis, sustained by parathyroid hormone (PTH) levels that are clearly abnormal. The anomalies directly associated with hyperparathyroidism are nephrolithiasis and fibrocystic bone disease. Since PHPT resolves when abnormal parathyroid tissue is removed, surgery is clearly the only definitive approach to this type of hyperparathyroidism. However there are large subgroups of patients for whom medical therapy should be considered instead of surgery...
November 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28122587/diseases-associated-with-calcium-sensing-receptor
#15
REVIEW
C Vahe, K Benomar, S Espiard, L Coppin, A Jannin, M F Odou, M C Vantyghem
The calcium-sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone secretion and urinary calcium excretion. The diseases caused by an abnormality of the CaSR are genetically determined or are more rarely acquired. The genetic diseases consist of hyper- or hypocalcemia disorders. Hypercalcaemia disorders are related to inactivating mutations of the CASR gene either heterozygous (autosomal dominant familial benign hypercalcaemia, still named hypocalciuric hypercalcaemia syndrome type 1) or homozygous (severe neonatal hyperparathyroidism)...
January 25, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28097356/effect-of-etelcalcetide-vs-cinacalcet-on-serum-parathyroid-hormone-in-patients-receiving-hemodialysis-with-secondary-hyperparathyroidism-a-randomized-clinical-trial
#16
RANDOMIZED CONTROLLED TRIAL
Geoffrey A Block, David A Bushinsky, Sunfa Cheng, John Cunningham, Bastian Dehmel, Tilman B Drueke, Markus Ketteler, Reshma Kewalramani, Kevin J Martin, Sharon M Moe, Uptal D Patel, Justin Silver, Yan Sun, Hao Wang, Glenn M Chertow
Importance: Secondary hyperparathyroidism contributes to extraskeletal calcification and is associated with all-cause and cardiovascular mortality. Control is suboptimal in the majority of patients receiving hemodialysis. An intravenously (IV) administered calcimimetic could improve adherence and reduce adverse gastrointestinal effects. Objective: To evaluate the relative efficacy and safety of the IV calcimimetic etelcalcetide and the oral calcimimetic cinacalcet...
January 10, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28097355/effect-of-etelcalcetide-vs-placebo-on-serum-parathyroid-hormone-in-patients-receiving-hemodialysis-with-secondary-hyperparathyroidism-two-randomized-clinical-trials
#17
RANDOMIZED CONTROLLED TRIAL
Geoffrey A Block, David A Bushinsky, John Cunningham, Tilman B Drueke, Markus Ketteler, Reshma Kewalramani, Kevin J Martin, T Christian Mix, Sharon M Moe, Uptal D Patel, Justin Silver, David M Spiegel, Lulu Sterling, Liron Walsh, Glenn M Chertow
Importance: Secondary hyperparathyroidism contributes to extraskeletal complications in chronic kidney disease. Objective: To evaluate the effect of the intravenous calcimimetic etelcalcetide on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis. Design, Setting, and Participants: Two parallel, phase 3, randomized, placebo-controlled treatment trials were conducted in 1023 patients receiving hemodialysis with moderate to severe secondary hyperparathyroidism...
January 10, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28097342/second-chances-to-improve-esrd-outcomes-with-a-second-generation-calcimimetic
#18
EDITORIAL
John P Middleton, Myles Wolf
No abstract text is available yet for this article.
January 10, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28062938/mineral-metabolism-and-cardiovascular-disease-in-ckd
#19
REVIEW
Hideki Fujii, Nobuhiko Joki
The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease...
March 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28057872/a-phase-3-multicentre-randomized-double-blind-placebo-controlled-parallel-group-study-to-evaluate-the-efficacy-and-safety-of-etelcalcetide-ono-5163-amg-416-a-novel-intravenous-calcimimetic-for-secondary-hyperparathyroidism-in-japanese-haemodialysis-patients
#20
Masafumi Fukagawa, Keitaro Yokoyama, Takashi Shigematsu, Takashi Akiba, Akifumi Fujii, Takuto Kuramoto, Motoi Odani, Tadao Akizawa
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT. METHODS: In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2...
January 5, 2017: Nephrology, Dialysis, Transplantation
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