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Calcimimetics

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https://www.readbyqxmd.com/read/28803497/exploring-the-potential-value-of-improved-care-for-secondary-hyperparathyroidism-with-a-novel-calcimimetic-therapy
#1
Björn Stollenwerk, Sergio Iannazzo, Kerry Cooper, Vasily Belozeroff
AIMS: This study explored the use of a value-based pricing approach for the new calcimimetic etelcalcetide indicated for the treatment of secondary hyperparathyroidism (SHPT) in patients receiving hemodialysis. It used the US payer perspective and applied the cost-effectiveness framework. Because etelcalcetide is an intravenous therapy that can be titrated for individual patients, and because its utilization is yet to be assessed in real world settings, a range of plausible doses were estimated for etelcalcetide to define a range of prices...
August 14, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28794306/the-pharmacological-profile-and-the-clinical-efficacy-of-the-world-s-1st-intravenous-calcimimetics-etelcalcetide-hydrochloride-parsabiv-%C3%A2
#2
Kazutsune Harada, Atsuto Inoue, Akinori Yamauchi, Akifumi Fujii
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/28750928/paricalcitol-and-cinacalcet-have-disparate-actions-on-parathyroid-oxyphil-cell-content-in-patients-with-chronic-kidney-disease
#3
Cynthia Ritter, Brent Miller, Daniel W Coyne, Diptesh Gupta, Sijie Zheng, Alex J Brown, Eduardo Slatopolsky
The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28728941/comparison-of-calcimimetic-r568-and-calcitriol-in-mineral-homeostasis-in-the-hyp-mouse-a-murine-homolog-of-x-linked-hypophosphatemia
#4
Maren Leifheit-Nestler, Julia Kucka, Emi Yoshizawa, Geert Behets, Patrick D'Haese, Christian Bergen, Martin Meier, Dagmar-Christiane Fischer, Dieter Haffner
X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)2D3 (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health...
July 18, 2017: Bone
https://www.readbyqxmd.com/read/28673686/correction-of-25-oh-vitamin-d-deficiency-improves-control-of-secondary-hyperparathyroidism-and-reduces-the-inflammation-in-stable-haemodialysis-patients
#5
Raquel Ojeda López, Elvira Esquivias de Motta, Andrés Carmona, Victoria García Montemayor, Isabel Berdud, Alejandro Martín Malo, Pedro Aljama García
INTRODUCTION: Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. OBJECTIVE: To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency (<20ng/ml) on the control of secondary hyperparathyroidism and microinflammation status...
June 30, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28671062/a-12-week-dose-escalating-study-of-etelcalcetide-ono-5163-amg-416-%C3%A2-a-novel-intravenous-calcimimetic-for-secondary-hyperparathyroidism-in-%C3%A2-japanese-hemodialysis-patients%C3%A2
#6
Keitaro Yokoyama, Masafumi Fukagawa, Takashi Shigematsu, Takashi Akiba, Akifumi Fujii, Motoi Odani, Tadao Akizawa
AIMS: To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. MATERIALS AND METHODS: In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa)...
July 3, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28630081/calcium-sensing-receptor-genotype-and-response-to-cinacalcet-in-patients-undergoing-hemodialysis
#7
Sharon M Moe, Leah Wetherill, Brian Scott Decker, Dongbing Lai, Safa Abdalla, Jin Long, Matteo Vatta, Tatiana M Foroud, Glenn M Chertow
BACKGROUND AND OBJECTIVES: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in the calcium-sensing receptor (CASR) alter the response to the calcimimetic cinacalcet. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed DNA samples in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial, a randomized trial comparing cinacalcet to placebo on a background of usual care. Of the 3883 patients randomized, 1919 (49%) consented to DNA collection, and samples from 1852 participants were genotyped for 18 CASR polymorphisms...
July 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28615947/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-etelcalcetide
#8
REVIEW
Mario Cozzolino, Andrea Galassi, Ferruccio Conte, Michela Mangano, Luca Di Lullo, Antonio Bellasi
Secondary hyperparathyroidism (SHPT), a very frequent, severe, and worsening complication of chronic kidney disease, is characterized by high serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism. Clinically, SHPT shows renal osteodystrophy, vascular calcification, cardiovascular damage, and fatal outcome. Calcium-sensing receptor (CaSR) is the main physiological regulator of PTH secretion; its activation by calcium rapidly inhibits PTH. Another important player in regulating mineral metabolism is vitamin D receptor (VDR), which is under the influence of vitamin D and influences the intestinal absorption of calcium and phosphate, PTH gene expression, and bone calcium mobilization...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28597792/implications-of-the-calcium-sensing-receptor-in-ischemia-reperfusion
#9
François Paquot, Justine Huart, Jean-Olivier Defraigne, Jean-Marie Krzesinski, François Jouret
The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) which was first isolated from bovine parathyroid glands. Its complex structure has been well characterized, which helped to better understand its function. The CaSR activity can be modulated by various ligands, either activators (also called "calcimimetics") or inhibitors (or "calcilytics"). The main role of the CaSR concerns Ca(2+) homeostasis. In bone, intestine and kidney, the CaSR acts as a sensor for extracellular ionized Ca(2+) concentration ([Ca(2+)]e) to keep it stable...
April 2017: Acta Cardiologica
https://www.readbyqxmd.com/read/28538380/acute-effects-of-cinacalcet-on-arterial-stiffness-and-ventricular-function-in-hemodialysis-patients-a-randomized-double-blinded-crossover-study
#10
Aurélie Poulin, Pierre-Luc Bellemare, Catherine Fortier, Fabrice Mac-Way, Simon Desmeules, Karine Marquis, Valérie Gaudreault, Marcel Lebel, Mohsen Agharazii
BACKGROUND: Serum calcium concentration (Ca) plays an essential role in a vascular muscle tone and myocardial contractility. Previously, we showed that acutely lowering Ca by hemodialysis reduced arterial stiffness. Cinacalcet is a calcimimetic that lowers Ca and parathyroid hormone (PTH). The aim of the present study was to examine whether acute lowering of Ca by cinacalcet improves vascular stiffness and myocardial diastolic dysfunction. METHOD: This is a double-blinded randomized placebo-controlled crossover study that included 21 adult patients with end-stage kidney disease undergoing chronic hemodialysis...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28518414/systematic-review-of-surgical-and-medical-treatment-for-tertiary-hyperparathyroidism
#11
REVIEW
R R Dulfer, G J H Franssen, D A Hesselink, E J Hoorn, C H J van Eijck, T M van Ginhoven
BACKGROUND: A significant proportion of patients with chronic kidney disease and secondary hyperparathyroidism (HPT) remain hyperparathyroid after kidney transplantation, a state known as tertiary HPT. Without treatment, tertiary HPT can lead to diminished kidney allograft and patient survival. Parathyroidectomy was commonly performed to treat tertiary HPT until the introduction of the calcimimetic drug, cinacalcet. It is not known whether surgery or medical treatment is superior for tertiary HPT...
June 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28508965/cinacalcet-in-hyperparathyroidism-management-after-pediatric-renal-transplantation
#12
Olivier Niel, Anne Maisin, Marie-Alice Macher, Michel Peuchmaur, Georges Deschênes
Secondary hyperparathyroidism is often associated with end stage renal disease; even after renal transplantation, hyperparathyroidism may persist, and is responsible for hypercalcemia, hypophosphatemia and elevated parathyroid hormone (iPTH) levels. Parathyroid hyperplasia is frequently associated with persistent hyperparathyroidism, and may require a surgical treatment. Here, we report hyperparathyroidism along with parathyroid hyperplasia in a 7-year-old child, which persisted after renal transplant. Calcitonin and pamidronate failed to decrease serum calcium levels; clodronate was also inefficient...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28508378/population-pharmacokinetic-and-pharmacodynamic-modeling-of-etelcalcetide-in-patients-with-chronic-kidney-disease-and-secondary-hyperparathyroidism-receiving-hemodialysis
#13
Ping Chen, Adimoolam Narayanan, Benjamin Wu, Per Olsson Gisleskog, John P Gibbs, Andrew T Chow, Murad Melhem
INTRODUCTION: Etelcalcetide is a novel calcimimetic that binds and activates calcium-sensing receptors (CaSRs) for the treatment of secondary hyperparathyroidism (SHPT). METHODS: To assess titrated dosing regimens, population pharmacokinetic (PK) and PK/pharmacodynamic (PKPD) modeling of etelcalcetide was performed using NONMEM 7.2. In this analysis, plasma etelcalcetide, serum parathyroid hormone (PTH) and calcium (Ca) concentration-time data were collected from five phase I, II, and III clinical trials following single or multiple intravenous doses of etelcalcetide ranging from 2...
May 15, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28499709/mortality-in-dialysis-patients-with-cinacalcet-use-a-large-observational-registry-study
#14
Claudia Friedl, Gilbert Reibnegger, Reinhard Kramar, Emanuel Zitt, Stefan Pilz, Johannes F E Mann, Alexander R Rosenkranz
BACKGROUND: Secondary hyperparathyroidism (sHPT) is associated with higher mortality in dialysis patients. The calcimimetic cinacalcet reduces intact parathyroid hormone (iPTH) in dialysis patients. The randomized controlled EVOLVE trial failed to unequivocally prove survival advantage of cinacalcet in dialysis patients. However, recent post hoc analyses suggested a benefit in subgroups of dialysis patients. Large observational cohort studies may represent an option to better determine such subgroups...
July 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28473803/contemporary-medical-management-of-primary-hyperparathyroidism-a-systematic-review
#15
REVIEW
Julius Simoni Leere, Jesper Karmisholt, Maciej Robaczyk, Peter Vestergaard
INTRODUCTION: Primary hyperparathyroidism is increasingly an asymptomatic disease at diagnosis, but the recognized guidelines for management are based on evidence obtained from studies on patients with symptomatic disease, and surgery is not always indicated. Other patients are unable to undergo surgery, and thus a medical treatment is warranted. This systematic review provides an overview of the existing literature on contemporary pharmaceutical options available for the medical management of primary hyperparathyroidism...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28440773/impact-of-calcimimetics-in-surgery-of-secondary-hyperparathyroidism
#16
José Ruiz, Antonio Ríos, José Manuel Rodríguez, Santiago Llorente, Antonio Miguel Hernández, Pascual Parrilla
No abstract text is available yet for this article.
January 2017: Endocrinología, diabetes y nutrición
https://www.readbyqxmd.com/read/28431775/cinacalcet-hydrochloride
#17
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
#18
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
#19
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
#20
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
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