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https://www.readbyqxmd.com/read/28630081/calcium-sensing-receptor-genotype-and-response-to-cinacalcet-in-patients-undergoing-hemodialysis
#1
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...
June 19, 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
May 9, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28473803/contemporary-medical-management-of-primary-hyperparathyroidism-a-systematic-review
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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