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https://www.readbyqxmd.com/read/29792272/facing-cinacalcet-induced-hypocalcemia-sit-back-and-relax
#1
Pieter Evenepoel, Rukshana Shroff
A post hoc analysis of data from the EVOLVE study demonstrates that cinacalcet-induced hypocalcemia is common, mostly asymptomatic, and resolves spontaneously. These findings are reassuring and may warrant therapeutic inertia. However, previous studies in parathyroidectomized patients suggest that calcium repletion may be beneficial and safe from bone and cardiovascular perspectives, respectively, and as such call into question the appropriateness of a "sit back and relax" attitude toward cinacalcet-induced hypocalcemia...
June 2018: Kidney International
https://www.readbyqxmd.com/read/29782837/phenylalanine-and-tryptophan-stimulate-gastrin-and-somatostatin-secretion-and-h-k-atpase-activity-in-pigs-through-calcium-sensing-receptor
#2
Yihan Xian, Xiuying Zhao, Chao Wang, Cuicui Kang, Liren Ding, Weiyun Zhu, Suqin Hang
In rodents and humans, aromatic amino acids increase gut hormone secretion and H+ -K+ -ATPase activity by modulating calcium-sensing receptor (CaSR). However, the role of CaSR and its related signaling molecules in amino acid-induced gut hormone secretion in swine has not been investigated. Here, we examined whether a CaSR-dependent pathway modulated gastrin and somatostatin (SS) secretion and H+ -K+ -ATPase activity in pigs. Perfusion of pig stomach tissues in the presence of extracellular 80 mM l-phenylalanine (Phe) or 20 mM l-tryptophan (Trp) and a CaSR agonist cinacalcet triggered gastrin and SS secretion and H+ -K+ -ATPase activity (P < 0...
May 18, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29764395/longitudinal-changes-in-bone-and-mineral-metabolism-after-cessation-of-cinacalcet-in-dialysis-patients-with-secondary-hyperparathyroidism
#3
Irene Ruderman, Edward R Smith, Nigel D Toussaint, Tim D Hewitson, Stephen G Holt
BACKGROUND: The calcimimetic agent cinacalcet is effective for the management of secondary hyperparathyroidism (SHPT) in dialysis patients. Changes to reimbursement of cinacalcet in Australia provided an opportunity to assess effects of medication cessation on biochemical and clinical outcomes in dialysis patients, including changes to novel biomarkers such as calciprotein particles (CPP). CPP are nanoparticles of mineral and protein in the circulation associated with increased vascular calcification in patients with chronic kidney disease...
May 15, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29763933/the-calcium-sensing-receptor-gene-polymorphism-rs1801725-and-calcium-related-phenotypes-in-hemodialysis-patients
#4
Alicja E Grzegorzewska, Dariusz Bednarski, Monika Świderska, Adrianna Mostowska, Paweł P Jagodziński
BACKGROUND/AIMS: The calcium-sensing receptor gene (CASR) rs1801725 variant is responsible for a non-conservative amino-acid change (A986S) in the calcium-sensing receptor cytoplasmic tail. We hypothesized that rs1801725 polymorphism might be helpful in understanding Ca-related abnormalities in HD patients. METHODS: In 1215 subjects (245 on cinacalcet), we determined the associations of rs1801725 with secondary hyperparathyroidism (sHPT)-related laboratory parameters, PTH-decreasing effect of cinacalcet hydrochloride, coronary artery disease (CAD), myocardial infarction (MI), nephrolithiasis-related ESRD, and mortality...
May 10, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29762046/effects-of-calcimimetics-on-long-term-outcomes-in-dialysis-patients-literature-review-and-bayesian-meta-analysis
#5
Greta Lozano-Ortega, Nathalie Waser, Mark E Bensink, Sarah Goring, Heather Bennett, Geoffrey A Block, Glenn M Chertow, Marie-Louise Trotman, Kerry Cooper, Adrian R Levy, Vasily Belozeroff
AIM: Randomized controlled trials (RCTs) with clinical outcomes are considered the gold standard for regulatory approval. However, by design they are only able to answer a small number of clinical questions. Other high-quality studies are required for clinical decision-making. The EVOLVE was the largest RCT, evaluating the effects of cinacalcet on clinical outcomes among adult patients receiving maintenance dialysis suffering from secondary hyperparathyroidism. While the EVOLVE trial did not reach its primary end point, imbalance in subjects' age at randomization and discontinuation rates are two of the reasons that the lack of mortality benefit is in question...
May 15, 2018: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/29753401/vitamin-d-and-calcimimetics-in-cardiovascular-disease
#6
REVIEW
Kenneth Lim, Takayuki Hamano, Ravi Thadhani
Cardiovascular disease has earned its place as one of the leading noncommunicable diseases that has become a modern-day global epidemic. The increasing incidence and prevalence of chronic kidney disease (CKD) has added to this enormous burden, given that CKD is now recognized as an established risk factor for accelerated cardiovascular disease. In fact, cardiovascular disease remains the leading cause of death in the CKD population, with significant prognostic implications. Alterations in vitamin D levels as renal function declines has been linked invariably to the development of cardiovascular disease beyond a mere epiphenomenon, and has become an important focus in recent years in our search for new therapies...
May 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29738034/evaluation-of-prevalence-biochemical-profile-and-drugs-associated-with-chronic-kidney-disease-mineral-and-bone-disorder-in-11-dialysis-centers
#7
Rodrigo Reis Abrita, Beatriz Dos Santos Pereira, Neimar da Silva Fernandes, Renata Abrita, Rosalia Maria Nunes Henriques Huaira, Marcus Gomes Bastos, Natália Maria da Silva Fernandes
INTRODUCTION: The diagnosis and treatment of mineral and bone disorder of chronic kidney disease (CKD-MBD) is a challenge for nephrologists and health managers. The aim of this study was to evaluate the prevalence, biochemical profile, and drugs associated with CKD-MBD. METHODS: Cross-sectional study between July and November 2013, with 1134 patients on dialysis. Sociodemographic, clinical, and laboratory data were compared between groups based on levels of intact parathyroid hormone (iPTH) (< 150, 150-300, 301-600, 601-1000, and > 1001 pg/mL)...
May 7, 2018: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29734949/a-case-of-hyperparathyroidism-associated-parkinsonism-successfully-treated-with-cinacalcet-hydrochloride-a-calcimimetic
#8
Yuichiro Ohya, Masato Osaki, Shota Sakai, Shunsuke Kimura, Chiharu Yasuda, Tetsuro Ago, Takanari Kitazono, Shuji Arakawa
BACKGROUND: Some metabolic disorders, including abnormal calcium metabolism, can develop and worsen parkinsonism. However, whether hyperparathyroidism can cause parkinsonism remains controversial. CASE PRESENTATION: An 83-year-old woman with a history of right thalamic hemorrhage and drug-induced parkinsonism, was admitted due to worsening of parkinsonian symptoms including mask-like face, bradykinesia, freezing of gait, and rigidity. She had been diagnosed with autoimmune hepatitis and was being treated with prednisolone...
May 7, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29724589/discovery-of-evocalcet-a-next-generation-calcium-sensing-receptor-agonist-for-the-treatment-of-hyperparathyroidism
#9
Hiroshi Miyazaki, Yousuke Ikeda, Osamu Sakurai, Tsutomu Miyake, Rie Tsubota, Jyunko Okabe, Masataka Kuroda, Yutaka Hisada, Tetsuya Yanagida, Hikaru Yoneda, Yukihito Tsukumo, Shin Tokunaga, Takehisa Kawata, Rikiya Ohashi, Hajime Fukuda, Koki Kojima, Ayako Kannami, Takayuki Kifuji, Naoya Sato, Akiko Idei, Taku Iguchi, Tetsuya Sakairi, Yasunori Moritani
The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism. Cinacalcet hydrochloride is a representative CaSR agonist which widely used for the hyperparathyroidism. However, it has several issues to clinical use, such as nausea/vomiting and strong inhibition of CYP2D6. We tried to improve these issues of cinacalcet for a new pharmaceutical agent as a preferable CaSR agonist...
April 24, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29714810/divergent-effects-of-strontium-and-calcium-sensing-receptor-positive-allosteric-modulators-calcimimetics-on-human-osteoclast-activity
#10
Natalie A Diepenhorst, Katie Leach, Andrew N Keller, Patricia Rueda, Anna E Cook, Tracie L Pierce, Cameron Nowell, Philippe Pastoureau, Massimo Sabatini, Roger J Summers, William N Charman, Patrick M Sexton, Arthur Christopoulos, Christopher J Langmead
BACKGROUND AND PURPOSE: Strontium ranelate, a drug approved, and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium-sensing receptor (CaSR). However, it is not known whether bone-targeted CaSR positive allosteric modulators (PAMs; calcimimetics) represent an alternative (or adjunctive) therapy to strontium (Sr2+ o ). EXPERIMENTAL APPROACH: We assessed three structurally distinct calcimimetics (cinacalcet, AC-265347 and a benzothiazole tri-substituted urea [BTU-compound 13]), alone and in combination with extracellular calcium (Ca2+ o ) or Sr2+ o , in G protein-dependent signalling assays and trafficking experiments in HEK293 cells and for their effects on cell differentiation, tartrate-resistant alkaline phosphatase (TRAP) activity and hydroxyapatite resorption assays in human blood-derived osteoclasts...
May 1, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29694950/is-sclerostin-level-associated-with-cardiovascular-diseases-in-hemodialysis-patients
#11
Gokce Kundakci Gelir, Sule Sengul, Gokhan Nergizoglu, Sehsuvar Ertürk, Neval Duman, Sim Kutlay
BACKGROUND/AIMS: The objective of this study is to evaluate the relation between sclerostin, arterial stiffness, and cardiovascular events (CVE) in hemodialysis patients (HD). METHODS: Sclerostin level and carotid-femoral pulse wave velocity (PWV) in 97 HD patients and sclerostin level in 40 controls were measured. RESULTS: Sclerostin level was significantly higher in patients than in controls. Sclerostin associated positively with age, male gender, cardiovascular disease, statin use, BMI, and PWV while negatively with alkaline phosphatase, parathormone (PTH), Kt/V, cinacalcet and vitamin D use in univariable correlation analyses...
April 25, 2018: Blood Purification
https://www.readbyqxmd.com/read/29691773/etelcalcetide-for-treating-secondary-hyperparathyroidism-an-evidence-review-group-evaluation-of-a-nice-single-technology-appraisal
#12
Micah Rose, Jonathan Shepherd, Petra Harris, Karen Pickett, Joanne Lord
The manufacturer of the calcimimetic drug etelcalcetide was invited to make an evidence submission as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) programme. Within this submission, they reported evidence on the clinical and cost effectiveness of etelcalcetide for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis. The Southampton Health Technology Assessments Centre (SHTAC), part of the Wessex Institute at the University of Southampton, was the independent Evidence Review Group (ERG) commissioned to appraise the company's submission...
April 25, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29691267/stability-of-extemporaneously-prepared-cinacalcet-oral-suspensions
#13
Kara Thomson, David J Hutchinson, Lipika Chablani
PURPOSE: The stability of extemporaneously prepared cinacalcet suspensions over 90 days was evaluated. METHODS: Cinacalcet 5-mg/mL suspension was prepared by triturating 30-mg cinacalcet tablets. Twelve 30-mL batches were prepared with a 1:1 mixture of Ora-Plus and either Ora-Sweet or Ora-Sweet SF (sugar free). Three suspensions of each kind were stored at both room temperature and refrigerated conditions. A 1-mL sample was taken from each bottle at 0, 7, 18, 32, 64, and 90 days...
May 1, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29680147/discovery-and-development-of-calcimimetic-and-calcilytic-compounds
#14
Edward F Nemeth, Bradford C Van Wagenen, Manuel F Balandrin
The extracellular calcium receptor (CaR) is a G protein-coupled receptor (GPCR) and the pivotal molecule regulating systemic Ca2+ homeostasis. The CaR was a challenging target for drug discovery because its physiological ligand is an inorganic ion (Ca2+ ) rather than a molecule so there was no structural template to guide medicinal chemistry. Nonetheless, small molecules targeting this receptor were discovered. Calcimimetics are agonists or positive allosteric modulators of the CaR, while calcilytics are antagonists and all to date are negative allosteric modulators...
2018: Progress in Medicinal Chemistry
https://www.readbyqxmd.com/read/29664140/performance-of-new-400-mhz-hts-power-driven-magnet-nmr-technology-on-typical-pharmaceutical-api-cinacalcet-hcl
#15
Maria Victoria Silva Elipe, Neil Donovan, Robert Krull, Donald Pooke, Kimberly L Colson
After years towards higher field strength magnets, NMR technology in commercial instruments in the past decade has expanded at low and high magnetic fields to take advantage of new opportunities. At lower field strengths, permanent magnets are well-established, whereas for mid-range and high field, developments utilize superconducting magnets cooled with cryogenic liquids. Recently, the desire to locate NMR spectrometers in non-typical NMR laboratories has created interest in the development of cryogen-free magnets...
April 17, 2018: Magnetic Resonance in Chemistry: MRC
https://www.readbyqxmd.com/read/29658374/hypercalcemic-crisis-in-third-trimenon-evaluating-the-optimal-treatment-strategy
#16
Julie Refardt, Patricia Farina, Irene Hoesli, Christian Meier
Hypercalcemia due to primary hyperparathyroidism during pregnancy is a rare condition and associated with increased morbidity and mortality for the mother and the unborn child. Whereas parathyroidectomy is favored during the second trimester, no clear recommendations exist for its management during the third trimenon. We here report the case of a 26-year-old woman in the 29th week of her first pregnancy, who was admitted to our clinic with hypertension, intra-uterine growth retardation and polyhydramnios. Severe hypercalcemia due to primary hyperparathyroidism was diagnosed (total calcium 3...
April 16, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29644071/clinical-management-of-patients-on-peritoneal-dialysis-in-italy-results-from-the-atena-study
#17
Carlo Crepaldi, Alessandro Possidoni, Flavia Caputo, Roberto Dell'Aquila, Emilio Giulio Galli, Anna Maria Costanzo, Giuliana Gualberti, Umberto di Luzio Paparatti, Roberto Russo
Background: In Italy, few studies have examined the clinical management of peritoneal dialysis (PD) patients, resulting in a lack of information and awareness. Methods: A total of 378 PD patients (64.7 ± 14.3 years, 58.9% males) were enrolled across 15 centres in a 12-month retrospective and 6-month prospective study. The primary objective was to evaluate the achievement of Kidney Disease Outcomes Quality Initiative and Kidney Disease Improving Global Outcomes guidelines on recommended target values for anaemia, high blood pressure and mineral metabolism...
April 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29614098/a-novel-calcimimetic-agent-evocalcet-mt-4580-khk7580-suppresses-the-parathyroid-cell-function-with-little-effect-on-the-gastrointestinal-tract-or-cyp-isozymes-in-vivo-and-in-vitro
#18
Takehisa Kawata, Shin Tokunaga, Miki Murai, Nami Masuda, Waka Haruyama, Youji Shoukei, Yutaka Hisada, Tetsuya Yanagida, Hiroshi Miyazaki, Michihito Wada, Tadao Akizawa, Masafumi Fukagawa
Cinacalcet hydrochloride (cinacalcet), an oral calcimimetic agent has been widely used for the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In sharp contrast to vitamin D receptor activators, cinacalcet suppresses SHPT without inducing hypercalcemia or hyperphosphatemia. Nevertheless, some patients remain refractory to SHPT with this agent, as the dose cannot be sufficiently increased due to gastrointestinal symptoms. In order to resolve this issue, we have developed a newly synthesized calcimimetic agent, evocalcet (MT-4580/KHK7580)...
2018: PloS One
https://www.readbyqxmd.com/read/29532306/calcimimetics-versus-parathyroidectomy-what-is-preferable
#19
REVIEW
M Rroji, G Spasovski
Secondary hyperparathyroidism (SHPT) is common among patients with end-stage renal disease (ESRD). SHPT is associated with high-turnover bone disease, interstitial and vascular calcifications, cardiovascular morbidity and mortality. The pharmacological management of SHPT has progressed in recent years. The introduction of targeted therapies, such as selective vitamin D receptors activators and calcium-sensing receptor modulators, offers an increased opportunity to adequately control elevated parathyroid hormone (PTH), especially in patients with chronic kidney disease under dialysis treatment...
March 12, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29525393/incidence-predictors-and-therapeutic-consequences-of-hypocalcemia-in-patients-treated-with-cinacalcet-in-the-evolve-trial
#20
Jürgen Floege, Kate Tsirtsonis, Jan Iles, Tilman B Drueke, Glenn M Chertow, Patrick Parfrey
The calcimimetic cinacalcet is used to treat secondary hyperparathyroidism in patients receiving dialysis, and asymptomatic hypocalcemia is often observed following its initiation. Here we investigated the incidence, predictors and therapeutic consequences of hypocalcemia by a post hoc analysis of the randomized, double-blind, placebo-controlled EValuation Of Cinacalcet Hydrochloride Therapy to Lower CardioVascular Events (EVOLVE) trial. Hypocalcemia was classified as mild (total serum calcium 8.0-8.39 mg/dL), moderate (7...
March 7, 2018: Kidney International
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