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https://www.readbyqxmd.com/read/29786181/-new-scenarios-in-secondary-hyperparathyroidism-etelcalcetide-position-paper-of-nephrologists-form-lombardy
#1
Antonio Bellasi, Mario Cozzolino, Fabio Malberti, Giovanni Cancarini, Ciro Esposito, Augusto Genderini, Carlo Maria Guastoni, Patrizia Ondei, Giuseppe Pontoriero, Ugo Teatini, Giuseppe Vezzoli, Piergiorgio Messa, Francesco Locatelli
Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities...
May 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/29777154/calcimimetic-acts-on-enteric-neuronal-casr-to-reverse-cholera-toxin-induced-intestinal-electrolyte-secretion
#2
Lieqi Tang, Lingli Jiang, Megan E McIntyre, Ekaterina Petrova, Sam X Cheng
Treatment of acute secretory diarrheal illnesses remains a global challenge. Enterotoxins produce secretion through direct epithelial action and indirectly by activating enteric nervous system (ENS). Using a microperfused colonic crypt technique, we have previously shown that R568, a calcimimetic that activates the calcium-sensing receptor (CaSR), can act on intestinal epithelium and reverse cholera toxin-induced fluid secretion. In the present study, using the Ussing chamber technique in conjunction with a tissue-specific knockout approach, we show that the effects of cholera toxin and CaSR agonists on electrolyte secretion by the intestine can also be attributed to opposing actions of the toxin and CaSR on the activity of the ENS...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29767854/emerging-association-between-parathyroid-hormone-and-anemia-in-hemodialysis-patients
#3
REVIEW
Motoko Tanaka, Hirotaka Komaba, Masafumi Fukagawa
Anemia is a common complication of chronic kidney disease (CKD). There are various causes of renal anemia such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells, and bone marrow fibrosis. Secondary hyperparathyroidism (SHPT) is a less recognized, but potentially significant cause of renal anemia in CKD patients. Parathyroid hormone (PTH) has been regarded as a uremic toxin that has multiple adverse effects, and its elevated levels have been associated with renal anemia in hemodialysis patients...
May 16, 2018: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29764395/longitudinal-changes-in-bone-and-mineral-metabolism-after-cessation-of-cinacalcet-in-dialysis-patients-with-secondary-hyperparathyroidism
#4
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/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/29734949/a-case-of-hyperparathyroidism-associated-parkinsonism-successfully-treated-with-cinacalcet-hydrochloride-a-calcimimetic
#7
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/29733462/current-and-potential-therapeutic-strategies-for-the-management-of-vascular-calcification-in-patients-with-chronic-kidney-disease-including-those-on-dialysis
#8
REVIEW
Irene Ruderman, Stephen G Holt, Tim D Hewitson, Edward R Smith, Nigel D Toussaint
Patients with CKD have accelerated vascular stiffening contributing significantly to excess cardiovascular morbidity and mortality. Much of the arterial stiffening is thought to involve vascular calcification (VC), but the pathogenesis of this phenomenon is complex, resulting from a disruption of the balance between promoters and inhibitors of calcification in a uremic milieu, along with derangements in calcium and phosphate metabolic pathways. Management of traditional cardiovascular risk factors to reduce VC may be influential but has not been shown to significantly improve mortality...
May 7, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29719376/theoretical-overview-of-clinical-and-pharmacological-aspects-of-the-use-of-etelcalcetide-in-diabetic-patients-undergoing-hemodialysis
#9
REVIEW
Jianzhen Ye, Guangrui Deng, Feng Gao
Etelcalcetide is the first intravenous calcimimetic agent authorized for the treatment of secondary hyperparathyroidism (sHPT) in patients undergoing hemodialysis in Europe, the US, and Japan. The relationship between sHPT and diabetes resides on complex, bidirectional effects and largely unknown homeostatic mechanisms. Although 30% or more patients with end-stage renal disease are diabetics and about the same percentage of those patients suffer from sHPT associated with hemodialysis, no data on the specificities of the use of etelcalcetide in such patients are available yet...
2018: Drug Design, Development and Therapy
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/29691773/etelcalcetide-for-treating-secondary-hyperparathyroidism-an-evidence-review-group-evaluation-of-a-nice-single-technology-appraisal
#11
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/29680147/discovery-and-development-of-calcimimetic-and-calcilytic-compounds
#12
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/29677006/evidence-basis-for-integrated-management-of-mineral-metabolism-in-patients-with-end-stage-renal-disease
#13
Julia J Scialla
PURPOSE OF REVIEW: Treatment of mineral metabolism is a mainstay of dialysis care including some of its most widely used and costly pharmaceuticals. Although many mineral metabolites are associated with increased risk of mortality, cardiovascular disease, and other morbidities, few clinical trials are available to guide therapy and most focus on single drug approaches. In practice, providers manage many aspects of mineral metabolism simultaneously in integrated treatment approaches that incorporate multiple agents and changes in the dialysis prescription...
April 6, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29617283/regulation-of-bicarbonate-secretion-in-marine-fish-intestine-by-the-calcium-sensing-receptor
#14
Sílvia F Gregório, Juan Fuentes
In marine fish, high epithelial intestinal HCO₃− secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR) in the regulation of HCO₃− secretion in the intestine of the sea bream ( Sparus aurata L.). Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine...
April 4, 2018: International Journal of Molecular Sciences
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
#15
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/29606543/a-phase-i-open-label-single-dose-micro-tracer-mass-balance-study-of-14-c-labeled-asp7991-in-healthy-japanese-male-subjects-using-accelerator-mass-spectrometry
#16
Daisuke Miyatake, Naoyuki Nakada, Akitsugu Takada, Kota Kato, Yuta Taniuchi, Masataka Katashima, Taiji Sawamoto
ASP7991 is a calcimimetic that acts on the calcium-sensing receptor on parathyroid cell membranes and suppresses parathyroid hormone (PTH) secretion in the treatment of secondary hyperparathyroidism. The mass balance and metabolite profile of [14 C]ASP7991 were investigated in six healthy male subjects after a single oral dose of [14 C]ASP7991 [1 mg, 18.5 kBq (500 nCi)] in solution. [14 C] radioactivity in plasma, urine and feces was analyzed using Accelerator mass spectrometry. ASP7991 was rapidly absorbed, metabolized and excreted...
March 7, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29552709/use-of-calcimimetics-in-children-with-normal-kidney-function
#17
Judith Sebestyen VanSickle, Tarak Srivastava, Uri S Alon
The calcium-sensing receptor (CaSR) plays an important role in the homeostasis of serum ionized calcium by regulating parathyroid hormone (PTH) secretion and tubular calcium handling. Calcimimetics, which act by allosteric modulation of the CaSR, mimic hypercalcemia resulting in suppression of PTH release and increase in calciuria. Mostly used in children to treat secondary hyperparathyroidism associated with advanced renal failure, we have shown that calcimimetics can also be successfully used in children with bone and mineral disorders in which elevated PTH plays a detrimental role in skeletal pathophysiology in the face of normal kidney function...
March 19, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29545131/-utilization-of-alfacalcidol-and-active-vitamin-d-analogs-in-chronic-kidney-disease
#18
Pablo Antonio Ureña-Torres, Mario Cozzolino, Jordi Bover
Secondary hyperparathyroidism (SHPT) is one of the most frequent and deleterious complication of chronic kidney disease (CKD). SHPT is also one of the principal components of the now called CKD-mineral and bone disorders (MBD) syndrome. It is usually prevented and treated by vitamin D derivatives. However, the rationale for the prescription of vitamin D sterols in those patients is still a matter of hotly debates, mainly because of unsatisfactory results from numerous observational and not well-controlled studies...
March 12, 2018: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29534286/clinical-pharmacokinetics-and-pharmacodynamics-of-etelcalcetide-a-novel-calcimimetic-for-treatment-of-secondary-hyperparathyroidism-in-patients-with-chronic-kidney-disease-on-hemodialysis
#19
REVIEW
Benjamin Wu, Murad Melhem, Raju Subramanian, Ping Chen, Bethlyn Jaramilla Sloey, Bruno Fouqueray, M Benjamin Hock, Gary L Skiles, Andrew T Chow, Edward Lee
Etelcalcetide, a d-amino acid peptide, is an intravenous calcimimetic approved for the treatment of secondary hyperparathyroidism. Etelcalcetide binds the calcium-sensing receptor and increases its sensitivity to extracellular calcium, thereby decreasing secretion of parathyroid hormone (PTH) by chief cells. Etelcalcetide and its low-molecular-weight transformation products are rapidly cleared by renal excretion in healthy subjects, but clearance is substantially reduced and dependent on hemodialysis in end-stage renal disease...
March 13, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29532306/calcimimetics-versus-parathyroidectomy-what-is-preferable
#20
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
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