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Calcimimetics

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https://www.readbyqxmd.com/read/29127708/calcimimetic-and-calcilytic-therapies-for-inherited-disorders-of-the-calcium-sensing-receptor-signalling-pathway
#1
REVIEW
Fadil M Hannan, Mie K Olesen, Rajesh V Thakker
THE CALCIUM-SENSING RECEPTOR (CAS RECEPTOR) PLAYS A PIVOTAL ROLE IN EXTRACELLULAR CALCIUM HOMEOSTASIS AND GERMLINE LOSS- AND GAIN-OF-FUNCTION MUTATIONS CAUSE FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH) AND AUTOSOMAL DOMINANT HYPOCALCAEMIA (ADH), RESPECTIVELY. CAS RECEPTOR SIGNAL TRANSDUCTION IN THE PARATHYROID GLANDS IS LIKELY REGULATED BY G-PROTEIN SUBUNIT Α11 (GΑ11) AND ADAPTOR-RELATED PROTEIN COMPLEX-2 SIGMA SUBUNIT (AP2Σ), AND RECENT STUDIES HAVE IDENTIFIED GERMLINE MUTATIONS OF THESE PROTEINS AS A CAUSE OF FHH AND/OR ADH...
November 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29108515/long-term-use-of-cinacalcet-in-kidney-transplant-recipients-with-hypercalcemic-secondary-hyperparathyroidism-a-single-center-prospective-study
#2
Vasileios Zavvos, Lamprini Fyssa, Marios Papasotiriou, Evangelos Papachristou, Theodoros Ntrinias, Eirini Savvidaki, Dimitrios S Goumenos
OBJECTIVES: Persistent secondary hyperparathyroidism is common after successful kidney transplant, with concomitant hypercalcemia and hypophosphatemia potentially leading to reduced graft survival and increased cardiovascular risk. Cinacalcet, a calcimimetic agent that activates the calcium-sensing receptors in parathyroid glands, is a therapeutic option. In this study, we assessed the long-term treatment effects of cinacalcet for a period of up to 5 years in a cohort of kidney transplant recipients...
October 31, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29078759/endothelin-a-receptor-blocker-and-calcimimetic-in-the-adenine-rat-model-of-chronic-renal-insufficiency
#3
Suvi Törmänen, Ilkka Pörsti, Päivi Lakkisto, Ilkka Tikkanen, Onni Niemelä, Timo Paavonen, Jukka Mustonen, Arttu Eräranta
BACKGROUND: We studied whether endothelin receptor antagonist and calcimimetic treatments influence renal damage and kidney renin-angiotensin (RA) components in adenine-induced chronic renal insufficiency (CRI). METHODS: Male Wistar rats (n = 80) were divided into 5 groups for 12 weeks: control (n = 12), 0.3% adenine (Ade; n = 20), Ade + 50 mg/kg/day sitaxentan (n = 16), Ade + 20 mg/kg/day cinacalcet (n = 16), and Ade + sitaxentan + cinacalcet (n = 16)...
October 27, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29067991/does-combination-of-paricalcitol-with-cinacalcet-in-secondary-hyperparathyroidism-in-hemodialysis-treatment-make-sense
#4
Jacek Zawierucha, Jolanta Małyszko, Jacek Małyszko, Tomasz Prystacki, Wojciech Marcinkowski, Teresa Dryl-Rydzyńska
INTRODUCTION    Secondary hyperparathyroidism (SHPT) is a common hormonal disorder associated with  chronic kidney disease (CKD). SHPT treatment should lead to reduction of parathormon concentration by calcimimetics or active vitamin D administration and calcium-phosphate metabolism stabilization. In the event of failure of conservative treatment complete or partial parathyroid resection should be considered.  OBJECTIVES    The aim of the study was assessement of beneficial effects of treatment with paricalcitol and cinacalcet simultaneously versus paricalcitol alone...
October 25, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29046478/cinacalcet-corrects-hypercalcemia-in-mice-with-an-inactivating-g%C3%AE-11-mutation
#5
Sarah A Howles, Fadil M Hannan, Caroline M Gorvin, Sian E Piret, Anju Paudyal, Michelle Stewart, Tertius A Hough, M Andrew Nesbit, Sara Wells, Stephen Dm Brown, Roger D Cox, Rajesh V Thakker
Loss-of-function mutations of GNA11, which encodes G-protein subunit α11 (Gα11), a signaling partner for the calcium-sensing receptor (CaSR), result in familial hypocalciuric hypercalcemia type 2 (FHH2). FHH2 is characterized by hypercalcemia, inappropriately normal or raised parathyroid hormone (PTH) concentrations, and normal or low urinary calcium excretion. A mouse model for FHH2 that would facilitate investigations of the in vivo role of Gα11 and the evaluation of calcimimetic drugs, which are CaSR allosteric activators, is not available...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29038882/etelcalcetide-a-novel-calcimimetic-prevents-vascular-calcification-in-a-rat-model-of-renal-insufficiency-with-secondary-hyperparathyroidism
#6
Longchuan Yu, James E Tomlinson, Shawn T Alexander, Kelly Hensley, Chun-Ya Han, Denise Dwyer, Marina Stolina, Charles Dean, William G Goodman, William G Richards, Xiaodong Li
Etelcalcetide, a novel peptide agonist of the calcium-sensing receptor, prevents vascular calcification in a rat model of renal insufficiency with secondary hyperparathyroidism. Vascular calcification occurs frequently in patients with chronic kidney disease (CKD) and is a consequence of impaired mineral homeostasis and secondary hyperparathyroidism (SHPT). Etelcalcetide substantially lowers parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) levels in SHPT patients on hemodialysis. This study compared the effects of etelcalcetide and paricalcitol on vascular calcification in rats with adenine-induced CKD and SHPT...
December 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28992983/primary-hyperparathyroidism
#7
REVIEW
Manuel Muñoz-Torres, Antonia García-Martín
Primary hyperparathyroidism (PHPT) is a common endocrinological process, characterized by chronic elevation of serum concentrations of calcium and parathyroid hormone (PTH). Many years ago, the most frequent forms of clinical presentation were symptomatic renal or skeletal disease with moderate or severe hypercalcemia; however, currently, most patients have few symptoms and mild hypercalcemia. A new form of presentation called normocalcemic PHPT has also been described but clinical consequences are not well established...
October 6, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28980761/parathyroid-nodular-hyperplasia-and-responsiveness-to-drug-therapy-in-renal-secondary-hyperparathyroidism-an-open-question
#8
REVIEW
Carlo Vulpio, Maurizio Bossola
The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of calcium and vitamin D, to arrest or reverse the parathyroid hyperplasia. However, when nodular hyperplasia or an autonomous adenoma develops, surgery may be indicated. We reviewed the literature with the aim of defining if the echographic criteria predictive of unresponsiveness of SHPT to calcitriol therapy are valid also in the cinacalcet era and if drug therapy may reverse nodular hyperplasia of parathyroid gland (PTG)...
October 5, 2017: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/28945857/calcimimetic-use-in-familial-hypocalciuric-hypercalcemia-a-perspective-in-endocrinology
#9
Stephen J Marx
Context: Familial hypocalciuric hypercalcemia (FHH) causes lifelong hypercalcemia that even persists after subtotal parathyroidectomy. Symptoms are usually mild. Past recommendations have often been for monitoring and against surgical or pharmacologic treatments. Methods: Review of publications about FHH, calcium-sensing receptors (CaSRs), and calcimimetics. Results: FHH reflects heterozygous germline mutation of CASR, GNA11, or AP2S1. These mutations inactivate the CaSRs in the parathyroid cell...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28939921/pathophysiology-and-treatment-of-cardiovascular-disease-in-pediatric-chronic-kidney-disease
#10
REVIEW
Nadine Khouzam, Katherine Wesseling-Perry
Life expectancy in patients with all stages of chronic kidney disease (CKD) falls far short of that in the general population. Cardiovascular disease is the leading cause of mortality in pediatric patients with CKD. In contrast to the intimal atherosclerotic lesions that characterize cardiovascular disease in the general population, vascular endothelial dysfunction, medial arterial calcification, and cardiac dysfunction contribute to cardiovascular pathological conditions in CKD. The pathogenesis of these lesions, the origins of which can be identified in the absence of traditional cardiovascular risk factors, is incompletely understood...
September 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28869940/severe-secondary-hyperparathyroidism-in-a-hemodialysis-patient-a-case-report-from-mongolia
#11
Saruultuvshin Adiya, Khurtsbayar Damdinsuren, Chuluuntsetseg Dorj
Secondary hyperparathyroidism (SHPT) occurs in patients with chronic renal failure complicated with renal bone disease and soft tissue/vascular calcification. In dialysis patients with severe SHPT, medical treatment may fail and parathyroidectomy (PTX) is indicated for definitive treatment. Severe hypocalcemia from hungry bone disease or postoperative hypoparathyroidism may occur during the postoperative period. We report here a case of severe SHPT in a hemodialysis patient treated with phosphate binders, calcitriol, and calcimimetics but who still required PTX...
2017: Blood Purification
https://www.readbyqxmd.com/read/28843775/parathyroid-hormone-contributes-to-the-down-regulation-of-cytochrome-p450-3a-through-the-camp-pi3k-pkc-pka-nf-%C3%AE%C2%BAb-signaling-pathway-in-secondary-hyperparathyroidism
#12
Hiroshi Watanabe, Ryusei Sugimoto, Komei Ikegami, Yuki Enoki, Tadashi Imafuku, Rui Fujimura, Jing Bi, Kento Nishida, Yoshiaki Sakaguchi, Michiya Murata, Hitoshi Maeda, Kenshiro Hirata, Sachiko Jingami, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Chronic kidney disease (CKD), which affects, not only renal clearance, but also non-renal clearance, is accompanied by a decline in renal function. Although it has been suggested that humoral factors, such as uremic toxins that accumulate in the body under CKD conditions, could be involved in the changes associated with non-renal drug clearance, the overall process is not completely understood. In this study, we report on the role of parathyroid hormone (PTH), a middle molecule uremic toxin, on the expression of drug metabolizing or transporting proteins using rats with secondary hyperparathyroidism (SHPT) as models...
August 24, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28836058/long-term-effects-of-etelcalcetide-as-intravenous-calcimimetic-therapy-in-hemodialysis-patients-with-secondary-hyperparathyroidism
#13
Takashi Shigematsu, Masafumi Fukagawa, Keitaro Yokoyama, Takashi Akiba, Akifumi Fujii, Motoi Odani, Tadao Akizawa
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a serious major complication in hemodialysis patients with chronic kidney disease. Long-term maintenance of serum phosphate, calcium, and parathyroid hormone (PTH) levels in appropriate ranges in these patients is a major challenge. We investigated the efficacy and safety of long-term treatment with etelcalcetide, a novel intravenous calcimimetic, in Japanese SHPT patients on long-term hemodialysis. METHODS: This study was a multicenter open-label study...
August 23, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28831705/predictors-of-first-ischemic-lower-limb-ulcer-in-dialysis-patients-an-observational-cohort-study
#14
Simeone Andrulli, Chiara Chiavenna, Maria Carla Bigi, Monica Crepaldi, Cesare Dell'Oro, Flavia Tentori, Celestina Manzoni, Giuseppe Bacchini, Mauro Maria Corti, Giuseppe Pontoriero
BACKGROUND: Lower limb ischemia affects the quality of life, physical activity and life expectancy of dialysis patients. The aim of this study was to investigate the risk factors associated with ischemic foot ulcers considering clinical, laboratory and therapeutic domains. METHODS: This observational cohort study was based on data from the Nephrology and Dialysis Department database of Alessandro Manzoni Hospital, Lecco (Italy). All of the incident patients who started dialysis between 1 January 1999 and 29 February 2012 were enrolled, excluding temporary guests, patients with acute renal failure and patients with previous limb ischemia or amputation...
August 22, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28803497/exploring-the-potential-value-of-improved-care-for-secondary-hyperparathyroidism-with-a-novel-calcimimetic-therapy
#15
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
#16
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%C3%A2-on-parathyroid-oxyphil-cell-content-in%C3%A2-patients-with-chronic-kidney-disease
#17
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...
November 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
#18
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
#19
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
#20
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
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