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Calcimimetics

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https://www.readbyqxmd.com/read/29348484/activation-of-ca2-sensing-receptor-as-a-protective-pathway-to-reduce-cadmium-induced-cytotoxicity-in-renal-proximal-tubular-cells
#1
Jie Gu, Shuya Dai, Yanmin Liu, Haitao Liu, Yao Zhang, Xingqi Ji, Feng Yu, Yang Zhou, Liang Chen, William Ka Fai Tse, Chris Kong Chu Wong, Binghai Chen, Haifeng Shi
Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29335796/association-between-frailty-and-bone-loss-in-patients-undergoing-maintenance-hemodialysis
#2
Kei Yoneki, Jun Kitagawa, Keika Hoshi, Manae Harada, Takaaki Watanabe, Takahiro Shimoda, Ryota Matsuzawa, Atsushi Yoshida, Yusuke Matsunaga, Yasuo Takeuchi, Kentaro Kamiya, Atsuhiko Matsunaga
Frailty is significantly associated with bone loss in the general population. However, it is unclear whether this association also exists in patients undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to assess the association between frailty and bone loss in patients undergoing hemodialysis. This cross-sectional study included 214 (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis three times per week, with a mean age of 67...
January 15, 2018: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/29247746/calcimimetic-r568-inhibits-tetrodotoxin-sensitive-colonic-electrolyte-secretion-and-reduces-c-fos-expression-in-myenteric-neurons
#3
Xiangrong Sun, Lieqi Tang, Steven Winesett, Wenhan Chang, Sam Xianjun Cheng
AIMS: Calcium-sensing receptor (CaSR) is expressed on neurons of both submucosal and myenteric plexuses of the enteric nervous system (ENS) and the CaSR agonist R568 inhibited Cl- secretion in intestine. The purpose of this study was to localize the primary site of action of R568 in the ENS and to explore how CaSR regulates secretion through the ENS. MATERIALS AND METHODS: Two preparations of rat proximal and distal colon were used. The full-thickness preparation contained both the submucosal and myenteric plexuses, whereas for the "stripped" preparation the myenteric plexus with the muscle layers was removed...
December 13, 2017: Life Sciences
https://www.readbyqxmd.com/read/29238762/etelcalcetide-injectable-calcimimetic-for-the-treatment-of-secondary-hyperparathyroidism-in-hemodialysis-dependent-patients
#4
P A Ureña Torres, J Bover, M Cohen-Solal
Chronic kidney disease is associated with mineral and bone disorders that are now considered as a syndrome. One of the major complications of this syndrome is secondary hyperparathyroidism (SHPT). SHPT increases bone turnover and the risk of fracture. SHPT is also associated with cardiovascular calcification and high mortality risk. The classical medical therapies of SHPT lack long-term efficacy and have undesirable effects on serum calcium and phosphate levels. Surgical parathyroidectomy is a radical therapeutic solution potentially exposing patients to a permanent state of hypoparathyroidism among other complications...
September 2017: Drugs of Today
https://www.readbyqxmd.com/read/29238578/bone-eating-kidney-disease
#5
Abhilash Koratala, Muhannad Leghrouz, Amir Kazory
In the current era of early detection of chronic kidney disease and efficient therapeutic options for management of its complications, skeletal manifestations of renal hyperparathyroidism are increasingly rare. A 31-year-old female patient presented for evaluation of severe pain in the left forearm, right hand, right knee, right hip, and lower back following a fall sustained 3 days prior to presentation. She had a history of end-stage renal disease and received maintenance hemodialysis. Review of the medical records revealed that she had poor compliance with her diet, medications, and dialysis treatments...
2017: SAGE Open Medical Case Reports
https://www.readbyqxmd.com/read/29196929/factors-associated-with-calcium-requirements-after-parathyroidectomy-in-chronic-kidney-disease-patients
#6
Yue Ding, Hongying Wang, Qiang Zou, Yiting Jin, Zijing Zhang, Junwen Huang
BACKGROUND: Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD). Parathyroidectomy (PTX) for these patients continues to be a valuable option in the era of calcimimetics. Postoperative hypocalcemia is common after surgery. The aim of this study was to identify clinical factors to define postoperative calcium requirements. METHODS: From February 2013 to May 2017, 68 patients with chronic kidney disease 5 (CKD5) who underwent PTX were reviewed...
December 1, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29192005/successful-reversal-of-furosemide-induced-secondary-hyperparathyroidism-with-cinacalcet
#7
Tarak Srivastava, Shahryar Jafri, William E Truog, Judith Sebestyen VanSickle, Winston M Manimtim, Uri S Alon
Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL...
December 2017: Pediatrics
https://www.readbyqxmd.com/read/29127708/calcimimetic-and-calcilytic-therapies-for-inherited-disorders-of-the-calcium-sensing-receptor-signalling-pathway
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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