Read by QxMD icon Read


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
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
Shane D Hellyer, Sabine Albold, Taide Wang, Amy Ny Chen, Lauren T May, Katie Leach, Karen J Gregory
Numerous positive and negative allosteric modulators (PAMs and NAMs) of Class C G protein-coupled receptors (GPCRs) have been developed as valuable preclinical pharmacological tools and therapeutic agents. While many Class C GPCR allosteric modulators have undergone subtype selectivity screening, most assay paradigms have failed to perform rigorous pharmacological assessment. Utilizing mGlu5 as a representative Class C GPCR, we tested the hypothesis that allosteric modulator selectivity was based on cooperativity rather than affinity...
March 7, 2018: Molecular Pharmacology
Primploy Greeviroj, Thidarat Kitrungphaiboon, Pisut Katavetin, Kearkiat Praditpornsilpa, Somchai Eiam-Ong, Bertrand L Jaber, Paweena Susantitaphong
BACKGROUND: Cinacalcet could decrease serum calcium, phosphate, and parathyroid hormone (PTH) in previous meta-analyses. However, the effect of cinacalcet on the new biomarkers such as fibroblast growth factor-23 (FGF-23), bone markers, and vascular calcification are still unestablished. We conducted a meta-analysis to examine the effects of cinacalcet on all laboratory and clinical spectrums of chronic kidney disease-mineral bone disorders (CKD-MBD). METHODS: A systematic literature search was conducted in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and Clinical Trials...
March 7, 2018: Nephron
A Yajima, K Tsuchiya, L F Bonewald, M Inaba, Y Tominaga, T Tanizawa, A Ito, K Nitta
Evaluation of bone is of great importance in chronic kidney disease patients, as these patients are at an increased risk for fractures. We treated a hemodialysis patient suffering from hyperparathyroid bone disease with cinacalcet hydrochloride and concurrent administration of maxacalcitol and alfacalcidol for a year. Hyperparathyroid bone disease is characterized by cortical thinning, increased cortical porosity, reduced trabecular bone volume, and increased hypomineralized matrix volume, and there is little information to date about the effects of treatment with cinacalcet hydrochloride on the bone fragility in patients with hyperparathyroid bone disease...
February 28, 2018: Osteoporosis International
Guoqi Wang, Hongyan Liu, Chengzhi Wang, Xiaojian Ji, Weijun Gu, Yiming Mu
To assess the efficacy and safety of cinacalcet on secondary hyperparathyroidism in patients with chronic kidney disease, Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched until March 2016. Trial sequential analysis (TSA) was conducted to control the risks of type I and II errors and calculate required information size (RIS). A total of 25 articles with 8481 participants were included. Compared with controls, cinacalcet administration did not reduce all-cause mortality (RR = 0...
February 15, 2018: Scientific Reports
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
Tibor Fülöp, Christian A Koch, Abdeen R Farah Musa, Christopher M Clark, Kamel A Gharaibeh, Zsolt Lengvársky, Mehrdad Hamrahian, Karen T Pitman, Mehul P Dixit
BACKGROUND: The long-term results of surgical parathyroidectomy (PTX) in end-stage renal disease (ESRD) patients are less well known in the modern era of newer activated vitamin-D analogs, calcimimetics and intraoperative monitoring of parathyroid hormone (PTH). METHODS: We performed a retrospective chart review of all ESRD patients undergoing PTX at the University of Mississippi Medical Center between January 2005 and August 2011, with follow-up data as available up to 4 years...
February 15, 2018: Hemodialysis International
Keith E Eidman, James B Wetmore
Secondary hyperparathyroidism (SHPT) is common in patients receiving maintenance hemodialysis and is associated with adverse outcomes. Currently, SHPT is managed by reducing circulating levels of phosphate with oral binders and parathyroid hormone (PTH) with vitamin D analogs and/or the calcimimetic cinacalcet. Etelcalcetide, a novel calcimimetic administered intravenously (IV) at the end of a hemodialysis treatment session, effectively reduces PTH in clinical trials when given thrice weekly. Additional clinical effects include reductions in circulating levels of phosphate and FGF-23 and an improved profile of markers of bone turnover...
2018: International Journal of Nephrology and Renovascular Disease
Cai-Mei Zheng, Chia-Chao Wu, Chi-Feng Hung, Min-Tser Liao, Jia-Fwu Shyu, Yung-Ho Hsu, Chien-Lin Lu, Yuan-Hung Wang, Jing-Quan Zheng, Tian-Jong Chang, Yuh-Feng Lin, Kuo-Cheng Lu
We evaluated the improvement of intact parathyroid hormone (iPTH) levels and bone parameters by supplementing nutritional vitamin D (cholecalciferol) to combined calcimimetic (cinacalcet) and active vitamin D analog (calcitriol) among severe secondary hyperparathyroidism (SHPT) hemodialysis (HD) patients. A randomized, controlled open-label study was undertaken in 60 HD patients with serum iPTH > 1000 pg/mL or persistently high iPTH ≥ 600 pg/mL even after >3 months of calcitriol (3 μg/week). The study group received oral cholecalciferol (5000 IU/ day) and the control group received a placebo...
February 10, 2018: Nutrients
Luciano Pereira, Catarina Meng, Daniela Marques, João M Frazão
Secondary hyperparathyroidism (SHPT) is associated with increased bone turnover, risk of fractures, vascular calcifications, and cardiovascular and all-cause mortality. The classical treatment for SHPT includes active vitamin D compounds and phosphate binders. However, achieving the optimal laboratory targets is often difficult because vitamin D sterols suppress parathyroid hormone (PTH) secretion, while also promoting calcium and phosphate intestinal absorption. Calcimimetics increase the sensitivity of the calcium-sensing receptor, so that even with lower levels of extracellular calcium a signal can still exist, leading to a decrease of the set-point for systemic calcium homeostasis...
February 2018: Clinical Kidney Journal
Björn Stollenwerk, Sergio Iannazzo, Ron Akehurst, Michael Adena, Andrew Briggs, Bastian Dehmel, Patrick Parfrey, Vasily Belozeroff
INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet...
February 2, 2018: PharmacoEconomics
Marie Evans, Shona Methven, Alessandro Gasparini, Peter Barany, Kate Birnie, Stephanie MacNeill, Margaret T May, Fergus J Caskey, Juan-Jesus Carrero
With the aim to expand the randomized controlled trial evidence of cinacalcet treatment to the unselected, general chronic kidney disease (CKD) population we analysed a large inception cohort of CKD patients in the region of Stockholm, Sweden 2006-2012 (both non-dialysis, dialysis and transplanted) with evidence of secondary hyperparathyroidism (SHPT). We used marginal structural models to account for both confounding by indication and time-dependent confounding. Over 37 months, 435/3,526 (12%) initiated cinacalcet de novo...
February 1, 2018: Scientific Reports
Luigi Cirillo, Pamela Gallo, Carmela Errichiello, Annasara Sorrentino, Alma Mehmetaj, Marco Gregori, Rossella Cannavò, Giuseppe Cestone, Roberta Cutruzzulà, Pietro Claudio Dattolo
Disorders of calcium-phosphate-parathormone balance, are very important issues in ESRD patients, that may lead to severe complications, as dystrophic calcinosis cutis, a rare disease, caused by calcium salt deposits in cutaneous or subcutaneous tissues and many organs. We present the case of a 47 years old woman, in ESRD due to membranous glomerulopathy, treated by peritoneal dialysis, who, after 7 months of dialysis, developed painful masses on second finger and fifth metacarpus of the right hand. Laboratory and instrumental data showed hyperparathyroidism with a parathyroid mass consistent with adenoma...
February 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Noman Ahmad, Mona Bahasan, Balgees Abdulhadi Abdullah Al-Ghamdi, Halah Faleh Al-Enizi, Ali Saeed Al-Zahrani
Neonatal severe hyperparathyroidism (NSHPT) is a rare autosomal recessive disease. Children present within the first 6 months of life and more commonly in the first few weeks. Common presentation is poor feeding, polyuria, dehydration, lethargy, failure to thrive, hypotonia, gastrointestinal dysmotility, osteopenia and symptoms of respiratory distress due to a poorly developed chest cage. We present a case of a 2-month old girl with severe hypercalcemia and hyperparathyroidism. She was found to have a novel homozygous mutation in the acceptor splicing site of intron 4 (c...
September 2017: Clinical Cases in Mineral and Bone Metabolism
Amanda D'Espessailles, Yuly A Mora, Cecilia Fuentes, Mariana Cifuentes
The study of the mechanisms that trigger inflammation in adipose tissue is key to understanding and preventing the cardiometabolic consequences of obesity. We have proposed a model where activation of the G protein-coupled calcium sensing receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon activation, CaSR can mediate the expression and secretion of proinflammatory factors in human preadipocytes, adipocytes and adipose tissue explants. One possible pathway involved in CaSR-induced inflammation is the activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes maturation and secretion of interleukin (IL)-1β...
January 18, 2018: Journal of Cellular Physiology
Caroline M Gorvin, Raghu Metpally, Victoria J Stokes, Fadil M Hannan, Sarath B Krishnamurthy, John D Overton, Jeffrey G Reid, Gerda E Breitwieser, Rajesh V Thakker
Mutations of the sigma subunit of the heterotetrameric adaptor-related protein complex 2 (AP2σ) impair signalling of the calcium-sensing receptor (CaSR), and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3-associated AP2σ mutations have only been identified at one residue, Arg15. We hypothesized that additional rare AP2σ variants may also be associated with altered CaSR function and hypercalcaemia, and sought for these by analysing >111,995 exomes (>60,706 from ExAc and dbSNP, and 51,289 from the Geisinger Health System-Regeneron DiscovEHR dataset which also contains clinical data)...
January 9, 2018: Human Molecular Genetics
Mengyuan Cao, Xu Xue, Xixi Pei, Yiwen Qian, Lan Liu, Lili Ren, Guoguang Chen
The present research indicated that a new self-microemulsifying drug delivery systems (SMEDDS) were used to reduce the food effect of poorly water-soluble drug cinacalcet and enhance the bioavailability in beagle dogs by oral gavage. Ethyl oleate, OP-10 and PEG-200 was selected as the oil phase, surfactant and co-surfactant of cinacalcet-SMEDDS by the solubility and phase diagram studies. Central Composite Design-Response Surface Methodology was used to determine the ratio of surfactant and co-surfactant, the amount of oil for optimizing the SMEDDS formation...
January 9, 2018: Drug Development and Industrial Pharmacy
Keiichi Otsuka, Yoichi Ohno, Joji Oshima
This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23 HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47...
November 2018: Renal Failure
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
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"