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Fabio Vescini, Giorgio Borretta, Iacopo Chiodini, Marco Boniardi, Marina Carotti, Elena Castellano, Cristiana Cipriani, Cristina Eller-Vainicher, Sandro Giannini, Maurizio Iacobone, Antonio Stefano Salcuni, Federica Saponaro, Stefano Spiezia, Annibale Versari, Guido Zavatta, Zuzana Mitrova, Rosella Saulle, Simona Vecchi, Debora Antonini, Michele Basile, Alexia Giovanazzi, Agostino Paoletta, Enrico Papini, Agnese Persichetti, Irene Samperi, Alessandro Scoppola, Roberto Novizio, Pietro Giorgio Calò, Filomena Cetani, Luisella Cianferotti, Sabrina Corbetta, Maria Luisa De Rimini, Alberto Falchetti, Giovanni Iannetti, Stefano Laureti, Celestino Pio Lombardi, Bruno Madeo, Claudio Marcocci, Sandro Mazzaferro, Vittorio Miele, Salvatore Minisola, Andrea Palermo, Jessica Pepe, Alfredo Scillitani, Laura Tonzar, Franco Grimaldi, Renato Cozzi, Roberto Attanasio
AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices...
December 23, 2023: Endocrine, Metabolic & Immune Disorders Drug Targets
#2
REVIEW
Zhixing Song, Christopher Wu, Rongzhi Wang, Andrea Gillis, Jessica Fazendin, Brenessa Lindeman, Herbert Chen
BACKGROUND: The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy versus medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS: PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023...
April 5, 2024: Endocrine Practice
#3
JOURNAL ARTICLE
Hannah E Clark, Lauren A Trepanier, Michael W Wood
Cinacalcet is an oral calcimimetic that has potential to non-invasively treat primary hyperparathyroidism in dogs (Canis lupis familiaris). There is minimal data assessing its efficacy in dogs. This study aimed to determine whether a single dose of cinacalcet decreases serum ionized calcium (iCa), total calcium (tCa), and parathyroid hormone (PTH) concentrations. Twelve dogs received a median dose of 0.49 mg/kg (range 0.30-0.69 mg/kg) cinacalcet per os. Venous blood samples were collected at time 0 (before cinacalcet administration), 3, 8, and 24 h following cinacalcet administration...
April 2, 2024: Journal of Veterinary Pharmacology and Therapeutics
#4
JOURNAL ARTICLE
Arezoo Daryadel, Catharina J Küng, Betül Haykir, Sibylle Sabrautzki, Martin Hrabě de Angelis, Nati Hernando, Isabel Rubio-Aliaga, Carsten A Wagner
The kidney controls systemic inorganic phosphate (Pi) levels by adapting reabsorption to Pi intake. Renal Pi reabsorption is mostly mediated by sodium-phosphate cotransporters NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) which are tightly controlled by various hormones including parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). PTH and FGF23 rise in response to Pi intake and decrease NaPi-IIa and NaPi-IIc brush border membrane abundance enhancing phosphaturia. Phosphaturia and transporter regulation occur even in the absence of PTH and FGF23 signalling...
March 28, 2024: American Journal of Physiology. Renal Physiology
#5
JOURNAL ARTICLE
Kentaro Nakai, Keiji Kono, Shunsuke Yamada, Masatomo Taniguchi, Takayuki Hamano, Masafumi Fukagawa
INTRODUCTION: Several calcimimetics, other than cinacalcet, are commercially available; however, their effects on calcium and phosphate levels have not yet been fully studied. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the impact of calcimimetics on the management of serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis. METHODS: A systematic literature search through October 2023 and a meta-analysis were conducted on the effects of upacicalcet, etelcalcetide, evocalcet, and cinacalcet on serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis; we searched PubMed, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and 21 studies comprising 6371 patients undergoing dialysis were included...
March 18, 2024: Therapeutic Apheresis and Dialysis
#6
JOURNAL ARTICLE
Chien-Ming Lin, Yi-Xuan Ding, Shih-Ming Huang, Ying-Chuan Chen, Hwei-Jen Lee, Chih-Chien Sung, Shih-Hua Lin
CONTEXT: Although a monoallelic mutation in the calcium-sensing receptor ( CASR ) gene causes familial hypocalciuric hypercalcemia (FHH), the functional characterization of the identified CASR mutation linked to the clinical response to calcimimetics therapy is still limited. OBJECTIVE: A 45-year-old male presenting with moderate hypercalcemia, hypocalciuria, and inappropriately high parathyroid hormone (PTH) had a good response to cinacalcet (total serum calcium (Ca2+ ) from 12...
2024: Frontiers in Endocrinology
#7
Sneha Mohan, Michael Sheehan, Peter Tebben, Robert Wermers
Elevated 1,25-dihydroxyvitamin D (1,25(OH)2 D) is a rare cause of non-parathyroid hormone (PTH)-mediated hypercalcemia seen in granulomatous disease, malignancy (most often lymphoma), or genetic mutations. Therapeutic options are limited. We report the case of a 67-year-old White man with nonmalignant, nongranulomatous, 1,25(OH)2 D-mediated hypercalcemia treated successfully with cinacalcet. At presentation, he had hypercalcemia, hypercalciuria with recurrent nephrolithiasis, low PTH, elevated 1,25(OH)2 D, and normal 25-hydroxyvitamin D...
March 2024: JCEM Case Rep
#8
JOURNAL ARTICLE
A R Elfimova, A K Eremkina, O Yu Rebrova, E V Kovaleva, N G Mokrysheva
BACKGROUND: Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,» resulting in severe and persistent postoperative hypocalcemia...
February 28, 2024: Problemy E̊ndokrinologii
#9
JOURNAL ARTICLE
Zu-Ye Fang, Zi-Yuan Zhang, Yun-Dan Zheng, Dan Lei, Jianpeng Zhuang, Nan Li, Qing-Yu He, Xuesong Sun
BACKGROUND: MDR Staphylococcus aureus infections, along with the severity of biofilm-associated infections, continue to threaten human health to a great extent. It necessitates the urgent development of novel antimicrobial and antibiofilm agents. OBJECTIVES: To reveal the mechanism and target of cinacalcet as an antibacterial and antimicrobial agent for S. aureus. METHODS: Screening of non-antibiotic drugs for antibacterial and antibiofilm properties was conducted using a small-molecule drug library...
February 27, 2024: Journal of Antimicrobial Chemotherapy
#10
JOURNAL ARTICLE
Feng He, Cheng-Guo Wu, Yang Gao, Sabrina N Rahman, Magda Zaoralová, Makaía M Papasergi-Scott, Ting-Jia Gu, Michael J Robertson, Alpay B Seven, Lingjun Li, Jesper M Mathiesen, Georgios Skiniotis
The calcium-sensing receptor (CaSR) is a family C G-protein-coupled receptor1 (GPCR) that has a central role in regulating systemic calcium homeostasis2,3 . Here we use cryo-electron microscopy and functional assays to investigate the activation of human CaSR embedded in lipid nanodiscs and its coupling to functional Gi versus Gq proteins in the presence and absence of the calcimimetic drug cinacalcet. High-resolution structures show that both Gi and Gq drive additional conformational changes in the activated CaSR dimer to stabilize a more extensive asymmetric interface of the seven-transmembrane domain (7TM) that involves key protein-lipid interactions...
February 7, 2024: Nature
#11
JOURNAL ARTICLE
Lei He, Yuzhe Li, Jingjing Jin, Meijuan Cheng, Yaling Bai, Jinsheng Xu
BACKGROUND: Up to now, there is no unequivocal intervention to mitigate vascular calcification (VC) in patients with hemodialysis. This network meta-analysis aimed to systematically evaluate the clinical efficacy of sodium thiosulfate, bisphosphonates, and cinacalcet in treating vascular calcification. METHODS: A comprehensive study search was performed using PubMed, Web of Science, the Cochrane Library, EMBASE and China National Knowledge Internet (CNKI) to collect randomized controlled trials (RCTs) of sodium thiosulfate, bisphosphonates, and cinacalcet for vascular calcification among hemodialysis patients...
January 22, 2024: BMC Nephrology
#12
Fangyu Liu, Cheng-Guo Wu, Chia-Ling Tu, Isabella Glenn, Justin Meyerowitz, Anat Levit Kaplan, Jiankun Lyu, Zhiqiang Cheng, Olga O Tarkhanova, Yurii S Moroz, John J Irwin, Wenhan Chang, Brian K Shoichet, Georgios Skiniotis
Drugs acting as positive allosteric modulators (PAMs) to enhance the activation of the calcium sensing receptor (CaSR) and to suppress parathyroid hormone (PTH) secretion can treat hyperparathyroidism but suffer from side effects including hypocalcemia and arrhythmias. Seeking new CaSR modulators, we docked libraries of 2.7 million and 1.2 billion molecules against transforming pockets in the active-state receptor dimer structure. Consistent with the idea that docking improves with library size, billion-molecule docking found new PAMs with a hit rate that was 2...
December 27, 2023: bioRxiv
#13
JOURNAL ARTICLE
Mostafa Akbariani, Farahnaz Bidari Zerehpoosh, Zohreh Shahabi, Amir Shadboorestan, Zahra Hami, Ehsan Nasiroleslami, Sevda Shayesteh, Mohsen Chamanara, Ahmad Reza Dehpour
Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0...
January 6, 2024: Naunyn-Schmiedeberg's Archives of Pharmacology
#14
JOURNAL ARTICLE
Auryan Szalat, Shoshana Shpitzen, Rena Pollack, Haggi Mazeh, Ronen Durst, Vardiella Meiner
CONTEXT: A germline mutation can be identified in up to 10% of patients with primary hyperparathyroidism (PHPT). In 2017, a high frequency of the GCM2 [(NM_ 004752.4) c.1181A> C; p.Tyr394Ser; rs142287570] variant was reported in PHPT Ashkenazi Jews (AJ). OBJECTIVE: To evaluate the presence of the GCM2 p.Tyr394Ser variant in Israeli patients addressed for genetic evaluation to characterize their phenotype and clinical management. METHOD: Patients with PHPT who underwent addressed for genetic screening for suspected familial hypocalciuric hypercalcemia (FHH), a family history of isolated hyperparathyroidism (FIHP), or failed parathyroidectomy with persistent PHPT were recruited...
2023: Frontiers in Endocrinology
#15
JOURNAL ARTICLE
Udoamaka Ezuruike, Liam Curry, Oliver Hatley, Iain Gardner
AIM: To demonstrate the use of PBPK modelling to explore the impact of ethnic differences on drug PK. METHOD: A PBPK model developed for lansoprazole was used to predict the clinical PK of lansoprazole in Japanese subjects by incorporating the physiological parameters of a Japanese population into the model. Further verification of the developed Japanese population with clinical studies involving eight other CYP substrates- omeprazole, ticlopidine, alprazolam, midazolam, nifedipine, cinacalcet, paroxetine and dextromethorphan was also carried out...
December 10, 2023: British Journal of Clinical Pharmacology
#16
JOURNAL ARTICLE
Behram A Khan, XiaoJie Qu, Yan Hua, Muhammad M Javaid
Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD). The treatment for SHPT includes synthetic vitamin D analogs, calcitriol or calcimimetics...
November 2023: Curēus
#17
JOURNAL ARTICLE
Angela Yee-Moon Wang, Tak-Ka Tang, Yat-Yin Yau, Wai Kei Lo
RATIONALE & OBJECTIVE: Parathyroidectomy and calcimimetics have been used to reduce fracture risk in patients with kidney failure and advanced secondary hyperparathyroidism (SHPT), but direct comparisons of these treatment approaches have not been implemented. This pilot study compared their effects on bone mineral density (BMD) in this patient population. STUDY DESIGN: A prospective pilot open-label randomized trial. SETTING & PARTICIPANTS: 65 patients receiving maintenance peritoneal dialysis with advanced SHPT recruited from 2 university-affiliated hospitals in Hong Kong...
November 30, 2023: American Journal of Kidney Diseases
#18
JOURNAL ARTICLE
Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism.
Luiz Guilherme Fernandes Ramos, Daniela Del Pilar Via Reque Cortes, Luciene Machado Dos Reis, Fabio Luiz de Menezes Montenegro, Sérgio Samir Arap, Marília D'Elboux Guimarães Brescia, Melani Ribeiro Custódio, Vanda Jorgetti, Rosilene Motta Elias, Rosa Maria Affonso Moysés
INTRODUCTION: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. METHODS: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx)...
December 1, 2023: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
#19
JOURNAL ARTICLE
Zhaohui Ni, Xinling Liang, Chia-Chao Wu, Kyubok Jin, Yong-Lim Kim, Kuo-Cheng Lu, Tak Mao Chan, Masafumi Fukagawa, Jun Kinoshita, Chisato Nagai, Masahiro Kojima, Xueqing Yu
INTRODUCTION: Evocalcet is an oral calcimimetic agent with proven efficacy and safety in treating secondary hyperparathyroidism (SHPT) in Japanese patients on dialysis. METHODS: This randomized, double-blind, intrapatient dose-adjustment, parallel-group, international multicenter study compared the efficacy and safety of evocalcet versus cinacalcet for 52 weeks in East Asian hemodialysis patients with SHPT. RESULTS: In total, 203 and 200 patients were randomized to receive evocalcet or cinacalcet, respectively (overall, 70...
November 2023: KI Reports
#20
JOURNAL ARTICLE
Rongzhi Wang, Rhiannon D Reed, Griffin Price, Peter Abraham, Marshall Lewis, Jessica Liu McMullin, Paul MacLennan, Cozette Killian, Jayme E Locke, Song Ong, Vineeta Kumar, Andrea Gillis, Brenessa Lindeman, Herbert Chen, Jessica Fazendin
BACKGROUND: Hyperparathyroidism (HPT) and malignancy are the most common causes of hypercalcemia. Among kidney transplant (KT) recipients, hypercalcemia is mostly caused by tertiary HPT. Persistent tertiary HPT after KT is associated with allograft failure. Previous studies on managing tHPT were subjected to survivor treatment selection bias; as such, the impact of tertiary HPT treatment on allograft function remained unclear. We aim to assess the association between hypercalcemic tertiary HPT treatment and kidney allograft survival...
November 24, 2023: Oncologist
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