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https://www.readbyqxmd.com/read/28062938/mineral-metabolism-and-cardiovascular-disease-in-ckd
#1
REVIEW
Hideki Fujii, Nobuhiko Joki
The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease...
January 6, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28057872/a-phase-3-multicentre-randomized-double-blind-placebo-controlled-parallel-group-study-to-evaluate-the-efficacy-and-safety-of-etelcalcetide-ono-5163-amg-416-a-novel-intravenous-calcimimetic-for-secondary-hyperparathyroidism-in-japanese-haemodialysis-patients
#2
Masafumi Fukagawa, Keitaro Yokoyama, Takashi Shigematsu, Takashi Akiba, Akifumi Fujii, Takuto Kuramoto, Motoi Odani, Tadao Akizawa
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a major complication associated with chronic kidney disease. We evaluated the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, in Japanese haemodialysis patients with SHPT. METHODS: In this phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study, etelcalcetide was administered three times per week at an initial dose of 5 mg, and subsequently adjusted to doses between 2...
January 5, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28005175/research-on-kidney-and-mineral-metabolism-in-japan-past-present-and-future
#3
REVIEW
Masahide Mizobuchi, Hiroaki Ogata, Fumihiko Koiwa, Eriko Kinugasa, Tadao Akizawa
Since the identification of the kidney was the main site for the synthesis of calcitriol (1α, 25-dihydroxycholecalciferol), research on chronic kidney disease (CKD)-associated mineral metabolism disorders and their management has made rapid progress. Various active analogues of calcitriol have clinically become available for treating secondary hyperparathyroidism (SHPT), which is a representative mineral metabolism abnormality in CKD patients. A calcimimetic compound cinacalcet hydrochloride has also been developed for the medical management of SHPT through a different mechanism involving the calcium-sensing receptor...
December 22, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27998296/primary-hyperparathyroidism-in-pregnancy-treated-with-cinacalcet-a-case-report-and-review-of-the-literature
#4
Lara Vera, Silvia Oddo, Natascia Di Iorgi, Giorgio Bentivoglio, Massimo Giusti
BACKGROUND: The efficacy and safety of various modes of medical treatment for primary hyperparathyroidism in pregnancy are largely unknown. CASE PRESENTATION: We report the case of a 34-year-old white woman with primary hyperparathyroidism symptomatic for nephrolithiasis. Her serum calcium was 3.15 mmol/l and parathyroid hormone was 109.0 ng/L. Neck imaging found no pathological parathyroid tissue. Cinacalcet and cholecalciferol were started. She became pregnant 17 months later...
December 20, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27988213/down-regulation-of-abcg2-a-urate-exporter-by-parathyroid-hormone-enhances-urate-accumulation-in-secondary-hyperparathyroidism
#5
Ryusei Sugimoto, Hiroshi Watanabe, Komei Ikegami, Yuki Enoki, Tadashi Imafuku, Yoshiaki Sakaguchi, Michiya Murata, Kento Nishida, Shigeyuki Miyamura, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes...
December 14, 2016: Kidney International
https://www.readbyqxmd.com/read/27971362/exploring-the-potential-value-of-improved-care-for-secondary-hyperparathyroidism-shpt-with-a-novel-investigational-calcimimetic-therapy
#6
B Stollenwerk, S Iannazzo, K Cooper, V Belozeroff
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27941640/fibroblast-growth-factor-23-a-potential-uremic-toxin
#7
REVIEW
Piotr Kuczera, Marcin Adamczak, Andrzej Wiecek
Fibroblast growth factor-23 (FGF23) is a circulating member of the FGF family produced mainly by the osteocytes and osteoblasts that can act as a hormone. The main action of FGF23 is to lower phosphatemia via the reduction of urinary phosphate reabsorption and the decrease of 1,25(OH)₂-D generation in the kidney. In the course of chronic kidney disease (CKD), plasma FGF23 concentration rises early, most probably to compensate the inability of the deteriorating kidneys to excrete an adequate amount of phosphate...
December 8, 2016: Toxins
https://www.readbyqxmd.com/read/27900978/penile-calcific-uremic-arteriolopathy-occurring-postparathyroidectomy-in-a-hemodialysis-patient
#8
Salah Omar Bashir, Mahmoud A Aamer, Hayder A Omer, Mohamed D Morsy
Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare condition most frequently seen in patients with advanced chronic kidney disease. The clinical picture is characterized by painful skin lesions and ulcerations. The underlying pathology is medial calcification and intimal proliferation with microthrombi of small arteries. CUA is commonly associated with secondary hyperparathyroidism and high serum calcium and phosphate products. This article reports an atypical case where CUA developed after parathyroidectomy and in the course of treatment of hungry bone syndrome...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27900648/etelcalcetide-first-global-approval
#9
Hannah A Blair
Etelcalcetide (Parsabiv™) is a novel second generation calcimimetic agent developed by Amgen for the treatment of secondary hyperparathyroidism (SHPT), a complication of chronic kidney disease (CKD). Etelcalcetide reduces circulating levels of parathyroid hormone and calcium by binding directly to the calcium-sensing receptor. Intravenous etelcalcetide has been approved in the EU for the treatment of SHPT in adult patients with CKD on haemodialysis therapy. Regulatory applications for etelcalcetide in SHPT are also under review in the USA and Japan...
December 2016: Drugs
https://www.readbyqxmd.com/read/27880946/2md-dp001-a-single-agent-in-the-management-of-hemodialysis-patients-a-randomized-trial
#10
Ravi Thadhani, Julia B Zella, Danielle C Knutson, William J Blaser, Lori A Plum, Margaret Clagett-Dame, Raymond D Buck, Hector F DeLuca
BACKGROUND: Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented. METHODS: A multicenter, randomized, double-blind study compared DP001 to placebo in hemodialysis patients with serum-intact PTH (iPTH) ≥300 pg/ml...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/27873072/cinacalcet-hydrochloride-relieves-hypercalcemia-in-japanese-patients-with-parathyroid-cancer-and-intractable-primary-hyperparathyroidism
#11
Yasuhiro Takeuchi, Shunsuke Takahashi, Daishu Miura, Makoto Katagiri, Noriaki Nakashima, Hiroko Ohishi, Ryutaro Shimazaki, Yoshihiro Tominaga
Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases...
November 21, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/27836810/external-ca-2-regulates-polycystin-2-trpp2-cation-currents-in-llc-pk1-renal-epithelial-cells
#12
Xiao Qing Dai, Paula L Perez, Gonzalo Soria, Noelia Scarinci, Mariano Smoler, D Cristian Morsucci, Kunimasa Suzuki, María Del Rocío Cantero, Horacio F Cantiello
Polycystin-2 (PC2, TRPP2) is a nonselective cation channel whose dysfunction is associated with the onset of autosomal dominant polycystic kidney disease (ADPKD). PC2 contributes to Ca(2+) transport and cell signaling in renal epithelia and other tissues. Little is known however, as to the external Ca(2+) regulation of PC2 channel function. In this study, we explored the effect of external Ca(2+) on endogenous PC2 in wild type LLC-PK1 renal epithelial cells. We obtained whole cell currents at different external Ca(2+) concentrations, and observed that the basal whole cell conductance in normal Ca(2+)(1...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27796266/the-effectiveness-of-cinacalcet-as-an-adjunctive-therapy-for-hereditary-1-25-dihydroxyvitamin-d3-resistant-rickets
#13
Ayşehan Akıncı, İsmail Dündar, Meltem Kıvılcım
: High doses of oral calcium or long-term calcium infusions are recommended to correct the hypocalcemia and secondary hyperparathyroidism in patients with hereditary 1-25 dihydroxyvitamin D3 resistant rickets (HVDRR). Preliminary studies revealed that calcimimetics may be safe and effective therapeutic choise in children with secondary hyperparathyroidism. Our aim was to observe the efficacy of cinacalcet on the normalization of secondary hyperparathroidism and hypophosphatemia in two siblings with VDRR who did not respond to traditional therapy regimes...
October 31, 2016: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/27743301/recurrent-primary-hyperparathyroidism-due-to-type-1-parathyromatosis
#14
Monica Jain, David L Krasne, Frederick R Singer, Armando E Giuliano
Parathyromatosis is a rare condition consisting of multiple nodules of benign hyperfunctioning parathyroid tissue scattered throughout the neck and superior mediastinum. As a potential cause of recurrent or persistent hyperparathyroidism, parathyromatosis is a challenging condition to diagnose and treat. The optimal evaluation and management of patients with parathyromatosis is not well established. The reported case involves a patient who was initially diagnosed with primary hyperparathyroidism. The diagnosis of Type 1 parathyromatosis was made after the patient developed recurrent hyperparathyroidism with hypercalcemia and osteoporosis 17 years after the initial operation and underwent two additional operations...
October 14, 2016: Endocrine
https://www.readbyqxmd.com/read/27739473/associations-of-the-calcium-sensing-receptor-gene-casr-rs7652589-snp-with-nephrolithiasis-and-secondary-hyperparathyroidism-in-haemodialysis-patients
#15
Alicja E Grzegorzewska, Mateusz Paciorkowski, Adrianna Mostowska, Bartosz Frycz, Wojciech Warchoł, Ireneusz Stolarek, Marek Figlerowicz, Paweł P Jagodziński
Nephrolithiasis, secondary hyperparathyroidism (sHPT), and cardiovascular complications are associated with disturbances in Ca handling and contribute to morbidity/mortality during haemodialysis (HD). Calcimimetics, activators of the calcium-sensing receptor (CaSR), provide an effective means of reducing parathyroid hormone (PTH) secretion in sHPT. Polymorphism in CaSR gene (CASR) influences Ca-related parameters, however it was not shown in HD patients for CASR rs7652589. The minor allele at this polymorphism modifies the binding sites of transcription factors and CaSR expression...
October 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27725162/the-calcilytics-calhex-231-and-nps-2143-and-the-calcimimetic-calindol-reduce-vascular-reactivity-via-inhibition-of-voltage-gated-ca-2-channels
#16
Harry Z E Greenberg, Kazi S Jahan, Jian Shi, W-S Vanessa Ho, Anthony P Albert
The present study investigates the effect of commonly used negative and positive allosteric modulators of the calcium-sensing receptor (CaSR) on vascular reactivity. In wire myography studies, increasing [Ca(2+)]o from 1mM to 6mM induced concentration-dependent relaxations of methoxamine-induced pre-contracted rabbit mesenteric arteries, with 6mM [Ca(2+)]o producing almost complete relaxation. [Ca(2+)]o-induced relaxations were attenuated in the presence of the calcilytics Calhex-231 and NPS 2143, and abolished by the removal of the endothelium...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27692178/the-calcium-sensing-receptor-in-health-and-disease
#17
G Díaz-Soto, A Rocher, C García-Rodríguez, L Núñez, C Villalobos
The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca(2+) and by other physiological cations including Mg(2+), amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca(2+) homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca(2+) absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca(2+) metabolism...
2016: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/27658167/cinacalcet-versus-parathyroidectomy-in-the-treatment-of-secondary-hyperparathyroidism-post-renal-transplantation
#18
Amin R Soliman, Hoda A Maamoun, Mahmoud A Soliman, Hatem Darwish, Esam Elbanna
BACKGROUND: Persistent hyperparathyroidism (HPT) with hypercalcemia is prevalent after transplant and is considered a risk factor for progressive bone loss and fractures and vascular calcification, as well as the development of tubulointerstitial calcifications of renal allografts and graft dysfunction. The subtotal parathyroidectomy is the standard treatment, although currently it has been replaced by the calcimimetic cinacalcet. AIM: The hypothesis of this study is that subtotal parathyroidectomy is superior to cinacalcet for treatment of persistent secondary parathyroidectomy post renal transplant, with minimal morbidity and significantly it reduces the cost of treatment after transplantation...
September 1, 2016: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/27639083/population-pharmacokinetics-and-pharmacodynamics-of-the-calcimimetic-etelcalcetide-in-chronic-kidney-disease-and-secondary-hyperparathyroidism-receiving-hemodialysis
#19
P Chen, P Olsson Gisleskog, J J Perez-Ruixo, J Xiao, J Wilkins, A Narayanan, J P Gibbs, M Melhem
Etelcalcetide is a novel calcimimetic in development for the treatment of secondary hyperparathyroidism (SHPT). A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed relating etelcalcetide exposures to markers of efficacy (parathyroid hormone [PTH]) and safety (calcium) using data from three clinical studies. The semimechanistic model was developed that included allosteric activation pharmacology and understanding of calcium homeostasis. The temporal profiles for all biomarkers were well described by the model...
September 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27565442/calcium-sensing-receptor-effects-in-adipocytes-and-liver-cells-implications-for-an-adipose-hepatic-crosstalk
#20
Pia Villarroel, Pamela Mattar, Amanda D'Espessailles, Marco Arrese, Andrea Arreguin, Cecilia Fuentes, Marcela Reyes, Mariana Cifuentes
The calcium sensing receptor (CaSR) is expressed in human adipose cells, and its activation may associate with adipose tissue (AT) dysfunction. We evaluated whether CaSR stimulation influences adipocyte triglyceride (TG) and fatty acid binding protein 4 (aP2) content, and hepatocyte TGs and proinflammatory cytokine expression. The effect of the calcimimetic cinacalcet on TGs (fluorimetry), lipogenic genes (qPCR) and aP2 (immunoblot) was evaluated in LS14 adipocytes or AT. In the human HepG2 hepatic cell line, we assessed CaSR expression and cinacalcet effect on TGs and lipogenic and proinflammatory genes...
October 1, 2016: Archives of Biochemistry and Biophysics
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