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https://www.readbyqxmd.com/read/27900978/penile-calcific-uremic-arteriolopathy-occurring-postparathyroidectomy-in-a-hemodialysis-patient
#1
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
#2
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...
November 29, 2016: Drugs
https://www.readbyqxmd.com/read/27880946/2md-dp001-a-single-agent-in-the-management-of-hemodialysis-patients-a-randomized-trial
#3
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...
November 24, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27873072/cinacalcet-hydrochloride-relieves-hypercalcemia-in-japanese-patients-with-parathyroid-cancer-and-intractable-primary-hyperparathyroidism
#4
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
#5
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...
November 9, 2016: 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
#6
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
#7
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
#8
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
#9
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...
October 8, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27692178/the-calcium-sensing-receptor-in-health-and-disease
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27526425/-treatment-of-secondary-hyperparathyroidism-in-hemodialysed-patients-paricalcitol-with-or-without-cinacalcet
#14
Jacek Zawierucha, Jolanta Małyszko, Jacek Małyszko, Teresa Dryl-Rydzyńska, Tomasz Prystacki, Wojciech Marcinkowski
Secondary hyperparathyroidism (sHPT) is a common complication being a consequence of metabolic disorders associated with chronic kidney disease (CKD). Treatment of the sHPT should lead to calcium-phosphate management stabilization and parathyroid hormone levels reduction. The phosphate binders, synthetic vitamin D analogs and calcimimetics are used in sHPT treatment. In this paper we analyzed the results of three month paricalcitol treatment of 36 hemodialysis patients with sHPT (serum iPTH> 500 pg/ml). 11 patients have additionally received cinacalcet...
2016: Przegla̧d Lekarski
https://www.readbyqxmd.com/read/27520998/successful-treatment-of-recurrent-renal-stones-with-cinacalcet-in-a-patient-with-primary-hyperparathyroidism
#15
Priyesh Chauhan, Neil J Gittoes, Tarekegn Geberhiwot
A man aged 72 years with long-standing primary hyperparathyroidism (HPT), a background of recurrent bilateral renal stones and failed parathyroid surgery is described. During the 27 months preceding treatment, episodes of renal colic became increasingly frequent and he required multiple surgical interventions. Given the lack of medical therapies to definitively treat his symptoms, he was started on a trial of the calcimimetic, Cinacalcet. Cinacalcet has previously been shown to reduce hypercalcaemia in patients with primary HPT...
2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27517676/pharmacokinetics-biotransformation-and-excretion-of-14-c-etelcalcetide-amg-416-following-a-single-microtracer-intravenous-dose-in-patients-with-chronic-kidney-disease-on-hemodialysis
#16
Raju Subramanian, Xiaochun Zhu, M Benjamin Hock, Bethlyn J Sloey, Benjamin Wu, Sarah F Wilson, Ogo Egbuna, J Greg Slatter, Jim Xiao, Gary L Skiles
Etelcalcetide (AMG 416) is a novel synthetic peptide calcium-sensing receptor activator in clinical development as an intravenous calcimimetic for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. Etelcalcetide is composed of seven D-aminoacids with an L-cysteine linked to a D-cysteine by a disulfide bond. A single intravenous dose of [(14)C]etelcalcetide (10 mg; 26.3 kBq; 710 nCi) was administered to patients with CKD on hemodialysis to elucidate the pharmacokinetics, biotransformation, and excretion of etelcalcetide in this setting...
August 12, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27479950/hyperparathyroidism-of-renal-disease
#17
REVIEW
Noah K Yuen, Shubha Ananthakrishnan, Michael J Campbell
Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Patients with rHPT experience increased rates of cardiovascular problems and bone disease. The Kidney Disease: Improving Global Outcomes guidelines recommend that screening and management of rHPT be initiated for all patients with chronic kidney disease stage 3 (estimated glomerular filtration rate, < 60 mL/min/1...
2016: Permanente Journal
https://www.readbyqxmd.com/read/27459979/impact-of-the-introduction-of-calcimimetics-on-timing-of-parathyroidectomy-in-secondary-and-tertiary-hyperparathyroidism
#18
Willemijn Y van der Plas, Anton F Engelsman, Akin Özyilmaz, Anouk N van der Horst-Schrivers, Kornelis Meijer, Gooitzen M van Dam, Robert A Pol, Martin H de Borst, Schelto Kruijff
BACKGROUND: Hyperparathyroidism (HPT), both secondary and tertiary, is common in patients with end-stage renal disease, and is associated with severe bone disorders, cardiovascular complications, and increased mortality. Since the introduction of calcimimetics in 2004, treatment of HPT has shifted from surgery to predominantly medical therapy. OBJECTIVE: The aim of this study was to evaluate the impact of this change of management on the HPT patient population before undergoing (sub-)total parathyroidectomy (PTx)...
July 26, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27296065/sulfinamide-phosphinates-as-chiral-catalysts-for-the-enantioselective-organocatalytic-reduction-of-imines
#19
Ahmed Chelouan, Rocío Recio, Lorenzo G Borrego, Eleuterio Álvarez, Noureddine Khiar, Inmaculada Fernández
A new type of chiral sulfinamide phosphinate catalysts with up to three stereogenic centers, readily accessible from commercially available starting materials, is reported. The naphthyl derivative SulPhos proved to be highly efficient in the organocatalytic asymmetric imine reduction, leading to a wide range of arylmethylamines in high yields with up to 99% ee under 10% catalyst loading. The synthetic utility of this method was demonstrated by the expeditious enantioselective synthesis of the calcimimetic NPS-R568...
July 1, 2016: Organic Letters
https://www.readbyqxmd.com/read/27230839/-pharmacological-characteristics-of-drugs-targeted-on-calcium-sensing-receptor-properties-of-cinacalcet-hydrochloride-as-allosteric-modulator
#20
Nobuo Nagano, Takaaki Tsutsui
Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects...
June 2016: Clinical Calcium
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