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Hyperphosphatemia in CKD

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https://www.readbyqxmd.com/read/29415929/-pharmacological-pharmaceutical-and-clinical-profiles-of-sucroferric-oxyhydroxide-p-tol%C3%A2-chewable-tab-250%C3%A2-mg-500%C3%A2-mg-a-therapeutic-agent-for-hyperphosphatemia
#1
Satoshi Tatemichi, Fumiaki Nakagaki, Shoichi Yoshioka, Natsuko Shichiri
Sucroferric oxyhydroxide (P-TOL® chewable tablets, 250 and 500 mg) is a phosphate binder for oral use; it is composed of polynuclear iron (III)-oxyhydroxide, sucrose, and starches, and is currently indicated for alleviating hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. The results of non-clinical pharmacological studies have suggested that P-TOL consistently decreases serum phosphorus levels in the aqueous environment at pH levels similar to those in the gastrointestinal tract, thereby suppressing the progression of secondary hyperparathyroidism, aberrant calcification, and abnormal bone metabolism associated with hyperphosphatemia...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29409087/-chronic-kidney-disease-update-2018
#2
Markus Ketteler, Christoph Wanner
SGLT2-INHIBITION IN DIABETIC AND NON-DIABETIC KIDNEY DISEASE: The CANVAS Program Collaborative Group study confirmed nephroprotective actions by canagliflocin comparable to empagliflozin as published in the EMPA-REG Outcome study. Treatment with Liraglutide (LEADER study) also suggests nephroprotection via albuminuria reduction a decreased eGFR decline in subgroups and depending on stages of diabetic nephropathy. KDIGO CKD-MBD GUIDELINE UPDATE 2017: In July 2017, an update of the KDIGO (Kidney Disease: Improving Global Outcomes) 2009 guideline on diagnostic and treatment chronic kidney disease - mineral and bone disorders (CKD-MBD) was published...
February 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29372301/effect-of-variations-in-dietary-pi-intake-on-intestinal-pi-transporters-napi-iib-pit-1-and-pit-2-and-phosphate-regulating-factors-pth-fgf-23-and-mepe
#3
Tatiana Martins Aniteli, Flávia Ramos de Siqueira, Luciene Machado Dos Reis, Wagner Vasques Dominguez, Elizabeth Maria Costa de Oliveira, Patrícia Castelucci, Rosa Maria Affonso Moysés, Vanda Jorgetti
Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (Pi) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent Pi absorption is modulated by dietary Pi. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary Pi concentration over 2 days would alter hormones involved in Pi metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine...
January 25, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29357413/defective-interplay-between-mtorc1-activity-and-endoplasmic-reticulum-stress-unfolded-protein-response-in-uremic-vascular-calcification
#4
Dibyendu Panda, Xiuying Bai, Yves Sabbagh, Yan Zhang, Hans-Christian Zaun, Angeliki Karellis, Antonis E Koromilas, Mark Lipman, Andrew C Karaplis
Vascular calcification increases the risk of cardiovascular disease and death in patients with chronic kidney disease (CKD). Increased activity of the mammalian target of rapamycin complex 1 (mTORC1) and endoplasmic reticulum (ER) stress-unfolded protein response (UPR) are reported to partake independently in the pathogenesis of vascular calcification in CKD. However, the association between mTORC1 activity and ER stress-UPR remains unknown. We report here that components of the uremic state (activation of the receptor for advanced glycation end-products (RAGE) or hyperphosphatemia) potentiate vascular smooth muscle cell (VSMC) calcification by inducing persistent and exaggerated activity of mTORC1...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29344024/elevated-phosphate-levels-trigger-autophagy-mediated-cellular-apoptosis-in-h9c2-cardiomyoblasts
#5
Yao-Lung Liu, Kuan-Ho Lin, Shanmugam Tamilselvi, Wei-Kung Chen, Chia-Yao Shen, Ray-Jade Chen, Cecilia Hsuan Day, Hsi-Chin Wu, Vijaya Padma Viswanadha, Chih-Yang Huang
BACKGROUND/AIM: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. METHODS: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract...
December 2017: Cardiorenal Medicine
https://www.readbyqxmd.com/read/29340316/npt-iib-inhibition-does-not-improve-hyperphosphatemia-in-ckd
#6
Tobias E Larsson, Chisato Kameoka, Ikumi Nakajo, Yuta Taniuchi, Satoshi Yoshida, Tadao Akizawa, Ronald A Smulders
Introduction: Serum phosphate levels are insufficiently controlled in many patients with end-stage renal disease (ESRD), and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the efficacy, safety, tolerability, and pharmacokinetics of the novel and specific small molecule NPT-IIb inhibitor ASP3325 for the first time in humans. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 1a single (n = 88) and multiple (n = 36) ascending dose study in healthy subjects, and a randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17)...
January 2018: KI Reports
https://www.readbyqxmd.com/read/29319766/epic-trial-education-programme-impact-on-serum-phosphorous-control-in-ckd-5d-patients-on-hemodialysis
#7
Carmen Tzanno Branco Martins, Bárbara Margareth Menardi Biavo, Clarissa Baia Bargas Uezima, Jacqueline Alves Pereira Dos Santos, Camila Machado de Barros, Elzo Ribeiro Júnior, Paul Clesca Troconis, Cristoforo Scavone, Marcus Vinicius de Souza João Luiz
INTRODUCTION: In stage 5D chronic kidney disease (CKD 5D) patients, the encouragement of treatment adherence by health professionals is a significant clinical challenge. OBJECTIVES: This study evaluates the impact of a nutritional education programme on hyperphosphatemia, utilizing the transtheoretical model of behavior change (TMBC). SUBJECTS AND METHODS: A prospective interventional study comprising 179 CKD 5D patients with hypophosphatemia...
October 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29240673/urinary-fractional-excretion-of-phosphorus-in-dogs-with-spontaneous-chronic-kidney-disease
#8
Cínthia Ribas Martorelli, Márcia Mery Kogika, Fernanda Chicharo Chacar, Douglas Segalla Caragelasco, Ana Carolina Brandão de Campos Fonseca Pinto, Carla Aparecida Batista Lorigados, Lúcia Conceição Andrade
The increase of urinary fractional excretion of phosphorus (uFEP) may indicate phosphorus retention before the onset of hyperphosphatemia in the early stages of chronic kidney disease (CKD). The hypothesis of this study is whether uFEP may increase during the early stage of CKD as a compensatory mechanism to prevent hyperphosphatemia as well as whether hyperphosphatemia in the late stages is associated with increase or decrease in uFEP in dogs with naturally occurring CKD; therefore, the aim of this study was to determine the uFEP in CKD dogs with different stages...
December 14, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/29227975/high-phosphate-induced-calcification-of-vascular-smooth-muscle-cells-is-associated-with-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#9
Daohai Zhang, Xianjin Bi, Yong Liu, Yinghui Huang, Jiachuan Xiong, Xinli Xu, Tangli Xiao, Yanlin Yu, Wei Jiang, Yunjian Huang, Jingbo Zhang, Bo Zhang, Jinghong Zhao
BACKGROUND/AIMS: Hyperphosphatemia is one of the most notable features of chronic kidney disease (CKD). Numerous epidemiological and clinical studies have found that high serum phosphate concentrations are associated with calcification in the coronary arteries. However, the mechanisms underlying the vascular calcification induced by high phosphate have not been understood fully. METHODS: Vascular smooth muscle cells (VSMCs) were cultured in high-phosphate media to induce vascular calcification, which was detected by Alizarin red S staining...
December 8, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29197521/high-phosphate-induced-downregulation-of-ppar%C3%AE-contributes-to-ckd-associated-vascular-calcification
#10
Liang Liu, Yong Liu, Ying Zhang, Xianjin Bi, Ling Nie, Chi Liu, Jiachuan Xiong, Ting He, Xinlin Xu, Yanlin Yu, Ke Yang, Jun Gu, Yunjian Huang, Jingbo Zhang, Zhiren Zhang, Bo Zhang, Jinghong Zhao
Medial arterial calcification associated with hyperphosphatemia is a main cause of cardiovascular mortality in patients with chronic kidney disease (CKD), but the mechanisms underlying high phosphate-induced vascular calcification remain largely unknown. Here, we observed a significant decrease in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in calcified arteries both in CKD patients and in a mouse model of CKD with hyperphosphatemia. In vitro, high phosphate treatment led to a decreased expression of PPARγ in mouse vascular smooth muscle cells (VMSCs), accompanied by apparent osteogenic differentiation and calcification...
November 29, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29186198/safety-and-efficacy-of-ferric-citrate-in-patients-with-nondialysis-dependent-chronic-kidney-disease
#11
Glenn M Chertow, Geoffrey A Block, John F Neylan, Pablo E Pergola, Katrin Uhlig, Steven Fishbane
Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/29146611/smooth-muscle-selective-nuclear-factor-%C3%AE%C2%BAb-inhibition-reduces-phosphate-induced-arterial-medial-calcification-in-mice-with-chronic-kidney-disease
#12
Tadashi Yoshida, Maho Yamashita, Chihiro Horimai, Matsuhiko Hayashi
BACKGROUND: Hyperphosphatemia is a major factor promoting the formation of arterial medial calcification in chronic kidney disease (CKD). However, arterial medial calcification begins to occur during the early stages of CKD, when hyperphosphatemia is not yet apparent. It is predicted that other factors also play a role. The aim of the present study was to determine the role of pro-inflammatory nuclear factor-κB (NF-κB) signaling in smooth muscle cells (SMCs) for phosphate-induced arterial medial calcification in CKD mice...
November 16, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29146137/the-impact-of-additives-on-the-phosphorus-potassium-and-sodium-content-of-commonly-consumed-meat-poultry-and-fish-products-among-patients-with-chronic-kidney-disease
#13
Arti Sharma Parpia, Mary L'Abbé, Marc Goldstein, Joanne Arcand, Bernadene Magnuson, Pauline Darling
OBJECTIVE: Patients with chronic kidney disease (CKD) are advised to limit their dietary intake of phosphorus and potassium as hyperphosphatemia and hyperkalemia are both associated with an increased risk of mortality. There is uncertainty concerning the actual content of these minerals in the Canadian food supply, as phosphorus and potassium are increasingly being used as food additives. This study aimed to determine the impact of food additives on the chemically analyzed content of phosphorus, potassium, sodium, and protein in commonly consumed meat, poultry, and fish products (MPFs)...
November 14, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/28939042/inorganic-phosphate-induced-impairment-of-osteoclast-cell-cell-fusion-by-the-inhibition-of-ap-1-mediated-dc-stamp-expression
#14
Masaki Arioka, Fumi Takahashi-Yanaga, Narihito Tatsumoto, Toshiyuki Sasaguri
Chronic kidney disease (CKD) causes hyperphosphatemia and secondary hyperparathyroidism, leading to several disorders of bone metabolism. Although high concentrations of extracellular inorganic phosphate (Pi) inhibit osteoclastogenesis, the molecular mechanism of this effect has not been fully understood. In the present study, therefore, we examined the effect of Pi on the differentiation of the osteoclast precursor RAW-D cells. Treatment with the receptor activator of nuclear factor-kappa B ligand induced the differentiation of RAW-D cells (osteoclastogenesis)...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#15
REVIEW
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28900759/efficacy-and-safety-of-sevelamer-carbonate-in-hyperphosphatemic-pediatric-patients-with-chronic-kidney-disease
#16
Sahar Fathallah-Shaykh, Dorota Drozdz, Joseph Flynn, Randall Jenkins, Katherine Wesseling-Perry, Sarah J Swartz, Craig Wong, Beverly Accomando, Gerald F Cox, Bradley A Warady
BACKGROUND: Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosphorus intake, dialysis, and treatment with oral phosphate binders, none of which were approved by the Federal Food and Drug Administration in pediatric patients at the time of this study. METHODS: This was a phase 2, multicenter study (NCT01574326) with a 2-week, randomized, placebo-controlled, fixed-dose period (FDP) followed by a 6-month, single-arm, open-label, dose-titration period (DTP), with the aim to evaluate the safety and efficacy of sevelamer carbonate (SC) in hyperphosphatemic pediatric patients with CKD...
September 12, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28843411/the-activin-receptor-is-stimulated-in-the-skeleton-vasculature-heart-and-kidney-during-chronic-kidney-disease
#17
Matthew J Williams, Toshifumi Sugatani, Olga A Agapova, Yifu Fang, Joseph P Gaut, Marie-Claude Faugere, Hartmut H Malluche, Keith A Hruska
We examined activin receptor type IIA (ActRIIA) activation in chronic kidney disease (CKD) by signal analysis and inhibition in mice with Alport syndrome using the ActRIIA ligand trap RAP-011 initiated in 75-day-old Alport mice. At 200 days of age, there was severe CKD and associated Mineral and Bone Disorder (CKD-MBD), consisting of osteodystrophy, vascular calcification, cardiac hypertrophy, hyperphosphatemia, hyperparathyroidism, elevated FGF23, and reduced klotho. The CKD-induced bone resorption and osteoblast dysfunction was reversed, and bone formation was increased by RAP-011...
January 2018: Kidney International
https://www.readbyqxmd.com/read/28843391/-management-of-bone-and-mineral-metabolism-disorders-before-the-dialysis-stage-remains-still-perfectible-data-from-the-french-phosphorus-and-calcium-survey-photo-graphe
#18
Guillaume Jean, Éric Daugas, Hubert Roth, Tilman Drueke, Jean-Louis Bouchet, Thierry Hannedouche, Gérard London, Denis Fouque
Only limited data is available on the management of the chronic kidney disease-associated bone and mineral metabolism disorder (CKD-MBD) in the pre-dialysis stages of CKD in France. A better knowledge of current management habits could lead to an improvement in the implementation of international recommendations (KDIGO). The 3rd version of the French Phosphorus and Calcium Survey Photo-Graphe (Sanofi) included a cohort of CKD stages 4 and 5 patients, whose aim was to examine the prevalence of CKD-MBD and the quality of its management in patients under the care of 62 nephrologists from over 20 geographical regions in France...
August 23, 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28795324/the-fgf23-klotho-axis-and-cardiac-tissue-doppler-imaging-in-pediatric-chronic-kidney-disease-a-prospective-cohort-study
#19
Ylva Tranæus Lindblad, Hannes Olauson, Georgios Vavilis, Ulf Hammar, Maria Herthelius, Jonas Axelsson, Peter Bárány
BACKGROUND: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. METHODS: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1...
August 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28776684/characterization-and-assessment-of-potential-micrornas-involved-in-phosphate-induced-aortic-calcification
#20
Maya Fakhry, Najwa Skafi, Mohammad Fayyad-Kazan, Firas Kobeissy, Eva Hamade, Saida Mebarek, Aida Habib, Nada Borghol, Asad Zeidan, David Magne, Hussein Fayyad-Kazan, Bassam Badran
Medial artery calcification, a hallmark of type 2 diabetes mellitus and chronic kidney disease (CKD), is known as an independent risk factor for cardiovascular mortality and morbidity. Hyperphosphatemia associated with CKD is a strong stimulator of vascular calcification but the molecular mechanisms regulating this process remain not fully understood. We showed that calcification was induced after exposing Sprague-Dawley rat aortic explants to high inorganic phosphate level (Pi , 6 mM) as examined by Alizarin red and Von Kossa staining...
August 4, 2017: Journal of Cellular Physiology
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