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https://www.readbyqxmd.com/read/29344024/elevated-phosphate-levels-trigger-autophagy-mediated-cellular-apoptosis-in-h9c2-cardiomyoblasts
#1
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
#2
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
#3
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/29304096/exogenous-bmp7-in-aortae-of-rats-with-chronic-uremia-ameliorates-expression-of-profibrotic-genes-but-does-not-reverse-established-vascular-calcification
#4
Eva Gravesen, Maria Lerche Mace, Anders Nordholm, Jacob Hofman-Bang, Keith Hruska, Carsten Haagen Nielsen, Andreas Kjær, Klaus Olgaard, Ewa Lewin
Hyperphosphatemia and vascular calcification are frequent complications of chronic renal failure and bone morphogenetic protein 7 (BMP7) has been shown to protect against development of vascular calcification in uremia. The present investigation examined the potential reversibility of established uremic vascular calcification by treatment of uremic rats with BMP7. A control model of isogenic transplantation of a calcified aorta from uremic rats into healthy littermates examined whether normalization of the uremic environment reversed vascular calcification...
2018: PloS One
https://www.readbyqxmd.com/read/29291028/safety-and-efficacy-of-ferric-citrate-in-phosphate-reduction-and-iron-supplementation-in-patients-with-chronic-kidney-disease
#5
Mei-Yi Wu, Ying-Chun Chen, Chun-Hung Lin, Yun-Chun Wu, Yu-Kang Tu, Der-Cherng Tarng
Ferric citrate has been reported to have the potential to reduce phosphate and increase iron availability in patients with chronic kidney disease. In the present study, we evaluated its safety and efficacy in phosphate reduction and iron supplementation in chronic kidney disease stage 3-5 requiring dialysis patients. We systematically searched for clinical trials published in PubMed, Medline, and Cochrane databases. Only randomized controlled trials on the effects of ferric citrate in chronic kidney disease stage 3-5 requiring dialysis patients were selected...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29240673/urinary-fractional-excretion-of-phosphorus-in-dogs-with-spontaneous-chronic-kidney-disease
#6
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/29238578/bone-eating-kidney-disease
#7
Abhilash Koratala, Muhannad Leghrouz, Amir Kazory
In the current era of early detection of chronic kidney disease and efficient therapeutic options for management of its complications, skeletal manifestations of renal hyperparathyroidism are increasingly rare. A 31-year-old female patient presented for evaluation of severe pain in the left forearm, right hand, right knee, right hip, and lower back following a fall sustained 3 days prior to presentation. She had a history of end-stage renal disease and received maintenance hemodialysis. Review of the medical records revealed that she had poor compliance with her diet, medications, and dialysis treatments...
2017: SAGE Open Medical Case Reports
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
#8
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
#9
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/29190606/association-between-klotho-gene-polymorphism-and-markers-of-bone-metabolism-in-patients-receiving-maintenance-hemodialysis-in-iran
#10
Aboalfazl Nazarian, Meisam Hasankhani, Monireh Aghajany-Nasab, Ali Monfared
INTRODUCTION: Some genetic variations of Klotho have been reported as a risk factor for calcification and hyperphosphatemia in chronic kidney disease. Klotho polymorphism is also associated with outcome in patients receiving hemodialysis. This study aimed to evaluate the relationship between Klotho single nucleotide polymorphism (SNP) and bone metabolism as an early prognostic measure for chronic kidney disease.   Materials and Methods. Sixty patients receiving hemodialysis and 60 age-matched controls were enrolled in the study of the assessment of 2 types of Klotho polymorphism (G395A and C1818T)...
November 2017: Iranian Journal of Kidney Diseases
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/29128884/effect-of-npt2b-deletion-on-intestinal-and-renal-inorganic-phosphate-pi-handling
#14
Kayo Ikuta, Hiroko Segawa, Shohei Sasaki, Ai Hanazaki, Toru Fujii, Aoi Kushi, Yuka Kawabata, Ruri Kirino, Sumire Sasaki, Miwa Noguchi, Ichiro Kaneko, Sawako Tatsumi, Otoya Ueda, Naoko A Wada, Hiromi Tateishi, Mami Kakefuda, Yosuke Kawase, Shuichi Ohtomo, Yasuhiro Ichida, Akira Maeda, Kou-Ichi Jishage, Naoshi Horiba, Ken-Ichi Miyamoto
BACKGROUND: Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na(+)-dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. METHODS: In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption...
November 11, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29056165/the-leaky-gut-and-altered-microbiome-in-chronic-kidney-disease
#15
Wei Ling Lau, Nosratola D Vaziri
Chronic kidney disease results in disruption of the intestinal epithelial barrier as well as profound changes in the gut microbial flora. These events are largely mediated by (1) heavy influx of circulating urea to the gut lumen and (2) dietary restrictions of foods containing high fiber (such as fruits and vegetable) and symbiotic organisms (such as yogurt and cheese) imposed to mitigate hyperkalemia and hyperphosphatemia. Collectively, these factors promote systemic inflammation and cardiovascular morbidity by mediating microbial dysbiosis, disruption of the intestinal epithelial barrier, and translocation of endotoxin, bacterial fragments, and uremic toxins across the "leaky gut" into the bloodstream...
November 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
#16
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
#17
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
#18
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/28857396/hyperphosphatemia-induces-senescence-in-human-endothelial-cells-by-increasing-endothelin-1-production
#19
Gemma Olmos, Patricia Martínez-Miguel, Elena Alcalde-Estevez, Diana Medrano, Patricia Sosa, Leocadio Rodríguez-Mañas, Manuel Naves-Diaz, Diego Rodríguez-Puyol, María Piedad Ruiz-Torres, Susana López-Ongil
Hyperphosphatemia is related to some pathologies, affecting vascular cell behavior. This work analyzes whether high concentration of extracellular phosphate induces endothelial senescence through up-regulation of endothelin-1 (ET-1), exploring the mechanisms involved. The phosphate donor β-glycerophosphate (BGP) in human endothelial cells increased ET-1 production, endothelin-converting enzyme-1 (ECE-1) protein, and mRNA expression, which depend on the AP-1 activation through ROS production. In parallel, BGP also induced endothelial senescence by increasing p16 expression and the senescence-associated β-galactosidase (SA-ß-GAL) activity...
December 2017: Aging Cell
https://www.readbyqxmd.com/read/28843411/the-activin-receptor-is-stimulated-in-the-skeleton-vasculature-heart-and-kidney-during-chronic-kidney-disease
#20
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...
August 23, 2017: Kidney International
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