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Fgf23-klotho

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https://www.readbyqxmd.com/read/28795324/the-fgf23-klotho-axis-and-cardiac-tissue-doppler-imaging-in-pediatric-chronic-kidney-disease-a-prospective-cohort-study
#1
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/28761977/calcineurin-inhibitors-regulate-fibroblast-growth-factor-23-fgf23-synthesis
#2
Ludmilla Bär, Claudia Großmann, Michael Gekle, Michael Föller
Fibroblast growth factor 23 (FGF23) inhibits renal phosphate reabsorption and calcitriol formation, effects depending on Klotho as a co-receptor for FGF23. In addition, FGF23/Klotho strongly influences aging and the onset of age-associated diseases. The synthesis of FGF23 by bone cells is induced by store-operated Ca(2+) entry (SOCE) through Orai1 in UMR106 osteoblast-like cells. Ca(2+) entry activates the phosphatase calcineurin in many cell types which dephosphorylates nuclear factor of activated T cells (NFAT) thereby stimulating its transcriptional activity...
July 31, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28728941/comparison-of-calcimimetic-r568-and-calcitriol-in-mineral-homeostasis-in-the-hyp-mouse-a-murine-homolog-of-x-linked-hypophosphatemia
#3
Maren Leifheit-Nestler, Julia Kucka, Emi Yoshizawa, Geert Behets, Patrick D'Haese, Christian Bergen, Martin Meier, Dagmar-Christiane Fischer, Dieter Haffner
X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)2D3 (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health...
July 18, 2017: Bone
https://www.readbyqxmd.com/read/28600880/klotho-lacks-an-fgf23-independent-role-in-mineral-homeostasis
#4
Olena Andrukhova, Jessica Bayer, Christiane Schüler, Ute Zeitz, Sathish K Murali, Sibel Ada, Jose M Alvarez-Pez, Alina Smorodchenko, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating vitamin D hormone production and renal handling of minerals by signaling through an FGF receptor/αKlotho (Klotho) receptor complex. Whether Klotho has FGF23-independent effects on mineral homeostasis is a controversial issue. Here, we aimed to shed more light on this controversy by comparing male and female triple knockout mice with simultaneous deficiency in Fgf23 and Klotho and a nonfunctioning vitamin D receptor (VDR) (Fgf23/Klotho/VDR) with double (Fgf23/VDR, Klotho/VDR, and Fgf23/Klotho) and single Fgf23, Klotho, and VDR mutants...
June 10, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28558021/interactions-of-sclerostin-with-fgf23-soluble-klotho-and-vitamin-d-in-renal-transplantation
#5
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Cristiana Leonangeli, Alessio Farcomeni, Valeria Fassino, Sandro Mazzaferro
Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D)...
2017: PloS One
https://www.readbyqxmd.com/read/28288230/-somatotropic-axis-and-molecular-markers-of-mineral-metabolism-in-children-undergoing-chronic-peritoneal-dialysis
#6
María Luisa Ceballos Osorio, Francisco Cano Schuffeneger
Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. OBJECTIVES: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. PATIENTS AND METHOD: A longitudinal 12-month follow-up in prepuberal PD children...
February 2017: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/28212442/ecto-5-nucleotidase-cd73-nt5e-vitamin-d-receptor-and-fgf23-gene-polymorphisms-may-play-a-role-in-the-development-of-calcific-uremic-arteriolopathy-in-dialysis-patients-data-from-the-german-calciphylaxis-registry
#7
Hansjörg Rothe, Vincent Brandenburg, Margot Haun, Barbara Kollerits, Florian Kronenberg, Markus Ketteler, Christoph Wanner
INTRODUCTION: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. METHODS: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD)...
2017: PloS One
https://www.readbyqxmd.com/read/28134398/-new-biomarkers-of-ckd-mbd
#8
Marzia Pasquali, Lida Tartaglione, Silverio Rotondi
Chronic kidney failure involves abnormalities of mineral metabolism, skeletal and of cardiovascular system (so called CKD - MBD) that have a major impact on the survival of renal patient. Increasingly complex pathophysiological mechanisms have been discovered in recent years with evidence of new molecules involved in the development of CKD - MBD. Besides the classical PTH / Vitamin D axis, the most recent discovery of a new FGF23 / Klotho axis has expanded knowledge on the mechanisms of mineral homeostasis but also on the more complex mechanisms of cellular aging, vascular calcification and cardiac remodeling...
November 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28095739/expression-and-localization-of-fibroblast-growth-factor-fgf-23-and-klotho-in-the-spleen-its-physiological-and-functional-implications
#9
Yuri Nakashima, Toru Mima, Mitsuru Yashiro, Tomohiro Sonou, Masaki Ohya, Asuka Masumoto, Shintaro Yamanaka, Daisuke Koreeda, Koichi Tatsuta, Yoshiyuki Hanba, Mari Moribata, Shigeo Negi, Takashi Shigematsu
The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220(+) CD21/CD35(+) CD1d(+) CD43(-) marginal zone B cells...
January 18, 2017: Growth Factors
https://www.readbyqxmd.com/read/27746322/genetic-diseases-resulting-from-disordered-fgf23-klotho-biology
#10
REVIEW
Michael J Econs
No abstract text is available yet for this article.
October 13, 2016: Bone
https://www.readbyqxmd.com/read/27659551/-somatotropic-axis-and-molecular-markers-of-mineral-metabolism-in-children-undergoing-chronic-peritoneal-dialysis
#11
María Luisa Ceballos Osorio, Francisco Cano Schuffeneger
Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. OBJECTIVES: 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. PATIENTS AND METHOD: A longitudinal 12-month follow-up in prepuberal PD children...
September 19, 2016: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/27622885/fgf23-klotho-signaling-axis-in-the-kidney
#12
REVIEW
Reinhold G Erben, Olena Andrukhova
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone protecting against the potentially deleterious effects of hyperphosphatemia by suppression of phosphate reabsorption and of active vitamin D hormone synthesis in the kidney. The kidney is one of the main target organs of FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23-Klotho signaling in the kidney. During recent years, it has become clear that FGF23 acts independently on proximal and distal tubular epithelium...
July 2017: Bone
https://www.readbyqxmd.com/read/27378183/loss-of-function-of-napiiia-causes-nephrocalcinosis-and-possibly-kidney-insufficiency
#13
Dganit Dinour, Miriam Davidovits, Liat Ganon, Justyna Ruminska, Ian C Forster, Nati Hernando, Eran Eyal, Eli J Holtzman, Carsten A Wagner
BACKGROUND: Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency. METHODS: Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly...
July 4, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27312441/turning-over-renal-osteodystrophy-dogma-direct-actions-of-fgf23-on-osteoblast-%C3%AE-catenin-pathway
#14
Susan C Schiavi, Rosa M A Moysés
Although recognized as a major complication of chronic kidney disease (CKD), the pathophysiology of the CKD-related mineral and bone disorder (CKD-MBD) is not completely understood. Recently, the inhibition of Wnt/β-catenin pathway in osteocytes by sclerostin has been shown to play a role in CKD-MBD. The study by Carrilo-Lopez et al. confirms this inhibition in an experimental model of CKD. Moreover, they describe direct actions of FGF23-Klotho on osteoblasts, increasing the expression of DKK1, another Wnt/β-catenin pathway inhibitor...
July 2016: Kidney International
https://www.readbyqxmd.com/read/27220755/fibroblast-growth-factor-23-modifies-the-pharmacological-effects-of-angiotensin-receptor-blockade-in-experimental-renal-fibrosis
#15
Maarten A de Jong, Katarina Mirkovic, Rik Mencke, Joost G Hoenderop, René J Bindels, Marc G Vervloet, Jan-Luuk Hillebrands, Jacob van den Born, Gerjan Navis, Martin H de Borst
Background: Blockade of the renin-angiotensin-aldosterone system (RAAS) retards progression of chronic kidney disease. Yet, in many patients, the renoprotective effect is incomplete. A high circulating level of the phosphaturic hormone fibroblast growth factor 23 is associated with an impaired response to RAAS blockade-based therapy in clinical studies. Therefore, we addressed whether administration of recombinant fibroblast growth factor 23 (FGF23) interferes with the efficacy of angiotensin receptor blocker (ARB) treatment in a mouse model of renal fibrosis [unilateral ureteral obstruction (UUO)]...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27215557/klotho-the-holy-grail-of-the-kidney-from-salt-sensitivity-to-chronic-kidney-disease
#16
REVIEW
Rigas G Kalaitzidis, Anila Duni, Kostas C Siamopoulos
The Klotho gene displays an extremely shortened life span with loss of function missense mutations leading to premature multiple organ failure, thus resembling human premature aging syndromes. The transmembrane form of Klotho protein functions as an obligatory co-receptor for FGF23. Klotho and FGF23 are crucial components for the regulation of vitamin D metabolism and subsequently blood phosphate levels. The secreted Klotho protein has multiple regulatory functions, including effects on electrolyte homeostasis, on growth factor pathways as well as on oxidative stress, which are currently the object of extensive research...
October 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27125741/the-fgf23-klotho-regulatory-network-and-its-roles-in-human-disorders
#17
S Kinoshita, M Kawai
The functions of Klotho (KL) are multifaceted and include the regulation of aging and mineral metabolism. It was originally identified as the gene responsible for premature aging-like symptoms in mice and was subsequently shown to function as a coreceptor in the fibroblast growth factor (FGF) 23 signaling pathway. The discovery of KL as a partner for FGF23 led to significant advances in understanding of the molecular mechanisms underlying phosphate and vitamin D metabolism, and simultaneously clarified the pathogenic roles of the FGF23 signaling pathway in human diseases...
2016: Vitamins and Hormones
https://www.readbyqxmd.com/read/26943611/the-fgf23-klotho-axis-in-the-regulation-of-mineral-and-metabolic-homeostasis
#18
REVIEW
Masanobu Kawai
The function of fibroblast growth factor (FGF) 23 has been suggested to be multifaceted beyond its canonical function as a regulator of mineral metabolism. FGF23 was originally shown to play a central role in phosphate (Pi) and vitamin D metabolism, and a number of diseases associated with dysregulated Pi metabolism have been attributed to abnormal FGF23 signaling activities. The discovery of Klotho as a co-receptor for FGF23 signaling has also accelerated understanding on the molecular mechanisms underlying Pi and vitamin D metabolism...
October 1, 2016: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/26900884/phosphate-and-fgf23-in-the-renoprotective-benefit-of-raas-inhibition
#19
REVIEW
Sophie de Seigneux, Pierre-Yves Martin
Renin angiotensin-aldosterone system (RAAS) blockade is a mainstay of chronic kidney disease (CKD) treatment given its beneficial effects on proteinuria, nephroprotection, heart disease and global mortality. The FGF23/Klotho/phosphate axis is crucial for phosphate excretion. During CKD, loss of Klotho, decreased phosphate excretion and FGF23 elevation are early events contributing both to renal disease progression and to cardiovascular complications. Experimental evidence suggests that Klotho replacement may improve renal and cardiovascular disease during CKD...
April 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26827953/1-25-dihydroxyvitamin-d-and-klotho-a-tale-of-two-renal-hormones-coming-of-age
#20
Mark R Haussler, G Kerr Whitfield, Carol A Haussler, Marya S Sabir, Zainab Khan, Ruby Sandoval, Peter W Jurutka
1,25-Dihydroxyvitamin D3 (1,25D) is the renal metabolite of vitamin D that signals through binding to the nuclear vitamin D receptor (VDR). The ligand-receptor complex transcriptionally regulates genes encoding factors stimulating calcium and phosphate absorption plus bone remodeling, maintaining a skeleton with reduced risk of age-related osteoporotic fractures. 1,25D/VDR signaling exerts feedback control of Ca/PO4 via regulation of FGF23, klotho, and CYP24A1 to prevent age-related, ectopic calcification, fibrosis, and associated pathologies...
2016: Vitamins and Hormones
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