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https://www.readbyqxmd.com/read/28339837/vitamin-d-treatment-attenuates-cardiac-fgf23-fgfr4-signaling-and-hypertrophy-in-uremic-rats
#1
Maren Leifheit-Nestler, Alexander Grabner, Laura Hermann, Beatrice Richter, Karin Schmitz, Dagmar-Christiane Fischer, Christopher Yanucil, Christian Faul, Dieter Haffner
Background.: Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. Methods...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28336829/-the-effect-of-oral-calcimimetics-on-cardiovascular-events
#2
Takayuki Hamano
The Evolve Trial showed no significant benefit of cinacalcet on the primary composite outcome(death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event)but significantly reduced the incidence of heart failure in an intention-to-treat(ITT)analysis. In an adjusted ITT analysis and lag-censoring analysis, the effect of cinacalcet on the primary outcome was significant. The reduced incidence of cardiovascular events in the cinacalcet arm could by predicted by a >=30% reduction in FGF23 levels at week 20...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28326356/effect-of-four-monthly-doses-of-a-human-monoclonal-anti-fgf23-antibody-krn23-on-quality-of-life-in-x-linked-hypophosphatemia
#3
Mary D Ruppe, Xiaoping Zhang, Erik A Imel, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, Thomas O Carpenter
X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE: Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28324013/acute-parathyroid-hormone-injection-increases-c-terminal-but-not-intact-fibroblast-growth-factor-23-levels
#4
V M Knab, B Corbin, O Andrukhova, J M Hum, P Ni, S Rabadi, A Maeda, K E White, R G Erben, H Jüppner, M Christov
The acute effects of PTH on FGF23 in vivo are not well understood. After a single s.c. PTH(1-34) injection (50nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/C-terminal FGF23 (cFGF23). Furthermore, FGF23 mRNA and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by 3-5-fold within two hours following PTH injection, which returned to baseline by 4 hours...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323996/molecular-physiology-of-the-hypocalcemic-action-of-fibroblast-growth-factor-23-in-zebrafish-danio-rerio
#5
Chia-Hao Lin, Huei-Jyun Hu, Pung-Pung Hwang
Fibroblast growth factor 23 (FGF23), a hormone required for phosphorus metabolism, was recently proposed to act on Ca2+ uptake; however, the available evidences of how FGF23 controls the body fluid Ca2+ homeostasis needs to be further clarified. The use of zebrafish as a model system revealed that FGF23 is specifically expressed in the corpuscles of Stannius (CS), an organ involved in Ca2+ homeostasis in fish, and its expression is stimulated by ambient water with a high Ca2+ level. The overexpression of FGF23 inhibited Ca2+ uptake by downregulating the mRNA expression of epithelium calcium channel (ECaC)...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323987/fibroblast-growth-factor-23-mineral-metabolism-and-adiposity-in-normal-kidney-function
#6
Sarah Zaheer, Ian H de Boer, Matthew Allison, Jenifer M Brown, Bruce M Psaty, Cassianne Robinson-Cohen, Erin D Michos, Joachim H Ix, Bryan Kestenbaum, David Siscovick, Anand Vaidya
Context: Obesity is associated with poor bone mineralization and quality. Fibroblast growth factor 23 (FGF23) plays an important role in calcium, phosphate, and skeletal physiology. Objective: To test the hypothesis that greater adiposity results in higher FGF23 levels among individuals with normal estimated glomerular filtration rate (eGFR). Design, Setting, Participants: Cross-sectional analyses among participants of the Multi-Ethnic Study of Atherosclerosis with eGFR ≥60 mL/min/1...
January 17, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323960/fgf23-is-not-associated-with-age-related-changes-in-phosphate-but-enhances-renal-calcium-reabsorption-in-girls
#7
Deborah M Mitchell, Harald Jüppner, Sherri-Ann M Burnett-Bowie
Context: Fibroblast growth factor 23 (FGF23) is a critical determinant of phosphate homeostasis. The role of FGF23, however, in regulating physiologic changes in serum phosphate and renal phosphate handling across childhood is not well-described. In addition, animal models have suggested a role for FGF23 in regulating renal calcium excretion. Objective: To assess changes in FGF23 concentrations across childhood in relation to changes in mineral ions and hormones of mineral ion homeostasis...
January 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323064/the-relevance-of-%C3%AE-klotho-to-the-central-nervous-system-some-key-questions
#8
REVIEW
Marina Minto Lopes-Cararo, Caio Henrique Yokoyama Mazucanti, Cristoforo Scavone, Elisa Mitiko Kawamoto, Daniel Charles Berwick
α-Klotho is well described as an anti-aging protein, with critical roles in kidney function as a transmembrane co-receptor for FGF23, and as a soluble factor in serum. α-Klotho is also expressed in the choroid plexus, where it is released into the cerebrospinal fluid. Nonetheless, α-Klotho is also expressed in the brain parenchyma. Accumulating evidence indicates that this pool of α-Klotho, which we define as brain α-Klotho, may play important roles as a neuroprotective factor and in promoting myelination, thereby supporting healthy brain aging...
March 18, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28298360/stimulation-of-fibroblast-growth-factor-23-by-metabolic-acidosis-requires-osteoblastic-intracellular-calcium-signaling-and-prostaglandin-synthesis
#9
Nancy S Krieger, David A Bushinsky
Serum fibroblast growth factor 23 (FGF23) increases progressively in chronic kidney disease (CKD) and is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the factors regulating its production are not clear. Patients with CKD have decreased renal acid excretion leading to metabolic acidosis (MET). During MET, acid is buffered by bone with release of mineral calcium (Ca) and phosphate (P). MET increases intracellular Ca signaling and cyclooxygenase 2 (COX2)-induced prostaglandin production in the osteoblast leading to decreased bone formation and increased bone resorption...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28294047/klotho-fgf23-cardiovascular-disease-and-vascular-calcification-black-or-white
#10
Giuseppe Cianciolo, Andrea Galassi, Irene Capelli, Roberto Schillaci, Gaetano La Manna, Mario Cozzolino
Patients affected by Chronic Kidney Disease and Mineral Bone Disorder (CKD-MBD) have a high risk of cardiovascular (CV) mortality that is poorly explained by traditional risk factors. The newest medical treatments for CKD-MBD have been associated with encouraging, but still inconsistent, improvement in CV disease complications and patient survival. A better understanding of the biomarkers and mechanisms of left ventricular hypertrophy (LVH), atherosclerosis, and vascular calcification (VC) may help with diagnosis and treatment of the organ damage that occurs secondary to CKD-MBD, thus improving survival...
March 9, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28288230/-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...
February 2017: Revista Chilena de Pediatría
https://www.readbyqxmd.com/read/28273060/mc4r-dependent-suppression-of-appetite-by-bone-derived-lipocalin-2
#12
Ioanna Mosialou, Steven Shikhel, Jian-Min Liu, Antonio Maurizi, Na Luo, Zhenyan He, Yiru Huang, Haihong Zong, Richard A Friedman, Jonathan Barasch, Patricia Lanzano, Liyong Deng, Rudolph L Leibel, Mishaela Rubin, Thomas Nicholas, Wendy Chung, Lori M Zeltser, Kevin W Williams, Jeffrey E Pessin, Stavroula Kousteni
Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28257739/candidate-gene-analyses-of-3-dimensional-dentoalveolar-phenotypes-in-subjects-with-malocclusion
#13
Cole A Weaver, Steven F Miller, Clarissa S G da Fontoura, George L Wehby, Brad A Amendt, Nathan E Holton, Veeratrishul Allareddy, Thomas E Southard, Lina M Moreno Uribe
INTRODUCTION: Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes DUSP6,ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion...
March 2017: American Journal of Orthodontics and Dentofacial Orthopedics
https://www.readbyqxmd.com/read/28250301/tumor-induced-osteomalacia-caused-by-a-parotid-tumor
#14
Yuichi Takashi, Yuka Kinoshita, Nobuaki Ito, Manabu Taguchi, Masaaki Takahashi, Naoya Egami, Shogo Tajima, Masaomi Nangaku, Seiji Fukumoto
A 77-year-old man was suspected of having tumor-induced osteomalacia (TIO) because of hypophosphatemia (1.9 mg/dL) and elevated serum fibroblast growth factor 23 (FGF23) level (186.9 pg/mL). We detected a tumor in his left parotid gland, and the FGF23 level in the left external jugular vein indicated that the tumor overproduced FGF23. After the removal of the tumor, the serum FGF23 level rapidly decreased, and the serum phosphate normalized. This is the first case of TIO caused by a tumor in a parotid gland...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28237867/exploratory-analysis-of-biomarkers-associated-with-clinical-outcomes-from-the-study-of-lenvatinib-in-differentiated-cancer-of-the-thyroid
#15
Makoto Tahara, Martin Schlumberger, Rossella Elisei, Mouhammed Amir Habra, Naomi Kiyota, Ralf Paschke, Corina E Dutcus, Taro Hihara, Shannon McGrath, Mark Matijevic, Tadashi Kadowaki, Yasuhiro Funahashi, Steven I Sherman
BACKGROUND: Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo in the phase III Study of (E7080) LEnvatinib in differentiated Cancer of the Thyroid (SELECT) of patients with radioiodine-refractory differentiated thyroid cancer. This exploratory analysis investigated potential predictive biomarkers of lenvatinib efficacy and target engagement. PATIENTS AND METHODS: Circulating cytokine/angiogenic factors (CAFs) in blood samples collected at baseline and throughout treatment were analysed from patients randomised to receive lenvatinib or placebo from August 5, 2011 to October 4, 2012...
February 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28212898/low-serum-iron-is-associated-with-high-serum-intact-fgf23-in-elderly-men-the-swedish-mros-study
#16
Catharina Lewerin, Östen Ljunggren, Herman Nilsson-Ehle, Magnus K Karlsson, Hans Herlitz, Mattias Lorentzon, Claes Ohlsson, Dan Mellström
BACKGROUND: Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. OBJECTIVE: To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men...
February 14, 2017: Bone
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
#17
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/28203361/long-term-iron-polymaltose-infusions-associated-with-hypophosphataemic-osteomalacia-a-report-of-two-cases-and-review-of-the-literature
#18
REVIEW
Ramy H Bishay, Kirtan Ganda, Markus J Seibel
Iron-induced hypophosphataemic osteomalacia remains under-recognized as a potential complication of parenteral iron therapy. We here report two cases of symptomatic hypophosphataemic osteomalacia with multiple insufficiency fractures in the context of chronic gastrointestinal blood loss, necessitating monthly iron polymaltose infusions over prolonged periods of time. Respective blood tests revealed severe hypophosphataemia [0.29 and 0.43; normal range (NR) 0.8-1.5 mmol/l] in the presence of normal serum calcium and 25-hydroxy vitamin D levels...
January 2017: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28193220/a-rare-case-of-multiple-phosphaturic-mesenchymal-tumors-along-a-tendon-sheath-inducing-osteomalacia
#19
Ryuta Arai, Tomohiro Onodera, Mohamad Alaa Terkawi, Tomoko Mitsuhashi, Eiji Kondo, Norimasa Iwasaki
BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, reduction of 1,25-dihydroxyl vitamin D, and bone calcification disorders. Tumors associated with TIO are typically phosphaturic mesenchymal tumors that are bone and soft tissue origin and often present as a solitary tumor. The high production of fibroblast growth factor 23 (FGF23) by the tumor is believed to be the causative factor responsible for the impaired renal tubular phosphate reabsorption, hypophosphatemia and osteomalacia...
February 13, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28191535/association-of-serum-intact-fibroblast-growth-factor-23-with-left-ventricular-mass-and-different-echocardiographic-findings-in-patients-on-hemodialysis
#20
Amir Ahmad Nassiri, Monir Sadat Hakemi, Reza Safar-Pour, Ali Ahmadi, Maryam Tohidi, Babak Sharif Kashani, Fatemeh Esfehani, Soudabeh Alatab
OBJECTIVES: To determine the association of fibroblast growth factor 23 (FGF23) with left ventricular hypertrophy (LVH) through the assessment of left ventricular (LV) mass and left ventricular mass index (LVMI) in patients on hemodialysis, this study was done. METHODS: All patients on hemodialysis who are older than 18 years and in whom hemodialysis vintage was at least 6 months were enrolled. All patients were on hemodialysis thrice a week for 4 h using low-flux dialysis filters, polysulfone membranes, reverse osmosis purified water, and bicarbonate-base hemodialysis solution...
September 1, 2016: Journal of Translational Internal Medicine
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