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https://www.readbyqxmd.com/read/28543687/effect-of-a-single-intravenous-zoledronic-acid-administration-on-biomarkers-of-acute-kidney-injury-aki-in-patients-with-osteoporosis-a-pilot-study
#1
C Cipriani, J Pepe, C Clementelli, R Manai, L Colangelo, V Fassino, L Nieddu, S Minisola
AIMS: The pilot study was designed to evaluate the early effect of intravenous (iv) zoledronic acid (ZA) on renal function. METHODS: Five mg iv ZA was administered to 23 patients with osteoporosis (17 women and 6 men, mean age 73±7 SD years). Urinary NGAL, KIM-1, and MCP-1, plasma (p) MCP-1 and serum (s) IL-18, serum calcium (sCa), Creatinine clearance (CrCl), parathyroid hormone (PTH), plasma C-terminal FGF23 (pFGF23), serum (s) Klotho, calcium excretion (CaEx) and renal threshold phosphate concentration/GFR (TmPO4/GFR) were assessed at baseline, 24 hours (h) and day (d) 30 after administration...
May 25, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28540270/fgf-23-klotho-and-vitamin-d-levels-in-scleroderma
#2
Ravan Ahmadi, Mehrzad Hajialilo, Amir Ghorbanihaghjo, Ali Mota, Sina Raeisi, Nasrin Bargahi, Mohammad Valilo, Farahnaz Askarian
BACKGROUND: Scleroderma is a chronic connective tissue disease of unknown etiology. Vitamin D and parathyroid hormone (PTH) that play particular functions in calcium and phosphate homeostasis may be involved in the etiology of this disorder. Klotho, the co-receptor of the fibroblast growth factor 23 (FGF-23), can interfere with calcium and phosphate metabolism. The purpose of this study was to evaluate serum Klotho, FGF-23, intact PTH (iPTH) and vitamin D levels in scleroderma patients compared with the healthy controls...
April 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/28539162/longevity-klotho-gene-polymorphism-and-the-risk-of-dementia-in-older-men
#3
Osvaldo P Almeida, Bharti Morar, Graeme J Hankey, Bu B Yeap, Jonathan Golledge, Assen Jablensky, Leon Flicker
INTRODUCTION: Klotho variants (KL-VS) have been associated with increased longevity and better cognitive function. It is unclear whether they modulate dementia risk. METHODS: We recruited 527 men aged 71-87 years who were free of cognitive impairment. We used data linkage to track the onset of dementia over 10 years. KL-VS genotyping (rs9536314 T/G) followed standard procedures. RESULTS: The annual rate of dementia was 17.2‰ (95%CI=14.0-21...
July 2017: Maturitas
https://www.readbyqxmd.com/read/28535521/fibroblast-growth-factor-23-mineral-metabolism-and-beyond
#4
Alexander Grabner, Sandro Mazzaferro, Giuseppe Cianciolo, Stefanie Krick, Irene Capelli, Silverio Rotondi, Claudio Ronco, Gaetano La Manna, Christian Faul
Patients affected by chronic kidney disease (CKD) exhibit a high risk of cardiovascular mortality that is poorly explained by traditional risk factors. There is a growing awareness about the role of derangement of mineral metabolism that is currently accepted as a trigger and sustainer of cardiovascular disease (CVD) in CKD patients. The synthetic definition of CKD mineral and bone disorder (CKD-MBD) split the concept that the indexes of mineral metabolism extend their effects beyond the bone until the vascular wall and metabolic milieu of CKD patients through complex pathways...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28515448/involvement-of-vascular-aldosterone-synthase-in-phosphate-induced-osteogenic-transformation-of-vascular-smooth-muscle-cells
#5
Ioana Alesutan, Jakob Voelkl, Martina Feger, Denise V Kratschmar, Tatsiana Castor, Sobuj Mia, Michael Sacherer, Robert Viereck, Oliver Borst, Christina Leibrock, Meinrad Gawaz, Makoto Kuro-O, Stefan Pilz, Andreas Tomaschitz, Alex Odermatt, Burkert Pieske, Carsten A Wagner, Florian Lang
Vascular calcification resulting from hyperphosphatemia is a major determinant of mortality in chronic kidney disease (CKD). Vascular calcification is driven by aldosterone-sensitive osteogenic transformation of vascular smooth muscle cells (VSMCs). We show that even in absence of exogenous aldosterone, silencing and pharmacological inhibition (spironolactone, eplerenone) of the mineralocorticoid receptor (MR) ameliorated phosphate-induced osteo-/chondrogenic transformation of primary human aortic smooth muscle cells (HAoSMCs)...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515153/differential-regulation-of-renal-klotho-and-fgfr1-in-normal-and-uremic-rats
#6
Juan R Muñoz-Castañeda, Carmen Herencia, Maria Victoria Pendón-Ruiz de Mier, Maria Encarnación Rodriguez-Ortiz, Juan M Diaz-Tocados, Noemi Vergara, Julio M Martínez-Moreno, Maria Dolores Salmerón, William G Richards, Arnold Felsenfeld, Makoto Kuro-O, Yolanda Almadén, Mariano Rodríguez
In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28509123/serum-calcitriol-levels-in-a-patient-with-x-linked-hypophosphatemia-complicated-by-autosomal-dominant-polycystic-kidney-disease
#7
Satomi Kajita, Takehisa Yamamoto, Naoko Tsugawa, Hirohumi Nakayama, Takuo Kubota, Toshimi Michigami, Keiichi Ozono
Serum calcitriol [1,25(OH)2D] levels are low normal in the presence of hypophosphatemia in X-linked dominant hypophosphatemic rickets (XLH) due to elevated serum fibroblast growth factor 23 (FGF23) levels. We report a peculiar finding of markedly elevated serum 1,25(OH)2D levels in a patient with XLH complicated by autosomal dominant polycystic kidney disease (ADPKD) and retinitis pigmentosa (RP). She was diagnosed with XLH, ADPKD and RP at the age of 5, 13 and 15 years, respectively. After the diagnosis of ADPKD, the 1,25(OH)2D levels increased up to 282 pg/mL treated with a pharmacological dose of 1αOHD3 (1αOHD3)...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28508612/the-longevity-hormone-klotho-is-a-new-player-in-the-interacion-of-the-growth-hormone-insulin-like-growth-factor-1-axis
#8
Tami Rubinek, Ido Wolf, Dalit Modan-Moses
Klotho was first discovered as an aging-suppressor gene. Mice that do not express klotho die prematurely with multiple symptoms of aging, several of which are also characteristic of decreased GH/IGF-1 axis activity. Klotho is highly expressed in the brain, the kidney, and parathyroid and pituitary glands, but can also serve as a circulating hormone by its shedding, forming soluble klotho (sKlotho) that can be detected in blood, cerebrospinal fluid and urine. Several lines of evidence suggest an association between klotho levels and activity of the GH/IHG-1 axis: The GH-secreting cells in the anterior pituitary of klotho-deficient mice are hypotrophic; klotho levels are altered in subjects with pathologies of the GH/IGF-1 axis; and accumulating data indicate that klotho is a direct regulator of GH secretion...
September 2016: Pediatric Endocrinology Reviews: PER
https://www.readbyqxmd.com/read/28501532/targeted-inhibition-of-klotho-binding-to-fibroblast-growth-factor-23-prevents-hypophosphetemia
#9
Muhammad Fakhar, Sajid Rashid
Klotho is a transmembrane protein which plays significant role in the pathogenesis of phosphate ion (Pi)-related disorders. Pi accumulation in human kidney tissues results in the major metabolic disorders due to malfunctioning of Klotho-FGFR1-FGF23 trimeric complex. The potential role of Klotho in Pi metabolism was elaborated through modeling and interaction analysis of glycosyl hydrolase (GS1 and GS2) domains with Fibroblast growth factor 23 (FGF23). In order to inhibit the association of Klotho and FGF23, binding patterns of three reported hits (N-(2-chlorophenyl)-1H-indole-3-carboxamide, N-[2-(1-cyclohexen-1-yl)ethyl]-6,7,8,9-tetrahydropyrido[1,2-e]purin-4-amine and 2-(1-propyl)amino-11-chlorothiazolo[5,4-a]acridine) were evaluated through molecular docking analysis...
April 27, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28489248/intact-fgf23-and-%C3%AE-klotho-during-acute-inflammation-sepsis-in-ckd-patients
#10
Evangelia Dounousi, Claudia Torino, Patrizia Pizzini, Sebastiano Cutrupi, Vincenzo Panuccio, Graziella D'Arrigo, Samar Abd ElHafeez, Giovanni Tripepi, Francesca Mallamaci, Carmine Zoccali
No abstract text is available yet for this article.
May 10, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28472473/fgf21-is-required-for-cardiac-remodeling-in-pregnancy
#11
I Redondo-Angulo, A Mas-Stachurska, M Sitges, F J Tinahones, M Giralt, F Villarroya, A Planavila
Aims—: Fibroblast growth factor-21 (Fgf21) is an endocrine factor that contributes to many physiological and pathological processes, mainly via its action as a metabolic regulator. Recent studies have shown that Fgf21 plays an important role in cardiac tissue. Pregnancy offers a physiological model of adaptive and reversible heart enlargement, but the molecular mechanisms underlying this cardiac hypertrophy are poorly understood. Therefore, the aim was to analyze the role of Fgf21 during late pregnancy, and assess the physiological relevance of Fgf21 for cardiac tissue during this process...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28463984/%C3%AE-klotho-expression-determines-nitric-oxide-synthesis-in-response-to-fgf-23-in-human-aortic-endothelial-cells
#12
Chih-Ping Chung, Yu-Chun Chang, Yan Ding, Kenneth Lim, Qinghua Liu, Langjing Zhu, Wei Zhang, Tzong-Shi Lu, Guerman Molostvov, Daniel Zehnder, Li-Li Hsiao
Endothelial cells (ECs) express fibroblast growth factor (FGF) receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot...
2017: PloS One
https://www.readbyqxmd.com/read/28442546/modeled-structural-basis-for-the-recognition-of-%C3%AE-2-3-sialyllactose-by-soluble-klotho
#13
Jon D Wright, Sung-Wan An, Jian Xie, Joonho Yoon, Nicole Nischan, Jennifer J Kohler, Noelynn Oliver, Carmay Lim, Chou-Long Huang
Soluble Klotho (sKlotho) is the shed ectodomain of antiaging membrane Klotho that contains 2 extracellular domains KL1 and KL2, each of which shares sequence homology to glycosyl hydrolases. sKlotho elicits pleiotropic cellular responses with a poorly understood mechanism of actions. Notably, in injury settings, sKlotho confers cardiac and renal protection by down-regulating calcium-permeable transient receptor potential canonical type isoform 6 (TRPC6) channels in cardiomyocytes and glomerular podocytes. Inhibition of PI3K-dependent exocytosis of TRPC6 is thought to be the underlying mechanism, and recent studies showed that sKlotho interacts with α2-3-sialyllactose-containing gangliosides enriched in lipid rafts to inhibit raft-dependent PI3K signaling...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28431289/klotho-apoe%C3%AE%C2%B54-cognitive-ability-brain-size-atrophy-and-survival-a-study-in-the-aberdeen-birth-cohort-of-1936
#14
Clarisse F de Vries, Roger T Staff, Sarah E Harris, Dorota Chapko, Daniel S Williams, Polina Reichert, Trevor Ahearn, Christopher J McNeil, Lawrence J Whalley, Alison D Murray
A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition, and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show that, relative to noncarriers, KL-VS heterozygotes had (1) shorter survival; (2) smaller white matter volumes; (3) slower cognitive decline; and (4) greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected...
March 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28429560/is-there-a-role-for-newer-biomarkers-in-chronic-kidney-disease-mineral-and-bone-disorder-management
#15
Sven-Jean Tan, Michael Mx Cai
The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28428174/klotho-an-anti-aging-molecule-attenuates-oxidant-induced-alveolar-epithelial-cell-mtdna-damage-and-apoptosis
#16
Seok-Jo Kim, Paul Cheresh, Mesut Eren, Renea P Jablonski, Anjana Yeldandi, Karen M Ridge, Gr Scott Budinger, Dong-Hyun Kim, Myles S Wolf, Douglas Vaughan, David W Kamp
Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from 'exaggerated' lung aging and mitochondrial dysfunction are critical determinants promoting lung fibrosis. α-Klotho, which is an anti-aging molecule that is expressed predominantly in the kidney and secreted in the blood, can protect lung epithelial cells against hyperoxia-induced apoptosis. We reasoned that Klotho protects AEC exposed to oxidative stress in part by maintaining mitochondrial DNA (mtDNA) integrity and mitigating apoptosis...
April 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#17
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28416226/klotho-restoration-via-acetylation-of-peroxisome-proliferation-activated-receptor-%C3%AE-reduces-the-progression-of-chronic-kidney-disease
#18
Wenjun Lin, Qin Zhang, Lin Liu, Shasha Yin, Zhihong Liu, Wangsen Cao
Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho (1) expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation-Activated Receptor γ (PPARγ), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARγ acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28415155/letter-to-the-editor-regarding-dounousi-e-et%C3%A2-al-intact-fgf23-and-%C3%AE-klotho-during-acute-inflammation-sepsis-in-ckd-patients-eur-j-clin-invest-2016-46-234-41
#19
Axel Schlitt, Urban Sester, Martina Sester, Sarah Seiler-Mussler, Vincent Brandenburg, Elke Schäffner, Gunnar H Heine
With interest we read the recent European Journal of Clinical Investigation paper entitled "Intact FGF23 and α-Klotho during acute inflammation/sepsis in CKD patients" by E. Dounousi and coworkers (1). In their article, the authors analyse the association between acute infection and plasma levels of the phosphaturic hormone fibroblast growth factor 23 (FGF-23). The physiological regulation of FGF-23 is not fully understood so far, and hence novel pathophysiological data are of importance. Particularly the link between FGF23 and inflammation is a growing field...
April 17, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28411025/klotho-down-regulates-egr-1-by-inhibiting-tgf-%C3%AE-1-smad3-signaling-in-high-glucose-treated-human-mesangial-cells
#20
Yang Li, Fang Hu, Meng Xue, Yi-Jie Jia, Zong-Ji Zheng, Ling Wang, Mei-Ping Guan, Yao-Ming Xue
Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-β1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-β1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in DKD is unclear...
April 12, 2017: Biochemical and Biophysical Research Communications
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