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https://www.readbyqxmd.com/read/29791829/burosumab-therapy-in-children-with-x-linked-hypophosphatemia
#1
Thomas O Carpenter, Michael P Whyte, Erik A Imel, Annemieke M Boot, Wolfgang Högler, Agnès Linglart, Raja Padidela, William Van't Hoff, Meng Mao, Chao-Yin Chen, Alison Skrinar, Emil Kakkis, Javier San Martin, Anthony A Portale
BACKGROUND: X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. METHODS: In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range...
May 24, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29786640/vitamin-d-in-vascular-calcification-a-double-edged-sword
#2
REVIEW
Jeffrey Wang, Jimmy J Zhou, Graham R Robertson, Vincent W Lee
Vascular calcification (VC) as a manifestation of perturbed mineral balance, is associated with aging, diabetes and kidney dysfunction, as well as poorer patient outcomes. Due to the current limited understanding of the pathophysiology of vascular calcification, the development of effective preventative and therapeutic strategies remains a significant clinical challenge. Recent evidence suggests that traditional risk factors for cardiovascular disease, such as left ventricular hypertrophy and dyslipidaemia, fail to account for clinical observations of vascular calcification...
May 22, 2018: Nutrients
https://www.readbyqxmd.com/read/29777507/rankl-expression-is-increased-in-circulating-mononuclear-cells-of-patients-with-calcific-aortic-stenosis
#3
Marcello Rattazzi, Elisabetta Faggin, Elisa Bertacco, Roberta Buso, Massimo Puato, Mario Plebani, Martina Zaninotto, Davide Condotta, Giacomo Zoppellaro, Leopoldo Pagliani, Giuseppe Tarantini, Sabino Iliceto, Elisa Covolo, Giuseppe Faggian, Francesco Onorati, Mikhail Dodonov, Alessandro Daniotti, Paola Pantano, Zoran Olivari, Giovanni Benfari, Paolo Pauletto
We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0...
May 17, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29770125/fgf23-actions-on-target-tissues-with-and-without-klotho
#4
REVIEW
Beatrice Richter, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29764921/fibroblast-growth-factor-23-and-risks-of-cardiovascular-and-noncardiovascular-diseases-a-meta-analysis
#5
Amarnath Marthi, Killian Donovan, Richard Haynes, David C Wheeler, Colin Baigent, Christopher M Rooney, Martin J Landray, Sharon M Moe, Jun Yang, Lisa Holland, Romina di Giuseppe, Annet Bouma-de Krijger, Borislava Mihaylova, William G Herrington
Background Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43-74 RU/ml and 38-47 pg/ml in 17 general population cohorts; 102-392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79-4212 RU/ml and 2526-5555 pg/ml in eight cohorts of patients on dialysis...
May 15, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29748308/fibroblast-growth-factor-23-and-klotho-contribute-to-airway-inflammation
#6
Stefanie Krick, Alexander Grabner, Nathalie Baumlin, Christopher Yanucil, Scott Helton, Astrid Grosche, Juliette Sailland, Patrick Geraghty, Liliana Viera, Derek W Russell, J Michael Wells, Xin Xu, Amit Gaggar, Jarrod Barnes, Gwendalyn D King, Michael Campos, Christian Faul, Matthias Salathe
Circulating levels of fibroblast growth factor (FGF) 23 are associated with systemic inflammation and increased mortality in chronic kidney disease. α-klotho, a co-receptor for FGF23, is downregulated in chronic obstructive pulmonary disease (COPD). However, whether FGF23 and klotho-mediated FGFR activation delineates a pathophysiologic mechanism in COPD remains unclear. We hypothesized that FGF23 can potentiate airway inflammation via klotho independent FGFR4 activation. FGF23 and its effect were studied using plasma and transbronchial biopsies from COPD and control patients and primary human bronchial epithelial cells isolated from COPD patients as well as a murine COPD model...
May 10, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29726397/under-recognized-hypoparathyroidism-in-thalassemia
#7
Hataitip Tangngam, Pat Mahachoklertwattana, Preamrudee Poomthavorn, Ampaiwan Chuansumrit, Nongnuch Sirachainan, La-or Chailurkit, Patcharin Khlairit
OBJECTIVE: Symptomatic hypoparathyroidism [symptomatic hypocalcemia without elevated serum parathyroid hormone (PTH)] in patients with thalassemia is relatively rare. Asymptomatic mild hypocalcemia without elevated PTH which is considered hypoparathyroidism may be more common but under-recognized. METHODS: Sixty-six transfusion-dependent thalassemic patients, and 28 healthy controls were enrolled. Serum calcium (Ca), phosphate (P), creatinine (Cr), albumin, intact PTH, 25-hydroxyvitamin D (25-OHD), plasma intact fibroblast growth factor-23 (FGF-23), urine Ca, P and Cr were measured...
May 4, 2018: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29710336/association-of-fibroblast-growth-factor-23-with-recurrent-cardiovascular-events-in-patients-after-an-acute-coronary-syndrome-a-secondary-analysis-of-a-randomized-clinical-trial
#8
Brian A Bergmark, Jacob A Udell, David A Morrow, Christopher P Cannon, Dylan L Steen, Petr Jarolim, Andrzej Budaj, Christian Hamm, Jianping Guo, KyungAh Im, Julia F Kuder, Eugene Braunwald, Marc S Sabatine, Michelle L O'Donoghue
Importance: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with myocardial fibrosis and renin-angiotensin system upregulation, potentially providing prognostic information distinct from standard cardiovascular (CV) biomarkers. Objective: To evaluate the association of FGF-23 with recurrent CV events in patients after an acute coronary syndrome (ACS). Design, Setting, and Participants: C-terminal FGF-23 was measured in plasma samples using an established enzyme-linked immunosorbent assay system for 4947 patients within 30 days of ACS (median, 14 days) and with 1 additional CV risk factor in the Stabilization of Plaques Using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) trial of the lipoprotein-associated phospholipase A2 inhibitor darapladib vs placebo performed from December 1, 2009, to April 24, 2014 (median follow-up, 2...
April 18, 2018: JAMA Cardiology
https://www.readbyqxmd.com/read/29708879/fibroblast-growth-factor-23-and-renal-function-among-young-and-healthy-individuals
#9
Raffaele Bernasconi, Stefanie Aeschbacher, Steffen Blum, Michel Mongiat, Marc Girod, John Todd, Joel Estis, Niamh Nolan, Harald Renz, Lorenz Risch, David Conen, Martin Risch
BACKGROUND: Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals. METHODS: Healthy individuals aged 25-41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate...
May 1, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29704936/associations-between-single-nucleotide-polymorphisms-in-the-calcium-sensing-receptor-and-chronic-kidney-disease-mineral-and-bone-disorder-in-cats
#10
R F Geddes, R E Jepson, Y Forcada, J Elliott, H M Syme
Feline chronic kidney disease (CKD) is associated with high variability in severity of CKD-mineral and bone disorder (CKD-MBD). The calcium sensing receptor (CaSR) regulates circulating parathyroid hormone (PTH) and calcium concentrations. Single nucleotide polymorphisms (SNPs) in the CaSR are associated with severity of secondary renal hyperparathyroidism and total calcium concentrations in human patients receiving haemodialysis. The objective of this study was to explore associations between polymorphisms in the feline CaSR (fCaSR) and biochemical changes observed in CKD-MBD...
May 2018: Veterinary Journal
https://www.readbyqxmd.com/read/29698460/growth-differentiation-factor-15-and-fibroblast-growth-factor-23-are-associated-with-mortality-in-type-2-diabetes-an-observational-follow-up-study
#11
Marie Frimodt-Møller, Bernt Johan von Scholten, Henrik Reinhard, Peter Karl Jacobsen, Tine Willum Hansen, Frederik Ivar Persson, Hans-Henrik Parving, Peter Rossing
OBJECTIVES: Two biomarkers, growth differentiation factor 15 (GDF-15) and fibroblast growth factor 23 (FGF-23)), reflecting different aspects of renal pathophysiology, were evaluated as determinants of decline in estimated glomerular filtration rate (eGFR), incident cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D) and microalbuminuria, but without clinical cardiac disease. MATERIALS AND METHODS: Prospective study including 200 T2D patients...
2018: PloS One
https://www.readbyqxmd.com/read/29672176/prevalence-and-risk-factors-for-vascular-calcification-in-chinese-patients-receiving-dialysis-baseline-results-from-a-prospective-cohort-study
#12
Zhi-Hong Liu, Xue-Qing Yu, Jun-Wei Yang, Ai-Li Jiang, Bi-Cheng Liu, Chang-Ying Xing, Ji-Zhuang Lou, Mei Wang, Hong Cheng, Jun Liu, Jun-Zhou Fu, Ai-Hua Zhang, Miao Zhang, Qiao-Ling Zhou, Chen Yu, Rong Wang, Li Wang, Yu-Qing Chen, Tian-Jun Guan, Ai Peng, Chen Nan, Chuan-Ming Hao, Xu-Yang Cheng
OBJECTIVE: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD). METHODS: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline...
April 19, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29671909/should-phosphate-management-be-limited-to-the-kdigo-kdoqi-guidelines
#13
Sangeet Dhillon-Jhattu, Stuart M Sprague
Hyperphosphatemia is a common complication of CKD. Prior to development of overt hyperphosphatemia, there are several adaptive mechanisms that occur to maintain normal phosphorus equilibrium in patients with CKD. These include an early and progressive rise in fibroblast growth factor 23 (FGF 23), followed by an increase in parathyroid hormone (PTH) with a decrease in 1,25-dihydroxyvitamin D (1,25 Vit D). Over the last 20 years, a large number of studies have shown that hyperphosphatemia is a strong predictor of adverse clinical outcomes including increased incidence of vascular calcification, cardiovascular disease, and all-cause mortality in both individuals with CKD as well as those with normal kidney function...
April 19, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29665846/correlation-of-serum-levels-of-fibroblast-growth-factor-23-and-klotho-protein-levels-with-bone-mineral-density-in-maintenance-hemodialysis-patients
#14
Shubei Zheng, Yan Chen, Yu Zheng, Zhihong Zhou, Zhanyuan Li
OBJECTIVE: The correlation of serum fibroblast growth factor 23 (FGF-23) and Klotho protein levels with bone mineral density (BMD) in maintenance hemodialysis (MHD) patients was analyzed. METHODS: Between January 2015 and November 2015, 125 MHD patients in our hospital were enrolled. Dual-energy X-ray absorptiometry was used to examine the BMD in the femoral neck and lumbar spine of MHD patients. The patients were divided into three groups: a normal bone mass group, an osteopenia group, and an osteoporosis group...
April 17, 2018: European Journal of Medical Research
https://www.readbyqxmd.com/read/29662617/premature-ovarian-aging-in-brca-carriers-a-prototype-of-systemic-precocious-aging
#15
Irit Ben-Aharon, Mattan Levi, David Margel, Rinat Yerushalmi, Shulamith Rizel, Shlomit Perry, Eran Sharon, Noa Hasky, Ronit Abir, Benny Fisch, Ana Tobar, Ruth Shalgi, Salomon Marcello Stemmer
Purpose: Though former evidence implies a correlation of breast cancer susceptibility gene ( BRCA ) mutation with reduced ovarian reserve, the data is yet inconsistent. Our aim was to investigate biomarkers of ovarian aging in a cohort of young healthy carriers of the BRCA mutation. We hypothesized that the role played by BRCA genes in aging pathways is not exclusive to the ovary. Experimental Design: Healthy female BRCA carriers, 40 years or younger and healthy male BRCA carriers, 50 years or younger, were enrolled in the study...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29660161/the-fgf-23-klotho-axis-and-its-relationship-with-phosphorus-calcium-vitamin-d-pth-aldosterone-severity-of-disease-and-outcome-in-hospitalised-foals
#16
A M Kamr, K A Dembek, B E Hildreth, P R Morresey, R A Rathgeber, T A Burns, A A Zaghawa, R E Toribio
BACKGROUND: Fibroblast growth factor-23 (FGF-23) and klotho are key regulators of vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and calcium homeostasis; however, information on the FGF-23/klotho axis in healthy and hospitalised foals is lacking. OBJECTIVES: The aims of this study were to measure serum FGF-23 and klotho concentrations and determine their association with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D, 1,25(OH)2 D], PTH, and aldosterone concentrations, disease severity, and mortality in hospitalised foals...
April 16, 2018: Equine Veterinary Journal
https://www.readbyqxmd.com/read/29621752/fibroblast-growth-factor-23-a-biomarker-of-kidney-function-decline
#17
David A Drew, Ronit Katz, Stephen Kritchevsky, Joachim H Ix, Michael G Shlipak, Anne B Newman, Andy Hoofnagle, Linda Fried, Mark J Sarnak, Orlando M Gutierrez
BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. METHODS: Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults...
2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29607318/calcitriol-prevents-cardiovascular-repercussions-in-puromycin-aminonucleoside-induced-nephrotic-syndrome
#18
Fernandes-Cerqueira Cátia, Quelhas-Santos Janete, Sampaio-Maia Benedita, Simões-Silva Liliana, Soares-Silva Isabel, Roncon-Albuquerque Roberto, Pestana Manuel
Puromycin aminonucleoside-induced nephrotic syndrome (PAN-NS) is characterized by cardiac remodeling and increased local inflammatory activity. Patients with NS and animal models of NS have vitamin D3 deficiency. The aim of the present study was to evaluate the influence of calcitriol on cardiac remodeling and local inflammatory state in PAN-NS rat model. Male Sprague-Dawley rats were injected with PAN or vehicle on day 0. PAN and control rats were divided into two subgroups for the administration of calcitriol (PAN-D and Ct-D groups) or the vehicle (PAN-V and Ct-V groups) during 21 days...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29606304/fibroblast-growth-factor-23-is-associated-with-adiposity-in-patients-receiving-hemodialysis-possible-cross-talk-between-bone-and-adipose-tissue
#19
Janet M Chiang, George A Kaysen, Anne L Schafer, Cynthia Delgado, Kirsten L Johansen
OBJECTIVE: Fibroblast growth factor 23 (FGF-23) may be involved in signaling between bone and adipose tissue in dialysis patients, but its role is uncertain. We sought to examine the association between FGF-23 and adiposity and whether this association is mediated in part by leptin. DESIGN/SETTING: We performed univariate and multivariate linear regression analyses using data from 611 participants in a cohort of prevalent hemodialysis patients recruited from dialysis centers in Atlanta, GA and San Francisco, CA from 2009 to 2011...
March 29, 2018: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/29599772/the-gut-microbiota-regulates-endocrine-vitamin-d-metabolism-through-fibroblast-growth-factor-23
#20
Stephanie A Bora, Mary J Kennett, Philip B Smith, Andrew D Patterson, Margherita T Cantorna
To determine the effect of the microbiota on vitamin D metabolism, serum 25-hydroxyvitamin D(25D), 24,25-dihydroxyvitamin D (24,25D), and 1,25-dihydroxyvitamin D (1,25D) were measured in germ-free (GF) mice before and after conventionalization (CN). GF mice had low levels of 25D, 24,25D, and 1,25D and were hypocalcemic. CN of the GF mice with microbiota, for 2 weeks recovered 25D, 24,25D, and 1,25D levels. Females had more 25D and 24,25D than males both as GF mice and after CN. Introducing a limited number of commensals (eight commensals) increased 25D and 24,25D to the same extent as CN...
2018: Frontiers in Immunology
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