A5026404969- Parathyroid Disorders and Treatments
- Magnesium in Health and Disease
- Genetic Syndromes and Imprinting
- Fibroblast Growth Factor Research
- Biomedical Research and Pathophysiology
- Bone health and treatments
- Vitamin D Research Studies
- Muscle and Compartmental Disorders
- Folate and B Vitamins Research
- Kidney Stones and Urolithiasis Treatments
- Alkaline Phosphatase Research Studies
- Pancreatitis Pathology and Treatment
- Medical Imaging and Pathology Studies
- Cancer, Hypoxia, and Metabolism
- Hemoglobinopathies and Related Disorders
- Pediatric Urology and Nephrology Studies
- Electrolyte and hormonal disorders
- Connective tissue disorders research
- Soft tissue tumor case studies
- Heterotopic Ossification and Related Conditions
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Thyroid Disorders and Treatments
- Epigenetics and DNA Methylation
- Chronic Kidney Disease and Diabetes
- Cystic Fibrosis Research Advances
University of California, San Francisco
2015-2025
UCSF Benioff Children's Hospital
2019
Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which FGF-23 itself regulated are unknown. To determine whether serum concentration dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a(-/-)), Hyp mice diets containing varying Pi contents (0.02-1.65%). In WT mice, increases in from 0.02-1.65% induced 7-fold increase 3-fold concentrations. Across range concentrations varied...
Fibroblast growth factor-23 (FGF-23) is critical to the pathogenesis of a distinct group renal phosphate wasting disorders: tumor-induced osteomalacia, X-linked hypophosphatemia, and autosomal dominant recessive hypophosphatemic rickets. Excess circulating FGF-23 responsible for their major phenotypic features which include hypophosphatemia due inappropriately low serum 1,25(OH)2D concentrations. To characterize effects on sodium-phosphate (Na/P(i)) cotransport vitamin D metabolism, we...
In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the PHEX gene cause excess circulating levels of fibroblast growth factor 23 (FGF23), leading to lifelong renal phosphate wasting and hypophosphatemia. Adults with XLH present chronic musculoskeletal pain stiffness, short stature, lower limb deformities, fractures, pseudofractures due osteomalacia, accelerated osteoarthritis, dental abscesses, enthesopathy. Burosumab, a fully human monoclonal antibody, binds inhibits...
Burosumab, a fully human monoclonal antibody to FGF23, is the only approved treatment for X-linked hypophosphatemia (XLH), rare genetic disorder characterized by renal phosphate wasting and substantial cumulative musculoskeletal morbidity. During an initial 24-week randomized, controlled trial, 134 adults with XLH received burosumab 1 mg/kg (n = 68) or placebo 66) every 4 weeks. After 24 weeks, all subjects open-label until week 48. This report describes efficacy safety of during period....
Vitamin D 1alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1, is an autosomal recessive disorder characterized by the early onset of with hypocalcemia and caused mutations 25-hydroxyvitamin (1alpha-hydroxylase, CYP27B1) gene. The human gene encoding 5 kb in length, located on chromosome 12, comprises nine exons eight introns. We previously isolated cDNA identified 19 different 25 patients deficiency. OBJECTIVES, PATIENTS, AND METHODS: analyzed 10 patients, five...
The mitochondrial enzyme 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by the CYP27B1 gene, converts 25OHD to biological active form of vitamin D, 1,25-dihydroxyvitamin (1,25(OH)2D). Renal 1α-hydroxylase activity principal determinant circulating 1,25(OH)2D concentration and tightly regulated several factors. Fibroblast growth factor-23 (FGF-23) decreases serum concentrations suppressing mRNA abundance in mice. In extra-renal tissues, responsible for local synthesis, has important...
Background and objectives Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD children. High FGF23 levels associate with progression adults. Whether predicts children is unknown. Design, setting, participants, & measurements We tested hypothesis that high plasma an independent risk for 419 children, aged 1–16 years, enrolled Chronic Kidney Disease Children (CKiD) cohort study. measured at baseline determined GFR annually using disappearance...
Objectives To report the impact of burosumab on patient-reported outcomes (PROs) and ambulatory function in adults with X-linked hypophosphataemia (XLH) through 96 weeks. Methods Adults diagnosed XLH were randomised 1:1 a double-blinded trial to receive subcutaneous 1 mg/kg or placebo every 4 weeks for 24 ( NCT02526160 ). Thereafter, all subjects received until week 96. PROs measured using Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory-Short Form...
Abstract In X-linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF-23) are critical to pathogenesis disordered metabolism phosphate (Pi) 1,25-dihydroxyvitamin D [1,25(OH)2D]. this study, we hypothesized that mice, FGF-23-mediated suppression renal 1,25(OH)2D production Pi reabsorption depends on activation mitogen-activated protein kinase (MAPK) signaling. Wild-type mice were administered either...
Abstract Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and versus continuing oral phosphate active vitamin D (conventional therapy) in randomized, open-label, phase 3 trial involving children aged 1–12 years with X-linked hypophosphatemia. Patients were randomized (1:1) subcutaneous burosumab or continue conventional therapy. We present patient-reported...
The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)2D] production, rachitic bone disease. Increased serum fibroblast growth factor-23 concentration responsible for disordered metabolism of Pi 1,25(OH)2D. In present study, we tested hypothesis that chronic inhibition factor-23-induced activation MAPK signaling Hyp...
Abstract Context In an open-label, randomized, controlled, phase 3 trial in 61 children aged 1 to 12 years with X-linked hypophosphatemia (XLH), burosumab improved rickets vs continuing conventional therapy active vitamin D and phosphate. Objective We conducted analysis determine whether skeletal responses differed when switching higher or lower doses of therapy. Methods Conventional dose groups were defined as higher-dose phosphate [greater than 40 mg/kg] (HPi), lower-dose [40 mg/kg less]...
Abstract In a randomized, open-label phase 3 study of 61 children aged 1–12 years old with X-linked hypophosphatemia (XLH) previously treated conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 improved the phosphate metabolism, radiographic rickets, and growth compared therapy. this extension period (weeks 64–88), 21 continued Q2W at previous dose or crossed over from therapy starting 0.8 mg/kg clinical assessments through week 88. Efficacy endpoints safety observations...
Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency or resistance intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe the first identified case autoimmune hyperphosphatemic 8-year-old boy. In addition classical clinical...
Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and vitamin D metabolism. In patients with acute kidney injury (AKI), FGF23 levels rise rapidly after onset of AKI are associated progression increased mortality. mouse models AKI, excessive in is accompanied by a moderate increase expression bone. We examined the folic acid-induced (FA-AKI) model to determine whether other organs contribute plasma assessed axis as possible trigger for Fgf23 gene expression. Twenty-four...
Background: Genome-wide association studies (GWAS) have identified numerous genetic loci associated with mineral metabolism markers but exclusively focused on single-trait analysis. In this study, we performed a multi-trait analysis of GWAS (MTAG) metabolism, exploring overlapping architecture between traits to identify novel associations for fibroblast growth factor 23 (FGF23). Methods: We applied MTAG variants common 5 genetically correlated in European-ancestry participants. integrated UK...
Elevated fibroblast growth factor-23 (FGF23) has been consistently associated with heart failure, particularly failure preserved ejection fraction, among patients CKD and in the general population. FGF23 may directly induce cardiac remodeling failure. However, biases affecting observational studies impede robust causal inferences. Mendelian randomization leverages genetic determinants of a risk factor to examine causality. We performed two-sample assess associations between failure.Genetic...
Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphate (Pi) and vitamin D homeostasis. The transcription factor, early response 1 (egr-1), biomarker for FGF23-induced activation the ERK1/2 signaling pathway. We have shown that blockade suppresses renal egr-1 gene expression prevents hypophosphatemia 1,25-dihydroxyvitamin (1,25(OH)2D) suppression in mice. To test whether itself mediates these actions FGF23, we administered FGF23 to egr-1-/- wild-type (WT) In WT mice, induced...