A5021526213- Parathyroid Disorders and Treatments
- Vitamin D Research Studies
- Magnesium in Health and Disease
- Bone health and treatments
- Genetic Syndromes and Imprinting
- Electrolyte and hormonal disorders
- Muscle and Compartmental Disorders
- Renal Transplantation Outcomes and Treatments
- Medical Imaging and Pathology Studies
- Potassium and Related Disorders
- Digestive system and related health
- Biomedical Research and Pathophysiology
- Chronic Myeloid Leukemia Treatments
- Dialysis and Renal Disease Management
- Alkaline Phosphatase Research Studies
- Growth Hormone and Insulin-like Growth Factors
- Sexual Differentiation and Disorders
- Folate and B Vitamins Research
- Pancreatitis Pathology and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Ion Transport and Channel Regulation
- Diet and metabolism studies
- Fibroblast Growth Factor Research
- Birth, Development, and Health
- Childhood Cancer Survivors' Quality of Life
University of California, San Francisco
2016-2025
UCSF Benioff Children's Hospital
2018-2024
University of Groningen
2018-2021
University of San Francisco
2020
Birmingham Children's Hospital
2018
Royal Manchester Children's Hospital
2018
Great Ormond Street Hospital
2018
University of California System
2018
University College London
2018
Indiana University – Purdue University Indianapolis
2018
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 important in the regulation of phosphorus and vitamin D metabolism. States excess circulating FGF-23 are associated with renal phosphate wasting inappropriately low serum 1,25-dihydroxyvitamin [1,25(OH)(2)D] concentrations. Conversely, states absent or biologically inactive increased 1,25(OH)(2)D Restriction dietary intake increases reabsorption production, whereas opposite occurs when supplemented.We sought to determine whether concentration regulated...
X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to and consequently rickets, osteomalacia, skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with hypophosphatemia.
The secosteroid hormone, 1,25-dihydroxyvitamin D[ 1,25(OH)2D], plays a crucial role in normal bone growth, calcium metabolism, and tissue differentiation. key step the biosynthesis of 1,25-(OH)2D is its 1α-hydroxylation from 25-hydroxyvitamin D (25-OHD) kidney. Because expression kidney very low, we cloned sequenced cDNA for 25-OHD-1α-hydroxylase (P450c1α) human keratinocytes, which 1α-hydroxylase activity mRNA can be induced to much greater. P450c1α was expressed at lower levels kidney,...
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence SIADH, yet who had undetectable arginine vasopressin (AVP) levels. hypothesized that they gain-of-function mutations in V2 receptor (V2R). DNA sequencing each patient's V2R gene (AVPR2) identified missense both, resultant changes codon 137 from to cysteine or leucine. These novel constitutive...
The hyperparathyroidism characteristic of patients with moderate renal insufficiency could be caused by decreases in the plasma concentration ionized calcium (Ca++) evoked by: (a) recurring increases inorganic phosphorus that may detectable only post-prandial period; (b) a reversible, phosphorus-mediated suppression 25-hydroxyvitamin D-1 alpha-hydroxylase 1,25-dihydroxyvitamin D (1,25-(OH)2D) enough to decrease both gut absorption and bone resorption Ca++; (c) these. In group eight children...
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...
We asked this question: in normal humans, is either a dietary intake or serum concentration of phosphorus determinant the 1,25(OH)2D? In seven men whose was decreased from 2,300 to 625 mg/d, each for 8-9 d, under strictly controlled, metabolic conditions, we measured concentrations 1,25(OH)2D daily, and hourly throughout 24-h period, before after restriction. Decreasing induced: (a) 58% increase levels 1,25(OH)2D; (b) 35% decrease afternoon; (c) 12% mean level phosphorus; but, (d) no morning...
Changes in the oral intake of phosphorus could induce reported changes serum concentration 1,25-dihydroxyvitamin D (1,25-(OH)2D) by inducing its production rate (PR) or metabolic clearance (MCR), both. To investigate these possibilities, we employed constant infusion equilibrium technique to measure PR and MCR 1,25-(OH)2D six healthy men whom was initially maintained at 1,500 mg/70 kg body weight per d for 9 d, then restricted 500 mg/d (coupled with administration aluminum hydroxide) 10...
We recently reported that in healthy men, changes the production rate (PR) of 1,25-dihydroxyvitamin D [1,25-(OH)2D] accounted for 80% increase and 30% decrease its serum concentration was induced by restriction supplementation, respectively, dietary phosphorus. These PR 1,25-(OH)2D could be mediated concentrations phosphorus occur after morning fasting period. To examine this hypothesis, we measured blood drawn at hourly intervals 24 h six men whom initially maintained 1,500 mg/70 kg body...
In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the renal tubular maximum reabsorption rate of phosphate/glomerular filtration (TmP/GFR) and serum inorganic phosphorus (Pi), resulting in rickets and/or osteomalacia. The objective was to test hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve Pi adults with XLH. Two sequential open-label phase 1/2 studies were done. Six academic medical centers used. Twenty-eight XLH...
In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess 1,25-dihyroxyvitamin D deficiency across spectrum predialysis CKD. This study characterized circulating concentrations D, investigated their interrelationships associations GFR secondary hyperparathyroidism in CKD who were enrolled Chronic Kidney Disease Children observational cohort study.Plasma mineral metabolism measured 464 ages 1-16 years was by plasma...
To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed 12 transplant centers. One hundred thirty children receiving primary transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate standard dose daclizumab (SB group) extended (SF group). Follow-up 3 years posttransplant. Standardized height Z-score change after follow-up -0.99...
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....
Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk infection and other stresses, while reducing costs rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center subsequently validated cross-validated QPCR in NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total 367 unique human PB samples, each paired with for centralized, blinded phenotype...
Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, years 1, 3, and 5 through November 2009, annually thereafter. We used Cox regression analysis of first incident evaluate potential correlates risk. At enrollment, median age was 11 years, 16% patients reported a prior...
In adults with X-linked hypophosphatemia (XLH), excess FGF23 impairs renal phosphate reabsorption and suppresses production of 1,25-dihydroxyvitamin D, resulting in chronic persistent osteomalacia. Osteomalacia is associated poor bone quality causing atraumatic fractures, pseudofractures, delayed fracture healing, pain. Burosumab a fully human monoclonal antibody against FGF23. UX023-CL304 an ongoing, open-label, single-arm, phase 3 study investigating the efficacy subcutaneous burosumab,...
Abstract Purpose In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate active vitamin D, or monotherapy burosumab, a monoclonal antibody approved treat children adults XLH. We have previously reported outcomes up 64 weeks, here we report safety efficacy follow-up results 160 weeks from an open-label, multicenter, randomized,...
Abstract Context Younger age at treatment onset with conventional therapy (phosphate salts and active vitamin D; Pi/D) is associated improved growth skeletal outcomes in children X-linked hypophosphatemia (XLH). The effect of on burosumab efficacy safety XLH unknown. Objective This work aimed to explore the vs Pi/D younger (< 5 years) older (5-12 XLH. Methods post hoc analysis a 64-week, open-label, randomized controlled study took place 16 academic centers. Sixty-one aged 1 12 years...
Abstract Background An International Working Group (IWG) developed new guidelines on the diagnosis, evaluation, management, and monitoring of X-linked hypophosphatemia (XLH) in children. Over past 5 years, important advances have occurred our understanding presentation, complications treatment XLH. Methods A group 50 international experts XLH from Canada, United States, Europe, Asia South America, along with methodology patient partners, held 18 teleconference meetings 2023-2024. These...
Foscarnet (trisodium phosphonoformate), an investigational pyrophosphate analog increasingly used to treat refractory cytomegalovirus retinitis and mucocutaneous herpes simplex virus infections in immunocompromised patients, has been reported cause abnormalities serum calcium phosphate, including cases of fatal hypocalcemia. To further elucidate the magnitude mechanism these humans treated with foscarnet for opportunistic infections, we analyzed anaerobic specimens 24-h urine samples before...