Fibroblast Growth Factor 23 Research Articles

The Effect of Ferric Carboxymaltose on Fibroblast Growth Factor 23 (FGF23) in Children with Iron Deficiency Anemia Due to Gastrointestinal Diseases

Background: Hypophosphatemia is a known side-effect of parenteral iron administration, especially after intravenous ferric carboxymaltose (FCM). Fibroblast growth factor 23 (FGF23) is thought to play an important role in the pathophysiology of serum phosphate homeostasis. This study aimed to investigate the effects of FCM on FGF23 serum levels in FCM-treated pediatric patients with iron deficiency (ID)/iron deficiency anemia (IDA) caused by gastrointestinal diseases. Methods: Over 30 months, FGF23 serum levels were assessed prospectively in children with ID/IDA due to gastrointestinal diseases and treated with FCM infusion. Serum levels of intact FGF23 (iFGF23) were assessed and correlated to phosphate serum levels and factors of bone metabolism. Blood sampling was performed in three phases: before FCM infusion, 7–10 days after FCM infusion, and 6–8 weeks after FCM infusion. Results: A total of 42 FCM infusions were given to 35 children (20 girls) with a mean age (±SD) of 12.2 (±4.03) years (range: 2–16 years). The median levels of iFGF23 did not show a significant difference across the three phases (p = 0.56). No significant correlation was found between iFGF23 levels and 25-hydroxyvitamin D/parathyroid hormone/serum phosphate/serum calcium/alkaline phosphatase. No significant change was noted between pre- and post-treatment serum phosphate levels. However, four children (11.42%) developed asymptomatic and transient hypophosphatemia. Conclusions: No significant difference was found between pre-and post-FCM infusion serum iFGF23 levels and bone metabolism parameters. An increase of iFGF23 serum levels 7–10 days after FCM infusion was noted in patients with hypophosphatemia.

Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels.

Increased dietary inorganic phosphate (Pi) intake stimulates renal Pi excretion, in part, by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) or dopamine. High dietary Pi may also stimulate sympathetic outflow. Rodent studies provided evidence for these regulatory loops, while controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake. The effects of controlled, isolated changes in dietary Pi intake over shorter periods are unknown. We studied the effects of a low or high Pi diet on parameters of mineral metabolism in 10 healthy young men. Participants received a standardized diet (1000mg phosphorus equivalent/day) supplemented with either a phosphate binder (low Pi diet) or phosphate capsules (750mg phosphorus, high Pi diet) in a randomized cross-over trial for 5days with a 7-day washout between diets. High Pi intake increased plasma Pi levels and 24-h excretion and decreased urinary calcium excretion. High Pi intake increased intact FGF23 (iFGF23) and suppressed plasma Klotho without affecting cFGF23, PTH, calcidiol, calcitriol, Fetuin-A, dopamine, epinephrine, norepinephrine, metanephrine, or aldosterone. Higher iFGF23 correlated with lower calcitriol and higher PTH. These data support a role for iFGF23 in increasing renal Pi excretion and reducing calcitriol in healthy young men during steady-state high dietary Pi intake. High dietary Pi intake elevated blood Pi levels in healthy young subjects with normal renal function and may therefore be a health risk, as higher serum Pi levels are associated with cardiovascular risk in the general population.

Fibroblast growth factor 23 – A review with particular reference to the physiology and pathophysiology of phosphate homeostasis in the cat

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone, discovery of which has transformed our understanding of mineral regulation in healthy mammals, including the cat. It is produced by osteoblasts and osteocytes and its prime role is to regulate phosphate entry into extracellular fluid (from bone and via the gut) and its excretion via the kidney. It interacts with other hormones (calcitriol and parathyroid hormone), inhibiting their activation and secretion respectively and so impacts on calcium as well as phosphate homeostasis. Physiological factors regulating its secretion are not well understood, although phosphate ion sensing is likely to be important. Calcium and magnesium ions are also involved and unravelling the control points and integration of the system regulating bone turnover and mineral balance whilst preventing soft tissue (non-osseous) mineralisation is a future research goal. Calciprotein particle size and number likely play an important role in this system but precisely how remains to be determined. Elevated serum FGF23 is the earliest indicator of mineral bone disorder associated with chronic kidney disease in human patients and in cats, enabling reference-range serum phosphorus to be maintained despite reduction in glomerular filtration rate which limits phosphate excretion. FGF23 also predicts CKD progression and survival in cats. The many factors influencing its secretion at different stages of CKD, including relative iron deficiency, anaemia and chronic systemic inflammation, hypomagnesaemia and α-klotho deficiency are discussed in this review, where the data available in cats with naturally occurring CKD is presented alongside that from rodent models and human CKD patients.

Association of Fibroblast Growth Factor 23 and Cardiac Mechanics in the Cardiovascular Health Study.

Elevated levels of fibroblast growth factor 23 (FGF23) are associated with left ventricular hypertrophy and heart failure (HF) in individuals with and without kidney disease. Prior studies investigated the association of FGF23 and structural cardiac changes using conventional echocardiography, which is limited in its ability to detect early cardiac dysfunction. We investigated the relationship between FGF23 levels and cardiac dynamics using two-dimensional speckle tracking echocardiography (2D-STE), a novel imaging modality. This was a cross-sectional analysis of data from the Cardiovascular Health Study, an ongoing prospective, population-based cohort study. The study population included 506 participants from CHS with available c-terminal (cFGF23) and intact FGF23 (iFGF23) measurements from 1996-1997 and 2D-STE images from 1994-1995. Forty two percent of the study population had CKD, defined as an eGFR < 60 ml/min/1.73m2, and the mean eGFR was 63 ml/min/1.73m2. The primary exposures were cFGF23 and iFGF23. The primary outcomes were six 2D-STE parameters performed at the 1994-1995 study visit. Linear regression models were used to examine the independent associations of FGF23 with six cardiac 2D-STE indices adjusting for demographics, cardiovascular risk factors, markers of kidney disease severity, and inflammation. cFGF23 levels were moderately correlated with iFGF23 levels in the CHS population. In fully adjusted models, cFGF23 was associated with left atrial dysfunction, but no other cardiac imaging parameter (β estimate -2.47; 95% Confidence Interval -4.68, -0.25; Table 2). iFGF23 was not associated with any of the six 2D-STE indices. Limitations include small sample size and noncurrent FGF23 measurements and 2D-STE imaging. In a limited sample of individuals enrolled in the CHS with c- and i-FGF23 measurements, we did not find consistent associations between FGF23 levels and 2D-STE parameters. Further investigations in a larger population with concurrent 2D-STE are needed to better understand the associations of FGF23 with early changes in cardiac mechanics.

Acquired hypophosphatemic osteomalacia: case series from a Peruvian referral center (1999-2023).

Acquired hypophosphatemic osteomalacia (AHO) is a rare metabolic bone disorder characterized by hypophosphatemia and impaired bone mineralization. Tumor-induced osteomalacia (TIO) is the most common cause of AHO, caused by phosphaturic tumors that overproduce fibroblast growth factor 23 (FGF-23). To present the clinical characteristics, diagnostic challenges, and outcomes of seven cases of AHO in Peruvian patients between 1999 and 2023. A retrospective review of seven patients diagnosed with AHO was conducted. Clinical data, including diagnostic procedures, treatments, and outcomes, were collected. Seven cases of AHO were reviewed. In case one, osteomalacia did not improve despite supraphysiological doses of vitamin D (ergocalciferol/cholecalciferol), and no tumor was detected with available tests, resulting in the patient's death. Cases two and three involved tumors located in the right leg and right hemithorax, respectively, with symptom resolution following total resection. In cases four, five, and seven, exhaustive exams failed to locate tumors. Cases four, six, and seven showed elevated FGF-23 levels, while case five had inappropriately normal FGF-23 levels. Case seven was the first patient in Peru to receive burosumab treatment. In case six, a tumor in the head of the femur was identified, but the patient opted for nonsurgical management. The diagnosis of AHO is challenging, requiring a high index of clinical suspicion and biochemical confirmation. TIO is the most common cause of AHO, emphasizing the importance of locating the phosphaturic tumor. However, in some cases, the tumor remains elusive despite exhaustive diagnostic workups. This is particularly challenging in developing countries like Peru, where resources are limited.

Relationship of Serum Fibroblast Growth Factor 23, Hypoxia-Inducible Factor-1α, and Klotho with In-Stent Restenosis in Elderly Patients with Coronary Artery Disease after the Treatment of Percutaneous Coronary Intervention.

In-stent restenosis (ISR) commonly occurs in elderly patients with coronary artery disease (CAD) after percutaneous coronary intervention. Atherosclerosis in elderly patients may be the leading cause of ISR. Therefore, we aim to explore the relationship between vascular calcification-associated factors and ISR occurrence. Elderly patients were enrolled according to standard inclusion and exclusion criteria. The serum fibroblast growth factor 23 (FGF23), hypoxia-inducible factor-1α (HIF-1α), and Klotho levels were determined using an enzyme-linked immunosorbent assay. The degree of coronary artery stenosis of the patients with CAD before operation was assessed using the Gensini score. The correlation was analyzed using Pearson analysis. The prediction value was evaluated using receiver operating characteristic (ROC) curve analysis. The patients with CAD were classified into the ISR group with 97 cases and the non-ISR (NISR) group with 349 cases. The Gensini score, serum FGF23, and HIF-1α levels increased while Klotho levels decreased in patients with CAD of the ISR group compared with those of the NISR group. Pearson analysis showed that FGF23 and HIF-1α positively correlated while Klotho negatively correlated to the Gensini score. ROC analysis showed all three factors could effectively predict the occurrence of ISR. Furthermore, the joint had a more effective prediction value for ISR occurrence. The dynamic analysis presented that the serum FGF23 and HIF-1α levels dramatically increased while Klotho levels decreased in patients with CAD after 1-year follow-up. Serum FGF23 and HIF-1α positively correlated while serum Klotho negatively correlated to ISR. Conclusively, these three factors effectively predicted the occurrence of ISR.

Predictive value of bone metabolism markers in the progression of diabetic kidney disease: a cross-sectional study.

This study aimed to investigate the relationship between bone metabolism markers, including serum klotho, fibroblast growth factor 23 (FGF23), 25(OH)D3, iPTH, calcium (Ca), and PHOS and the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Additionally, the predictive value of these markers for DKD progression was evaluated. This study involved 126 patients with T2DM between May 2021 and March 2023. DKD staging was assessed based on urinary protein excretion rates and estimated glomerular filtration rate (eGFR). The study evaluated serum concentrations of klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS across various stages and examined their relationships with clinical parameters. Receiver operating characteristic (ROC) curve analysis was utilized to determine the predictive accuracy of these bone metabolism markers for DKD. Multivariate linear and logistic regression analyses identified risk factors linked to DKD severity. Among the 126 participants, 30 had non-DKD with normal proteinuria, while 96 had DKD, categorized as 31 with stage III DKD (microproteinuria), 34 with stage IV DKD, and 31 with stage V DKD (massive proteinuria). With advancing DKD from stage III to V, levels of klotho, 25(OH)D3, and Ca decreased significantly, whereas FGF23, iPTH and PHOS levels increased markedly. Klotho is significantly positively correlated with eGFR (r = 0.285, P = 0.001.) and negative correlations with serum creatinine (Scr) and UACR (r = -0.255, P = 0.004; r = -0.260, P = 0.011). FGF23 was positively related to systolic blood pressure (SBP) (r = 0.224, P = 0.012), but negatively with eGFR (r = -0.294, P = 0.001). Additionally, 25(OH)D3 exhibited significant negative correlations with several adverse clinical biomarkers, and both iPTH, Ca and PHOS were strongly associated with DKD progression (P<0.05). ROC analysis showed high predictive accuracy for DKD using these bone metabolism markers, with a combined area under the curve (AUC) of 0.846. Multivariate logistic regression analysis reinforced the significance of these markers in DKD progression. Bone metabolism markers, such as klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS are intricately linked to DKD progression and may function as valuable predictive biomarkers.

Phosphaturic Mesenchymal Tumor and Tumor-Induced Osteomalacia: A Report of 5 Cases, Including 2 Skull Base Cases With Arterial Spin Label Perfusion.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired bone mineralization secondary to secretion of fibroblast growth factor 23 (FGF23) from mesenchymal tumors (phosphaturic mesenchymal tumors, PMTs). PMTs have wide anatomical distribution but typically affect extremities and craniofacial bones. Diagnosis of TIO/PMT is often delayed, and a high index of suspicion is essential in patients with unexplained fractures, but many physicians lack familiarity with TIO/PMT and simply attribute fractures to the more common diagnosis of osteoporosis. We present 5 cases of TIO, with 4 having long histories of multiple insufficiency fractures prior to recognition of TIO and localization of a PMT. Four patients were treated surgically, while 1 preferred medical management. Two patients had lesions localized to the skull base, both of which showed marked hypervascularity on arterial spin label perfusion imaging. Thus, arterial spin label may not only help to localize these tumors, but may also be a helpful supplemental imaging finding in supporting this diagnosis. PMT should be considered in the differential diagnosis for hypervascular skull base masses, especially if the patient has any history of insufficiency fracture or imaging evidence of osteopenia, as early diagnosis of TIO can help prevent disabling complications.

Burosumab (Crysvita)

Canada’s Drug Agency recommends that Crysvita be reimbursed by public drug plans for the treatment of X-linked hypophosphatemia (XLH) in adult patients if certain conditions are met. The previous recommendation for Crysvita when initiated in pediatric patients who are at least 1 year of age and in whom epiphyseal closure has not yet occurred, continues to apply to those patients. Crysvita should only be covered to treat patients aged 18 years or older who have a diagnosis of XLH supported by classic clinical features of adult XLH and a confirmed PHEX gene variant, and who have not previously received it. Patients should also have a specific threshold for kidney function or reduced kidney function if it is confirmed not to be due to nephrocalcinosis, bone pain that is caused by XLH or osteomalacia, and have not had a sufficient response to conventional therapy (therapy with active vitamin D and oral phosphate). If a PHEX gene variant is not confirmed, XLH diagnosis can be confirmed with a serum intact fibroblast growth factor 23 (FGF23) level by a Kainos assay. Crysvita should only be reimbursed if it is prescribed by a physician who works in a comprehensive team of health care providers experienced in the diagnosis and management of XLH and if the cost of Crysvita is reduced. Reimbursement may be renewed on an annual basis for patients who do not meet any of the discontinuation criteria, which are the development of hyperparathyroidism, nephrocalcinosis, fasting hypophosphatemia, or fractures or pseudofractures based on X-ray.

Elevation of circulating FGF23 in chronic kidney disease promotes atrial fibrosis through the AKT pathway

Abstract Background The relationship between chronic kidney disease (CKD) and atrial fibrillation (AF) remains unclear. Elevated level of fibroblast growth factor 23 (FGF23) is highly associated with increased cardiovascular disease and mortality in patients suffering from CKD. In recent years, studies have shown that FGF23 promotes cardiac hypertrophy through FGFR4, suggesting that FGF23 may be an important bridge between the heart and kidney. Purpose In this study, we sought to use a well-established rat model of CKD to further characterize the effects of CKD on AF and to identify potential drivers of CKD-induced AF. Methods 14 SD rats were randomly selected to undergo 5/6 nephrectomy and fed for 15 weeks to establish a CKD model, while the SHAM group (8 rats) underwent the same surgery without removing kidney tissue. Body weight, blood pressure, renal function, cardiac ultrasound, epicardial electrocardiography, and pathological indices were monitored in both groups. Gene sequencing was performed on the left atria to search for differentially expressed genes. Rat atrial fibroblasts were selected for further mechanism exploration. We chose TGF-β to stimulate fibroblasts to mimic the process of fibrosis in vivo, and then administered FGFR inhibitors to explore the downstream molecular mechanisms. Results Systolic blood pressure and creatinine were elevated in the CKD group. Compared with the SHAM group, the incidence of AF was significantly higher, left atrial diameter was significantly larger, and epicardial electrical markers showed that left atrial electrical conduction velocity was significantly slower and conduction heterogeneity was significantly increased in the CKD group. Pathologic staining of the left atrium showed significant fibrosis in the CKD group. Consistent with previous findings, FGF23 was significantly elevated in CKD rats. Transcriptomic sequencing revealed that FGFR4 expression was significantly upregulated in the left atrium of CKD rats, The results in rat atrial fibroblasts showed that blocking FGFR4 expression inhibited TGF-β-induced fibrosis and was mediated by the AKT pathway. Conclusions The mechanism of CKD-induced AF is that CKD promotes both structural and electrical remodeling of the atria. Further investigation of its possible downstream molecules revealed that elevated FGF23 in the CKD circulation promotes the development of atrial fibrosis by binding to FGFR4 through the AKT pathway.

Causal association of serum calcium, phosphate, vitamin D, parathyroid hormone, and FGF23 with the risk of aortic stenosis

Abstract Aim Disorders of mineral metabolism, including elevated levels of serum calcium, phosphate, 25-hydroxyvitamin D (25OH-VitD), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), have been reported in patients with calcific aortic valve stenosis (CAVS). However, evidence of the causal role of mineral metabolism in CAVS is still lacking. We aimed to investigate the causality between mineral metabolism and CAVS. Methods A systematic pipeline combining Mendelian randomization (MR), Steiger directionality test, colocalization analysis, protein-protein network, and enrichment analysis was applied to investigate the causal effect. Genome-wide association study (GWAS) and protein quantitative trait loci data for mineral metabolism markers were extracted from large-scale meta-analyses. Summary statistics for CAVS were obtained from two independent GWAS datasets as discovery and replication cohorts (n=374,277 and 653,867). Results In MR analysis, genetic mimicry of serum FGF23 elevation was associated with increased CAVS risk [ORdiscovery=3.081 (1.649-5.760), Pdiscovery=4.21×10-4; ORreplication=2.280 (1.461-3.558), Preplication=2.82×10-4] without evidence of reverse causation (Psteiger=7.21×10-98). Strong colocalisation association with CAVS was observed for FGF23 expression in the blood (PP.H4 = 0.96). Additionally, we identified some protein-protein interactions between FGF23 and known CAVS causative genes. Serum calcium, phosphate, 25OH-VitD, and PTH failed to show causal effects on CAVS at Bonferroni-corrected significance (all P&amp;gt;0.05/5=0.01). Conclusions Elevated serum FGF23 level is a causal risk factor for CAVS, and its mechanism of action in CAVS development may be independent of its function in regulating mineral metabolism. Hence, FGF23 may serve as a circulating marker and a promising preventive target for CAVS, warranting further investigation.

Assessment of experimental circulating biomarkers in volume and pressure overload: insights from a cohort study

Abstract Introduction Experimental biomarkers including Angiopoietin-2 (ANG2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), and insulin-like growth factor-binding protein 7 (IGFBP7) are hypothesized to reflect cardiac pathophysiological processes that are potentially present in adverse cardiac remodeling in volume or pressure overload. This study aims to elucidate the relationship between these circulating biomarkers and the presence of hemodynamically significant pressure or volume overload and adverse outcomes and compare it to N-terminal pro B-type natriuretic peptide (NT-proBNP). Methods We studied the association between the four experimental circulating biomarkers in patients with pressure or volume overload with reference to none/mild valvular disease in N=1302 of an observational outpatient cardiology cohort. The median age was 63.0 (25th/75th quartile 51.5, 71.4) years, 445 (34.2%) were women. Circulating biomarkers were quantified using a novel antibody-based method. Logistic regression models with cox regression plots were employed to assess the association of each biomarker with the severity of valve disease concerning volume or pressure overload, adjusted for age and sex. Results In the overall population, elevated levels of ANG2, BMP10, FGF23 and IGFB7 were positively associated with the presence of significant volume overload (ANG2: Odds ratio (OR) 1.26 (95% confidence interval (CI) 1.17-1.35), p&amp;lt;0.001; BMP10: OR 2.57 (CI 1.89-3.48), p&amp;lt;0.001; FGF23: OR 1.51 (CI 1.14-1.20), p=0.004; IGFBP7: OR 1.39 (CI 1.14-1.69), p=0.001, NT-proBNP: OR 1.69 (CI 1.47-1.95), p&amp;lt;0.001). No statistically significant association between circulating biomarkers and pressure overload was observed. Over a median follow-up of 4 years, 31 (20.1%) participants died in the group of volume overload and 9 (40.9%) individuals in the group of pressure overload. After multivariable-adjustment, elevated levels of BMP 10 showed a borderline association with an increased risk of all-cause mortality in individuals with volume overload compared to none/mild valvular disease: hazard ratio (HR) 1.51 (CI 0.96- 2.38), p=0.075. Higher concentrations of all biomarkers were predictive of all-cause mortality for both individuals with volume overload and those with none/mild valvular disease (ANG2: HR 3.72 (CI 1.67-8.33), p=0.001; BMP10: HR 1.65 (CI 1.20-2.26), p=0.002; FGF23: HR 2.08 (CI 1.65-2.62), p&amp;lt;0.001; IGFBP7: HR 1.55 (CI 1.25-1.91), p&amp;lt;0.001; NT-proBNP: HR 1.72 (CI 1.47-2.00), p&amp;lt;0.001). Conclusions This study demonstrates that circulating biomarkers involved in distinct pathophysiological pathways of inflammation, fibrosis and calcification are elevated in patients with hemodynamically significant volume overload. Since they are also related to mortality, their clinical role needs to be explored further, also in context with the routine biomarker NT-proBNP.

Targeted Deletion of Fibroblast Growth Factor 23 Rescues Metabolic Dysregulation of Diet-induced Obesity in Female Mice.

Fibroblast growth factor 23 (FGF23) is a bone-secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about the nonskeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with a high-fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans. In the present study, we show for the first time that increased circulating FGF23 levels in obese humans correlate with increased expression of adipose Fgf23 and both positively correlate with BMI. To understand the role of adipose-derived Fgf23, we generated adipocyte-specific Fgf23 knockout mice (AdipoqFgf23Δfl/Δfl) using the adiponectin-Cre driver, which targets mature white, beige, and brown adipocytes. Our data show that targeted ablation of Fgf23 in adipocytes prevents HFD-fed female mice from gaining body weight and fat mass while preserving lean mass but has no effect on male mice, indicating the presence of sexual dimorphism. These effects are observed in the absence of changes in food and energy intake. Adipose Fgf23 inactivation also prevents dyslipidemia, hyperglycemia, and hepatic steatosis in female mice. Moreover, these changes are associated with decreased respiratory exchange ratio and increased brown fat Ucp1 expression in knockout mice compared to HFD-fed control mice (Fgf23fl/fl). In conclusion, this is the first study highlighting that targeted inactivation of Fgf23 is a promising therapeutic strategy for weight loss and lean mass preservation in humans.

Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease

BackgroundCarotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)—the earliest detectable serum abnormality associated with CKD-MBD—has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD.MethodsA cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored.ResultsWe recruited 42 children aged 2–18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05).ConclusionsFGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.

Correlation of Plasma Fibroblast Growth Factor 23 with the Risk of Cardiovascular Disease in a Group of Iraqi Patients with Type 2 Diabetes Mellitus

Since it is the largest cause of death globally, cardiovascular disease (CVD) poses a serious health issue. Whether or whether they are changeable, several risk factors exist for the onset of CVD. Conventional and most often used approach to estimate cardiovascular risk is Framingham risk score. Still, ongoing research is looking for alternative markers that can better estimate this risk. One of these producers under increasing research attention is fibroblast growth factor 23 (FGF-23). The aim of this work is to investigate in patients with type 2 diabetes mellitus a possible prognostic value of plasma and urine FGF-23 for CVD. Two groups—the patients' group and the control group—will be formed out of the 200 participants split equally. The group of patients will include those with type 2 diabetes mellitus of more than five years. Using the Framingham risk score, all participants will be evaluated for their 10-year CVD risk; the outcomes will be statistically linked to both plasma and urine FGF-23. Our present work revealed a positive association between Framingham risk and cholesterol, TG, LDL, HDL, VLDL, non-VLDL. and also showed favorable link in Atherogentic index and BMI,HDL,LDL,VLDL and non LDL. In Dm.patient group and farmingham risk, the FGF23 in current study show greater signifcant.

Phosphorous metabolism and manipulation in chronic kidney disease.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome commonly observed in subjects with impaired renal function. Phosphate metabolism has been implicated in the pathogenesis of CKD-MBD and according to the phosphorocentric hypothesis may be the key player in the pathogenesis of these abnormalities. As phosphorous is an essential component for life, absorption from the bowel, accumulation and release from the bones, and elimination through the kidneys are all homeostatic mechanisms that maintain phosphate balance through very sophisticated feedback mechanisms, which comprise as main actors: vitamin D (VD), parathyroid hormone (PTH), calciproteins particles (CPPs), fibroblast growth factor-23 (FGF-23) and other phosphatonins and klotho. Indeed, as the renal function declines, factors such as FGF-23 and PTH prevent phosphate accumulation and hyperphosphatemia. However, these factors per se may be responsible for the organ damages associated with CKD-MBD, such as bone osteodystrophy and vascular calcification. We herein review the current understanding of the CKD-MBD focusing on phosphorous metabolism and the impact of phosphate manipulation on surrogate and hard outcomes.

Tumor-induced phosphopenic osteomalacia: modern approaches to diagnostics and treatment

Phosphopenic osteomalacia (PPOM) is a rare variant of paraneoplastic syndrome caused by tumor synthesis of fibroblast growth factor 23 (FGF23). FGF23 secretion leads to a decrease in phosphate reabsorption and calcitriol levels, which leads to the development of severe hypophosphataemia and hypocalcaemia. FGF23 synthesis is predominantly associated with benign mesenchymal tumors, but has also been described in malignant neoplasms. The main clinical manifestations of PPOM are generalized myalgias and myopathy, ostealgia, pathological fractures, etc. The diagnosis of the disease requires a step-by-step investigation using somatostatin receptor-based imaging techniques, as these have the highest sensitivity for the detection of neoplasms causing osteomalacia. Surgical intervention is clearly the treatment of choice. Promising non-surgical methods include treatment with burosumab and somatostatin analogues.

Hypoxia Activates FGF-23-ERK/MAPK Signaling Pathway in Ischemia-Reperfusion-Induced Acute Kidney Injury

Introduction: Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI. Methods: An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF1α, and ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting was used to measure the phosphorylation of extracellular signal-regulated kinase (ERK) level. Results: In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of ERK (p-ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham-operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, GPx, and p-ERK. In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and p-ERK, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells, but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, pro-inflammatory factor levels, oxidative stress response, and p-ERK levels. Conclusion: FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.

Influence of N- and/or P-restriction on bone metabolism in young goats.

Ruminants can recycle nitrogen (N) and phosphorus (P), which are essential for vital body processes. Reduced N- and P-intake in ruminants is desirable for economic and ecologic reasons. Simultaneous modulation of mineral homoeostasis and bone metabolism occurs in young goats. This study aimed to investigate potential effects of dietary N- and/or P-restriction on molecular changes in bone metabolism. The twenty-eight young male goats were fed a control diet, an N-reduced diet, a P-reduced diet or a combined N- and P-reduced diet for 6-8 weeks. The N-restricted goats had lower plasma Ca concentration and higher plasma osteocalcin (OC) and CrossLaps concentrations. The P-restricted goats had reduced plasma inorganic phosphate (Pi) concentrations and increased plasma Ca concentrations. Due to the initiation of a signalling pathway that inhibits the fibroblast growth factor 23 (FGF23) expression, this was lower with P-restriction. Consequently, lower Pi concentrations were the main factor influencing the reduction in FGF23. The changes in mineral homoeostasis associated with P-restriction led to a reduction in OC, bone mineral content and mineral density. Simultaneously, bone resorption potentially increased with P-restriction as indicated by an increased receptor activator of NF-κB ligand/osteoprotegerin (OPG) ratio and an increase in OPG mRNA expression. Additionally, the increased mRNA expression of the calcitonin receptor during P-restriction points to a higher number of osteoclasts. This study demonstrates an impairment of bone remodelling processes in young goats by N- or P-restriction. With P-restriction, bone mineralisation rate was potentially reduced and bone quality impaired, while with N-restriction, bone remodelling increased.

Vitamin D-Parathyroid Hormone-Fibroblast Growth Factor 23 Axis and Cardiac Remodeling.

Cardiac remodeling is a compensatory adaptive response to chronic heart failure (HF) altering the structure, function, and metabolism of the heart. Many nutritional and metabolic diseases can aggravate the pathophysiological development of cardiac remodeling. Vitamin D deficiency leads to cardiac remodeling by activating the renin-angiotensin-aldosterone system (RAAS), resulting in enhanced inflammation and directly promoting cardiac fibrosis and extracellular matrix deposition. Hyperparathyroidism upregulates protein kinase A or protein kinase C, enhances intracellular calcium influx, promotes oxidative stress, activates RAAS, and increases aldosterone levels, thereby aggravating cardiac remodeling. Besides, fibroblast growth factor 23 (FGF23) plays a direct role in the heart, resulting in ventricular hypertrophy and myocardial fibrosis. Vitamin D deficiency leads to hyperparathyroidism, which in turn increases the level of FGF23. Elevated levels of FGF23 further inhibit vitamin D synthesis. Evidence exists that vitamin D deficiency, hyperparathyroidism, and marked elevations in FGF23 concentration form a vicious cycle and are believed to contribute directly to cardiac remodeling. Therefore, the purpose of this article is to introduce the specific effects of the above substances on the heart and to explain the significance of understanding the vitamin D-parathyroid hormone-FGF23 axis in improving or even reversing cardiac remodeling, thus contributing to the treatment of patients with HF.