FGF23, Biomarker or Target? (original) (raw)
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The significance of Fibroblast growth factor 23 (FGF-23) in humans
Journal "Medicine", 2021
Nowadays chronic kidney disease (CKD) is one of the leading chronic non-communicable diseases in terms of morbidity and mortality. One of the most serious complications is mineral-bone disorder, which worsen the clinical course and prognosis of patients. Fibroblast growth factor 23 (FGF-23) is a new biomarker that regulates phosphate metabolism and plays an important role in the pathogenesis of many complications in CKD. Purpose. To study the physiological role of FGF-23, as well as its potential clinical significance in the progression of CKD and its complications. Material and methods. A 20-year-deep literature search was conducted in the international scientific databases PubMed / Medline, Web of Science and Google Scholar for the following keywords: "Fibroblast growth factor 23", "FGF-23", "phosphate homeostasis", "chronic kidney disease", "Mineral and bone disorders", "left ventricular hypertrophy". Results and discuss...
International journal of hypertension, 2014
Patients with chronic kidney disease (CKD) are at increased risk of mortality, mainly from cardiovascular disease. Moreover, abnormal mineral and bone metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our understanding of CKD-MBD and has revealed more complex cross-talk and endocrine feedback loops between the kidney, parathyroid gland, intestines, and bone. During the past decade, reports of clinical studies have described the association between FGF23 and cardiovascular risks, left ventricular hypertrophy, and vascular calcification. Recent translational reports have described the existence of FGF23-Klotho axis in the vasculature and the causative effect of FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD ...
Physiological Actions of Fibroblast Growth Factor-23
Frontiers in Endocrinology
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone suppressing phosphate reabsorption and vitamin D hormone synthesis in the kidney. At physiological concentrations of the hormone, the endocrine actions of FGF23 in the kidney are αKlothodependent, because high-affinity binding of FGF23 to FGF receptors requires the presence of the co-receptor αKlotho on target cells. It is well established that excessive concentrations of intact FGF23 in the blood lead to phosphate wasting in patients with normal kidney function. Based on the importance of diseases associated with gain of FGF23 function such as phosphate-wasting diseases and chronic kidney disease, a large body of literature has focused on the pathophysiological consequences of FGF23 excess. Less emphasis has been put on the role of FGF23 in normal physiology. Nevertheless, during recent years, lessons we have learned from loss-of-function models have shown that besides the paramount physiological roles of FGF23 in the control of 1α-hydroxylase expression and of apical membrane expression of sodium-phosphate co-transporters in proximal renal tubules, FGF23 also is an important stimulator of calcium and sodium reabsorption in distal renal tubules. In addition, there is an emerging role of FGF23 as an auto-/paracrine regulator of alkaline phosphatase expression and mineralization in bone. In contrast to the renal actions of FGF23, the FGF23-mediated suppression of alkaline phosphatase in bone is αKlotho-independent. Moreover, FGF23 may be a physiological suppressor of differentiation of hematopoietic stem cells into the erythroid lineage in the bone microenvironment. At present, there is little evidence for a physiological role of FGF23 in organs other than kidney and bone. The purpose of this mini-review is to highlight the current knowledge about the complex physiological functions of FGF23.
FGF23: A Review of Its Role in Mineral Metabolism and Renal and Cardiovascular Disease
Disease Markers
FGF23 is a hormone secreted mainly by osteocytes and osteoblasts in bone. Its pivotal role concerns the maintenance of mineral ion homeostasis. It has been confirmed that phosphate and vitamin D metabolisms are related to the effect of FGF23 and its excess or deficiency leads to various hereditary diseases. Multiple studies have shown that FGF23 level increases in the very early stages of chronic kidney disease (CKD), and its concentration may also be highly associated with cardiac complications. The present review is limited to some of the most important aspects of calcium and phosphate metabolism. It discusses the role of FGF23, which is considered an early and sensitive marker for CKD-related bone disease but also as a novel and potent cardiovascular risk factor. Furthermore, this review gives particular attention to the reliability of FGF23 measurement and various confounding factors that may impact on the clinical utility of FGF23. Finally, this review elaborates on the clinica...
CLINICAL AND BIOCHEMICAL STUDY OF FIBROBLAST GROWTH FACTOR 23 IN CHRONIC KIDNEY DISEASE.
Understanding the contributory role of increased fibroblast growth factor23 (FGF23) and secondary hyperparathyroidism to changes in minerals and bone metabolism among chronic kidney disease (CKD) patients is a challenge. So the present study aimed to evaluate the role of FGF23 in CKD of various grades and potential utility for early diagnosis of disturbed bone and mineral metabolism among such patients. This hospital based-cross sectional study has been conducted on 100 CKD patients of various grades. Colorimetric assays of serum urea, creatinine, phosphorous and calcium, while, ELISA assays of parathormone hormone (PTH) and FGF23, were done to all included patients. The overall results showed frequent abnormally high serum FGF23 among CKD grade 3 and 4 compared to other grades. Also there was significant positive correlation between the serum FGF234 levels and the CKD grade (r=0.21, p = 0.03). Significant positive correlations between serum levels of FGF23 vs. both urea and PTH (r=0.19, p=0.04 and r= 0.31, p=0.002 respectively) with significant negative correlations between serum FGF23 levels vs. both total calcium and eGFR (r=-0.21, p=0.02 and r=- 0.39, p=0.0001 respectively). There were non-significant correlations between serum FGF23 and age, weight, height, BMI and phosphorous (p˃0.05). FGF23 is better negative than positive predictive biomarker for calcium and phosphorous disturbances in CKD patients at cut off point 2.9 and 3.1 pg/ml respectively. In conclusion, FGF23 is an emerging biomarker in CKD and its follow up measurement could be helpful for early diagnosis of CKD-MBD.
PRILOZI, 2017
Fibroblast Growth Factor (FGF)-23 increase is considered one of the earliest biochemical abnormalities in chronic kidney disease-mineral bone disorder (CKD-MBD). Furthermore, accumulating data have provided evidence of a link between increased FGF-23 levels and cardiovascular morbidity and mortality in CKD patients as well as in several other populations including cardiology patients and general population. The cellular and molecular mechanisms underlying the deleterious effect of FGF-23 on the cardiovascular system are not yet completely defined and are the focus of intense research. However, animal and human studies have demonstrated important actions of FGF-23 in the heart and vessels through which could promote the development of cardiovascular complications in uremia. Moreover, significant interactions have been reported between FGF-23 and other well recognized cardiovascular risk factors such as renin-angiotensin system and inflammation which could account, at least in part, for the observed associations between FGF-23 and adverse clinical outcomes. Further studies are needed to clarify the mechanisms responsible for the pleiotropic actions of FGF-23 and moreover to identify whether it is a modifiable risk factor and a potential target of therapeutic interventions which could probably help to reduce the unacceptably high cardiovascular morbidity and mortality of CKD patients.
FGF-23 in children with CKD: a new player in the development of CKD-mineral and bone disorder
Nephrology Dialysis Transplantation, 2012
Disturbances in mineral and bone metabolism in children with chronic kidney disease (CKD) lead to specific abnormalities of skeletal homeostasis called CKD-mineral and bone disorder (CKD-MBD). These disturbances should be diagnosed and managed appropriately to prevent bone deformities and disturbed growth. Changes in the vitamin D and parathyroid hormone (PTH), and the subsequent alterations in calcium (Ca) and phosphate (P) homeostasis are considered responsible for the development of CKD-MBD. Recently, a phosphaturic hormone, the fibroblast growth factor-23 (FGF-23), has been reported as a key regulator of P and vitamin D metabolism. A number of recent studies in paediatric populations have documented that the FGF-23 levels are increased early in CKD, before any abnormalities in serum Ca, P or PTH are apparent. The elevated FGF-23 levels result in a negative P balance to maintain P homeostasis, inducing phosphaturia, independently of PTH, and suppressing vitamin D synthesis. Therefore, the bonekidney-parathyroid endocrine axis mediated by FGF-23 should be a novel therapeutic target in clinical practice, even in early stages of CKD in children.
Cardiorenal Medicine, 2015
Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that ...