Fibroblast Growth Factor 23 to Alpha-Klotho Index Correlates with Systemic Sclerosis Activity: A Proposal for Novel Disease Activity Marker

Systemic sclerosis, a connective tissue disease, is characterized by thickening of the skin, massive fibrosis of internal organs, vasculopathy, and immune system functioning aberration. Recently, vitamin D (VD) deficit, seen almost universally in patients with systemic sclerosis (SSc), has gained much attention. VD metabolism is precisely orchestrated at the level of the kidney by regulators: parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) and their receptors with a FGF23 co-receptor—α-Klotho. The aim of this study was to assess the levels of VD, α-Klotho, FGF23 in SSc patients and to find the relationship between those parameters and disease activity. We enrolled 48 SSc patients with a diffuse variant of SSc and 23 sex- and age-matched healthy volunteers that served as the control group (CG). Patients were characterized by lower level of VD in comparison to CG (19.8 (12.6–28.9) vs. 24.5 (21.3–31.5) ng/mL; p < 0.01), significantly reduced levels of iFGF23 (19.3 (12.1–30.5) vs. 73.9 (59.7–110.2) pg/mL p < 0.001), and similar α-Klotho concentrations (1415 ± 557 vs. 1526 ± 397 pg/mL), respective. None of these parameters correlated with the extent of skin involvement (modified Rodnan Skin Score) and disease activity according to Eustar 2017 guidelines. The FGF23/α-Klotho index was significantly reduced in SSc patients (0.013 (0.0081–0.025) vs. 0.055 (0.038–0.095); p < 0.001), and its log10 correlated (r = 0.35; p < 0.001) with disease activity score (Eular2017). Our data showed that the FGF23/α-Klotho index may be considered as a novel, potential marker of systemic sclerosis activity.

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A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures

Diagnostics ◽

10.3390/diagnostics10030145 ◽

2020 ◽

Vol 10 (3) ◽

pp. 145 ◽

Cited By ~ 1

Author(s):

Fitri Fareez Ramli ◽

Kok-Yong Chin

Keyword(s):

Growth Factor ◽

Fracture Risk ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Fracture Prediction ◽

Current Evidence ◽

Fibroblast Growth ◽

Osteoporosis Screening ◽

Potential Marker ◽

Dickkopf 1

Bone turnover markers (BTMs) derived from the secretory activities of osteoblasts and the matrix-degrading activities of osteoclasts are useful in monitoring the progression of osteoporosis and the efficacy of anti-osteoporotic treatment. However, the usefulness of BTMs in predicting osteoporosis remains elusive. Osteocytes play a central role in regulating bone formation and resorption. The proteins secreted by osteocytes, such as fibroblast growth factor-23 (FGF23), sclerostin (SOST), and dickkopf-1 (DKK1), could be candidates for osteoporosis screening and fracture prediction. This review summarizes the current evidence on the potential of osteocyte-related proteins as biomarkers for osteoporosis and fracture prediction. The literature reports that SOST may be a potential marker for osteoporosis screening but not for fracture prediction. FGF23 is a potential marker for increased fracture risk, but more studies are needed to confirm its usefulness. The role of DKK1 as a marker to predict osteoporosis and fracture risk cannot be confirmed due to a lack of consistent evidence. In conclusion, circulating osteocyte markers are potential osteoporosis biomarkers, but more studies are warranted to validate their clinical use.

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Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

Cardiorenal Medicine ◽

10.1159/000440984 ◽

2015 ◽

Vol 6 (1) ◽

pp. 73-82 ◽

Cited By ~ 9

Author(s):

Shahanas Chathoth ◽

Samir Al-Mueilo ◽

Cyril Cyrus ◽

Chittibabu Vatte ◽

Awatif Al-Nafaie ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Control Group ◽

Phosphorus Metabolism ◽

Fibroblast Growth ◽

Saudi Population ◽

Fgf23 Level

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 the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

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Fibroblast Growth Factor 21 in Patients with Acromegaly

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-115647 ◽

2017 ◽

Vol 125 (10) ◽

pp. 649-654 ◽

Cited By ~ 3

Author(s):

Jowita Halupczok-Żyła ◽

Aleksandra Jawiarczyk-Przybyłowska ◽

Marek Skrzypski ◽

Mathias Strowski ◽

Marek Bolanowski

Keyword(s):

Growth Factor ◽

Disease Activity ◽

Fibroblast Growth Factor ◽

Body Mass ◽

Hdl Cholesterol ◽

Fibroblast Growth Factor 21 ◽

Control Group ◽

Fibroblast Growth ◽

Anthropometric Parameters ◽

Cholesterol Levels

Abstract Introduction The goal of the study was to investigate fibroblast growth factor-21 (FGF-21) levels in acromegalic patients in relation to the disease activity and to compare them with controls. Further, we aimed to evaluate the associations between FGF-21 and random growth hormone (GH), insulin-like growth factor-1 (IGF-1), metabolic and anthropometric parameters. Materials and methods The study group consisted of 50 acromegalic patients divided into 3 subgroups on the basis of disease activity (AA – active acromegaly, CD – controlled disease, CA – cured acromegaly). 27 subjects were assigned to the control group (CG). Blood samples were obtained from all participants to assess FGF-21, GH, IGF-1, lipids, glucose and insulin levels. Body mass, body mass index and body composition were also evaluated. Results There were no statistically significant differences in FGF-21 concentrations across all groups despite of subjects classification. FGF-21 correlated positively with random GH in the groups: CA, CD+CA, AA+CD+CA (r=0.48, p=0.049; r=0.39, p=0.023; r=0.33, p=0.02; respectively); with IGF-1 in the AA+CD+CA group (r=0.29, p=0.041); with triglycerides in the following groups: CD, CD+CA, AA+CD+CA (r=0.63, p=0.08; r=0.44, p=0.01; r=0.37, p=0.007; respectively) and with age in the CG and CD+CA groups (r=0.41, p=0.029; r=0.42, p=0.029; respectively). There were statistically significant negative correlations between FGF-21 and HDL-cholesterol levels in the groups: CD, CD+CA, AA+CD+CA (r=-0.53, p=0.03; r=-0.37, p=0.032; r=-0.29, p=0.036, respectively). Conclusions FGF-21 levels were similar in patients with acromegaly compared to controls. However, our results indicate that FGF-21 may have a potential role in the development of acromegaly complications.

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AB0884 Serum fibroblast growth factor-23 levels were higher in patients with axial spondyloartrhritis and may be associated with disease activity

10.1136/annrheumdis-2018-eular.2828 ◽

2018 ◽

Author(s):

O. Gercik ◽

E. Coban ◽

B. Ozbek Iptec ◽

G. Avcioglu ◽

D. Solmaz ◽

...

Keyword(s):

Growth Factor ◽

Disease Activity ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth

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Fibroblast growth factor-23 in patients with systemic sclerosis: A case–control study

The Egyptian Rheumatologist ◽

10.1016/j.ejr.2014.12.007 ◽

2016 ◽

Vol 38 (2) ◽

pp. 105-109 ◽

Cited By ~ 4

Author(s):

Saeedeh Shenavandeh ◽

Sara Radmanesh ◽

E. Kamali Sarvestani ◽

M.A. Nazarinia ◽

Gholamhossein R. Omrani

Keyword(s):

Systemic Sclerosis ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Case Control Study ◽

Fibroblast Growth Factor 23 ◽

Case Control ◽

Fibroblast Growth ◽

Control Study

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Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

American Journal of Nephrology ◽

10.1159/000489964 ◽

2018 ◽

Vol 47 (6) ◽

pp. 406-414 ◽

Cited By ~ 13

Author(s):

Noriaki Maruyama ◽

Tomoyasu Otsuki ◽

Yoshinori Yoshida ◽

Chinami Nagura ◽

Maki Kitai ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Hemodialysis Patients ◽

Serum Phosphate ◽

Lanthanum Carbonate ◽

Ferric Citrate ◽

Control Group ◽

Serum Phosphate Level ◽

Fibroblast Growth

Background: Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. Methods: This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. Results: FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline –6,160 vs. –1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). Conclusion: In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level.

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AB0405 FIBROBLAST GROWTH FACTOR-23 IS ASSOCIATED WITH HIGH-DENSITY LIPOPROTEIN IN SYSTEMIC SCLEROSIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.302 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1231.1-1231

Author(s):

A. Alvarez de Cienfuegos ◽

L. Cantero-Nieto ◽

J. A. García-Gómez ◽

R. Ríos Fernández ◽

J. Martin Ibanez ◽

...

Keyword(s):

Systemic Sclerosis ◽

Growth Factor ◽

High Density Lipoprotein ◽

Fibroblast Growth Factor ◽

Lupus Erythematosus ◽

Fibroblast Growth Factor 23 ◽

Density Lipoprotein ◽

High Density ◽

Healthy Controls ◽

Fibroblast Growth

Background:Systemic sclerosis (SSc) is characterized by calcification, vasculopathy, and endothelial wall damage, all of which can increase the risk for atherosclerosis and cardiovascular disease. Mechanisms by which atherosclerosis is promoted in connective tissue diseases remain unknown, but is believed to be secondary to chronic inflammation, altered lipid profiles and function, autoantibodies, and endothelial dysfunction. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has been implicated as a putative pathogenic factor in cardiovascular disease. FGF23 could exert hormonal control on fat mass and glucose metabolism, since it shares structural similarities with the other FGF subfamily members (FGF15/19 and FGF21) that are involved in carbohydrate and lipid metabolism.Objectives:The objectives of this study were: to compare serum FGF23 levels between SSc patients and healthy controls and to investigate possible associations between FGF23 and serum lipid profile in SSc patients.Methods:This cross-sectional study was performed in San Cecilio Hospital, Granada (Spain) from November 2017 to May 2019. Sixty-two women with SSc and 62 age and sex matched healthy controls were enrolled in this study. All patients included in this study had normal serum creatinine (Cr) levels and met the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for SSc. Total cholesterol and triglyceride levels were determined by fully enzymatic techniques. High-density lipoprotein (HDL) was determined after precipitation of apolipoprotein B (apoB)–containing lipoproteins with magnesium sulfate and dextran sulfate. Low-density lipoprotein (LDL) was calculated using the Friedewald formula. Serum FGF23 was analyzed using ELISA.Results:A total of 62 female patients were included in our study, with a mean (SD) age of 53 ± 10 years. The majority were Caucasian (90.5%). The mean disease duration was 8.8 ± 6.9 years. Forty-four (70.9%) patients had a limited form of the disease and 18 (29.1%) had a diffuse form.There was no significant differences in FGF23 levels between the patients and controls (78.2 ± 60.5 vs. 80.3 ± 56.3 pg/mL, p= 0.662), but we found a statistically significant inverse relationship between FGF23 and HDL-c measurements (r= -0.27; p= 0.03) in women with SSc. In addition, in the linear regression model, higher FGF23 concentrations were associated with lower HDL-c [β = -1.45 95% CI (-2.81, -0.08); p < 0.05].Conclusion:We report an association between circulating FGF23 and HDL-c in SSc female patients, representing a novel pathway linking high FGF23 to an increased cardiovascular risk.References:[1]Ho M, Veale D, Eastmond C, et al. Macrovascular disease and systemic sclerosis. Ann Rheum Dis. 2000; 59(1):39–43.[2]McMahon M, Grossman J, FitzGerald J, et al. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 2006; 54(8):2541–9.[3]O’Neill SG, Giles I, Lambrianides A, et al. Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 2010; 62(3):845–54.[4]Mirza MA, Alsio J, Hammarstedt A, et al. Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler Thromb Vasc Biol. 2011; 31:219–227.Disclosure of Interests:None declared

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Fibroblast growth factor-23 concentrations in polycystic ovary syndrome

Turkish Journal of Biochemistry ◽

10.1515/tjb-2016-0307 ◽

2017 ◽

Vol 43 (1) ◽

pp. 83-88 ◽

Cited By ~ 1

Author(s):

Seyfullah Kan ◽

Muhammed Kızılgül ◽

Cavit Çulha ◽

Müyesser Sayki Arslan ◽

Mahmut Apaydın ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Polycystic Ovary ◽

Fibroblast Growth Factor 23 ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Total Testosterone ◽

Fibroblast Growth ◽

Metabolic Disturbances ◽

Pcos Group

AbstractObjective:This study was designed to compare the serum concentrations of Fibroblast growth factor 23 (FGF23) among patients with PCOS and healthy subjects and to evaluate the relation between the hormonal and metabolic parameters.Methods:Forty patients with PCOS were compared with 40 healthy individuals in a case-control study design. The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group 2003 guideline criteria were used in the diagnosis of PCOS. Serum intact FGF23 concentrations were determined by enzyme-linked immunosorbent assay (ELISA).Results:Mean serum FGF23 concentrations were similar between PCOS group and control group (19.73±16.75 pg/mL and 17.20±9.26 pg/mL, p>0.05). Waist circumference, hip circumference, total testosterone, Ferriman-Gallwey (FG) score and hsCRP were significantly higher in the PCOS group (p<0.001). The concentrations of LH, DHEA-S, FSH, insulin, total cholesterol, triglyceride, HOMA-IR were significantly higher in the PCOS group when compared to control group (p<0.05). FGF23 concentrations did not correlate with BMI, fasting glucose and insulin, HOMA-IR and lipid parameters.Conclusions:FGF23 concentrations were similar in the PCOS group compared with the non-PCOS control group. The present findings may suggest that FGF23 is not a useful marker of metabolic disturbances including insulin resistance, dyslipidemia, and obesity in PCOS.

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