Fibroblast Growth Factor 23 Values Research Articles

#2009 FGF23 in patients with diabetic kidney disease and atherosclerosis

Abstract Background and Aims Diabetes mellitus (DM) and chronic kidney disease (CKD) are risk factors for vascular atherosclerosis, a pathological process with an important inflammatory component. The coexistence of these conditions in patients with diabetic kidney disease (DKD) has additive effects with worst cardiovascular mortality and morbidity rates when compared to non-diabetic CKD patient on cardiovascular outcomes. Accumulating research has shown that increased levels of bone-derived fibroblast growth factor 23 (FGF23), the major phosphate-regulating hormone, constitute a novel predictor of cardiovascular and all-cause mortality in CKD patients, with potential effects on disorders of glucose metabolism as well. The objective of this comparative study is to determine the differences in FGF23 levels in two groups of patients with CKD, with and without DM, matched by age, sex and renal function, all of them with clinical atherosclerotic disease. We also evaluated the relationships of FGF23 with several inflammatory markers and parameters of glucose metabolism. Method Sixty-six patients with CKD stages 3-4 (33 of them with DM) and diagnosed with peripheral vascular disease were included in the study. Whole blood and serum samples were obtained from all participants. CRP values, neutrophil/lymphocyte (N/L) ratio, HbA1c (%), fasting glucose, and Triglycerides and glucose (TyG) index, among other parameters, were obtained using standardized routine methods. Circulating levels of the intact form of FGF23, tumor necrosis factor (TNF) α, interleukin (IL) 6, and IL10 were determined by ELISA immunoassays in both groups. We also performed gene expression analysis for these three cytokines in peripheral blood cells (PBCs) using qPCR. Results The mean values of eGFR, ACR and phosphate were 37.6 ± 11.2 ml/min/1.73 m2; 294.1 ± 271.2 mg/g; 3.8 ± 0.82 mg/dL; respectively without differences between patients with and without DM The median circulating FGF23 values were higher in the DM group (51.59 [37.73-89.68] vs. 38.1 [33-54.14] pg/mL; p<0.001). Likewise, patients with DM presented higher levels of TNFα both in serum concentration (1.78 [0.72-2.47] vs. 1.28 [1.01-1.88] pg/mL; p<0.01) as in the expression of mRNA in PBCs (2.1 ± 1.26 vs. 1.87 ± 1.16 a.u.; p<0.05). No differences were observed for IL6 and IL10 levels, nor for CRP concentration or N/L ratio. As expected, fasting glucose, HbA1c and TyG index were higher in the group of subjects with DM. FGF23 was inversely correlated with eGFR (r=−0.435, p<0.0001), while it showed a positive association with ACR (r=0.416, p<0.001) and, interestingly, with proinflammatory cytokines including circulating TNFα (r=0.44, p<0.001), circulating IL6 (r=0.27, p=0.04), and TNF mRNA expression in PBCs (r=0.245, p=0.047). Furthermore, circulating FGF23 was also direct and significantly correlated with HbA1c (r=0.34, p<0.01). Conclusion These results suggest that FGF23 levels are higher in DKD than in non-DM CKD patients with similar renal function. DKD patients also had higher levels of the proinflammatory cytokine TNFα. Our results also show positive correlations of FGF23 with the inflammatory cytokines TNFα and IL6, as well as with HbA1c. Previous studies, shown that elevated TNFα and glucose promote FGF23 production, which may help to explain the higher levels of FGF23 in patients with DM Future studies should clarify whether FGF23 is simply a marker of atherosclerosis disease severity or a contributing factor to this complication in CKD.

The prognostic significance of fibroblast growth factor-23 in predicting complications of type 2 diabetes mellitus, especially when associated with obesity

type 2 Diabetes Mellitus (T2DM) is considered a global health problem with an exceptionally high economic burden not only for families but also for countries overall. In 90-95% of T2DM cases, varying degrees of obesity are observed. One aspect contributing to complications in T2DM involves musculoskeletal system impairment, specifically alterations in bone mineral density (BMD), indicative of bone architecture disruption, leading to secondary osteoporotic conditions. Fibroblast growth factors (FGFs), known for their regulatory influence on metabolism, are identified as mechanisms activated in T2DM. Within this group, fibroblast growth factor 23 (FGF-23) is acknowledged. In individuals with T2DM and excess weight or obesity, conditions conducive to increased FGF-23 synthesis are established, contributing to disturbances in mineral metabolism. Therefore, our study aimed to investigate the content and role of FGF-23 in the development of secondary osteoporosis in T2DM patients with concurrent obesity. A total of 103 patients with type 2 diabetes were involved, with 83 cases featuring elevated body weight or obesity (main group). To assess the impact of obesity on FGF-23 changes, a comparison group of 20 T2DM patients with normal body weight (NBW) was formed. The average age of patients with comorbid conditions was 43±4.6 years, and for those with isolated T2DM, it was 44.1±2.1 years. The average duration of T2DM across groups ranged from 1 to 13 years (6.7±2.4 years on average). Control FGF-23 values were obtained from a group of 20 practically healthy individuals of similar age and gender. The diagnosis of T2DM was confirmed according to the Unified Medical Assistance Protocol "Diabetes Mellitus" (Order of the Ministry of Health of Ukraine dated December 21, 2012, No. 1118). Thus, all examined T2DM patients were in the subcompensation stage with a moderate degree of disease severity. The presence and severity of obesity were assessed according to the International Diabetes Federation (IDF, 2005) criteria based on the body mass index (BMI) calculation using the Ketle formula. In the examination of 83 T2DM patients with obesity, a probable increase in fibroblast growth factor 23 (FGF-23) in serum was determined, correlating with osteoporotic changes in dual-energy X-ray absorptiometry. Therefore, FGF-23 can be utilized as a marker for bone mineral density status and control of treatment measures.

The correlation between serum fibroblast growth factor-23 levels and left ventricular hypertrophy in chronic kidney disease patients

Introduction: Hyperphosphatemia in chronic kidney disease (CKD) patients can stimulate the production of the fibroblast growth factor-23 (FGF-23) phosphatonin hormone, which is associated with cardiac remodeling resulting in left ventricular hypertrophy (LVH). Objectives: To determine the correlation between FGF-23 level and LVH incidence in CKD patients and establish the associated risk factors. Materials and Methods: This cross-sectional study involved 74 CKD patients who were classified as stage 3 (n=18), stage 4 (n=17), stage 3 (n=18), dialysis stage 5 (n=20), or non-dialysis stage 5 (n=19). The FGF-23 levels of the patients were measured using the ELISA (enzyme-linked immunosorbent assay) kit method, whereas a cardiologist verified LVH using an echocardiographic examination based on the LVH criteria of >95 g/m2 for females and >115 g/m2 for males. Results: A significant difference was observed in the mean FGF-23 values between the LVH and non-LVH patients (443.27±437.047 RU/mL and 172.68±185.56 RU/mL, respectively; P<0.05). The receiver operating characteristics revealed that patients with FGF-23 levels >123.95 RU/mL had a 3.6 times greater risk of LVH compared to those with values ≤123.95 RU/mL. The LVH risk factors of gender and age, as well as hypertension, diabetes mellitus, and obesity diagnoses were not associated with LVH incidence in CKD patients. Conclusion: A significant association was found between FGF-23 level and LVH incidence in CKD patients, in which an FGF-23 level >123.95 RU/mL corresponded to a 3.6 times greater risk of LVH than those with FGF-23 levels below this value.

Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children

To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children. A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed. The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05). Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Occipital bone and tumor-induced osteomalacia: a rare tumor site for an uncommon paraneoplastic syndrome

IntroductionTumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome due to the overproduction of fibroblast growth factor 23 (FGF23). It is predominantly caused by mesenchymal tumors and cured upon their complete removal. Non-surgical treatment is an alternative option but limited to specific clinical conditions.MethodsWe report a challenging case of TIO caused by a tumor involving the occipital bone. We also performed a literature review of TIO caused by tumors localized at this site, focusing on clinical findings, treatment, and outcomes.ResultsThe patient, a 62-year-old male, presented with a long-lasting history of progressive weakness. Biochemical evaluation revealed severe hypophosphatemia due to low renal tubular reabsorption of phosphate with raised intact FGF23 values. A 68 Ga-DOTATATE PET/TC imaging showed a suspicious lesion located in the left occipital bone that MRI and selective venous catheterization confirmed to be the cause of TIO. Stereotactic gamma knife radiosurgery was carried out, but unfortunately, the patient died of acute respiratory failure.To date, only seven additional cases of TIO have been associated to tumors located in the occipital bone. Furthermore, the tumor involved the left side of the occipital bone in all these patients.ConclusionThe occipital region is a difficult area to access so a multidisciplinary approach for their treatment is required. If anatomical differences could be the basis for the predilection of the left side of the occipital bone, it remains to be clarified.

#3115 THE ASSOCIATION OF FIBROBLAST GROWTH FACTOR-23 AND CARDIORENAL SYNDROME IN PATIENTS WITH DIABETES MELLITUS

Abstract Background and Aims Previous studies suggest that interactions between the heart and the kidney can contribute to the progressive dysfunction of both organs. Recently, there has been an increase in the prevalence of cardiovascular disease (CVD) and chronic kidney disease (CKD) due to increasing diabetes mellitus rate. It is known that fibroblast growth factor-23 (FGF-23) has been found to be related to kidney metabolism especially as a biomarker and a key factor to be used in the kidney field. The aim of our study was to assess potential therapeutic approaches of the use of FGF-23 in clinical settings as a potential circulating biomarker for CVD and CKD. Method A total of 155 patients with DT2, aged 34 to 84 years (60 [60;72]), were examined. Control group included 94 healthy people the same age. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of FGF-23 in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics. Results The levels of FGF-23 were significantly higher in DT2 patients with CKD 5 in comparison with stages 1–4. There were positive strong significant association between FGF-23 and creatinine (r = 0.71, p&amp;lt;0.001). In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR; 95% CI 1.890; 1.362-2.622, p&amp;lt;0,001). When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 was 0,9 pmol/l. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively (AUC 0.832±0.035 with 95% CI: 0.764-0.901, p&amp;lt;0.001). DT2 patients with left ventricular hypertrophy (LVH) were characterized by higher levels of FGF-23 (2,45 [0,65;7,43] vs 0,57 [0,19;2,19] pmol/l in control group). DT2 patients with LVH and natriuretic peptides levels ≥ 35 pg/ml for BNP and/or ≥125 ng/ml for NT-proBNP had significantly high concentrations of FGF-23 than patients with normal levels of natriuretic peptides (3,22 [1,09;9,55] vs. 0,52 [0,27;1,08] pmol/l, p&amp;lt;0,0001). In order to assess the diagnostic significance of the FGF-23 for predicting left ventricular mass index (LVMI) thickening and increasing the proBNP concentration, a ROC analysis was performed. Thus, at the level of FGF-23 (AUC-0.702) = 0.9 pmol/l, the sensitivity and specificity for LVMI thickening were 66.9% and 67.3%. Conclusion Our study identifies FGF-23 as a promising target of novel therapeutic interventions in cardiorenal syndrome, which should be investigated in future clinical studies.

Fibroblast growth factor 23 in children with or without heart failure: a prospective study

BackgroundElevated fibroblast growth factor 23 (FGF23) levels have been associated with mortality in adults with heart failure (HF), but data on FGF23 levels in paediatric HF are limited. In this...

Correlation of FGF-23 With Biochemical Markers and Bone Density in Chronic Kidney Disease-Bone Mineral Density Disorder.

Aim The purpose of this study was to determine the relationship between biochemical markers such as serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), 25(OH) vitamin D, and fibroblast growth factor 23 (FGF23) in our study group, as well as to correlate dual-energy X-ray absorptiometry (DEXA) findings with these biochemical markers. Methodology An eligible group of 50 chronic hemodialysis (HD) patients, age 18 and older, who have undergone HD two times a week for at least six months participated inthis retrospective cross-sectional study. We compared serum FGF23, intact parathyroid hormone (iPTH), 25(OH) vitamin D, calcium, phosphorus, and dual-energy X-ray absorptiometry scan showing bone mineral density disorder (BMD) around the femoral neck, distal radius, and lumbar spine. Human FGF23 Enzyme Linked Immuno Sorbent Assay (ELISA) Kit PicoKine®(Catalog # EK0759; Boster Biological Technology, Pleasanton, CA) was used in the optimum moisture content (OMC) lab to measure FGF23 levels. For the analysis of associations with various studied variables, the levels of FGF23 were split into two groups, which were high (group 1, FGF23 50 to 500 pg/ml), that is, up to 10 times the normal levels and extremely high (group 2, FGF23 > 500 pg/ml) FGF23 levels. All the tests were conducted for routine examination where the data obtained was analyzed in this research project. Results The mean age of patients was 39.18 ±12.84 years, of whom 35 (70%) were males and 15 (30%) were females. For the entire cohort, serum PTH levels were consistently high, and vitamin D levels were low. FGF23 levels were high in the whole cohort. The average iPTH concentration was 304.20 ± 113.18 pg/ml, while the average 25(OH) vitamin D concentration was 19.68±7.49 ng/ml. The mean FGF23 levels were 1877.36±1378.67 pg./ml. The mean calcium value was 8.23±1.05 mg /dl and the mean phosphate of 6.56±2.28 mg /dl. In the whole cohort, FGF23 showed a negative correlation with vitamin D and a positive correlation with PTH, but not statistically significant. Extremely high FGF23 levels were associated with lower bone densitycompared to high FGF23 values. Considering that in the whole cohort of patients, only nine had high FGF-23 and the rest of 41 patients had extremely high FGF23, we could not ascertain differences in PTH, calcium, phosphorus, and 25(OH) vitamin Dlevels between the two groups. The average length of time on dialysis was eight months, and there was no link between FGF-23 levels and the length of time on dialysis. Conclusion Bone demineralization and biochemical abnormalities are a hallmark in chronic kidney disease (CKD) patients. Abnormalities in serum phosphate, parathyroid hormone, calcium, and 25(OH) vitamin Dplay critical roles in the development of BMD in CKD patients. With the discovery of FGF-23 as a biomarker that is increased early in CKD patients, new questions arise about the effects and actions of FGF-23 in controlling bone demineralization and other biochemical markers. Our study found no statistically significant correlation to suggest an effect of FGF-23 on these parameters. But the findings need to be looked at more in prospective, controlled research, especially to find out if therapies that successfully target FGF-23 can make a big difference in how people with CKD feel about their health.

Circulating Fibroblast Growth Factor-23 Levels Can Predict Rapid Kidney Function Decline in a Healthy Population: A Community-Based Study

Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD-a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

Fibroblast growth factor 23 as a predictor of left atrial appendage thrombosis in patients with nonvalvular atrial fibrillation and various risk of stroke

Aim. To study the role of fibroblast growth factor 23 (FGF-23) as a predictor of left atrial appendage (LAA) thrombosisin patients (pts) with non-valvular atrial fibrillation (AF) and different risk levels of thromboembolic complications (TEC) according to the CHA2DS2-VASc score.Methods. The study included 250 pts with non-valvular AF hospitalized for radiofrequency ablation, divided into 2 groups: group (gr.) 1 - with 0-1 points (n=79) and gr.2 - with ≥2 points on the CHA2DS2-VASc scale (n=171). According to the results of transesophageal echocardiography, pts of each group were divided into subgroups depending on the presence of LAA thrombosis, which was found in 19 pts of gr.1 and 72 of gr.2. Patients underwent transthoracic echocardiography, determination of blood biomarkers: NT-proBNP (pg/ml), GDF-15 (pg/ml), FGF-23 (pmol/l), highly sensitive C-reactive protein (mg/l), cystatin C (mg/l).Results. Pts with LAA thrombosis in both groups had in common: a longer history of arterial hypertension, a greater proportion of coronary artery disease and persistent AF, lower GFR, higher values of atrial volume indices, left ventricle myocardial mass, systolic pressure in the pulmonary artery, median NT-proBNP, FGF-23 and GDF-15. Logistic regression analysis performed separately in the groups revealed the same independent predictors of LAA thrombosis in both groups: LA volume index (LAVI) and the level of FGF-23 in the blood. At the same time, the threshold value of FGF-23, separating pts by the presence of LAA thrombosis, was higher in gr.1 (≥0.85 and ≥0.5 pmol/l, respectively), and the area under the AUC curve for FGF-23 in gr.1 was greater: 0.964 vs 0.865 in gr.2 (p=0.026).Conclusion. The serum level of FGF-23, along with the LAVI, is an independent predictor of LAA thrombosis in pts with AF and various risk of TEC according to CHA2DS2-VASc; the threshold level of FGF-23 for pts at low risk of TEC is significantly higher than for high risk pts, and allows more accurate prediction of the presence of LAA thrombosis.

Low Klotho/Fibroblast Growth Factor 23 Ratio Is an Independent Risk Factor for Renal Progression in Chronic Kidney Disease: Finding From KNOW-CKD.

BackgroundWe aimed to evaluate soluble Klotho and circulating fibroblast growth factor 23 (FGF23) ratio as a risk factor for renal progression, cardiovascular (CV) events, and mortality in chronic kidney disease (CKD).MethodsWe analyzed 2,099 subjects from a CKD cohort whose soluble Klotho and C-terminal FGF23 levels were measured at enrollment. The Klotho to FGF23 ratio was calculated as Klotho values divided by FGF23 values + 1 (hereinafter called the Klotho/FGF23 ratio). Participants were categorized into quartiles according to Klotho/FGF23 ratio. The primary outcome was renal events, defined as the doubling of serum creatinine, 50% reduction of estimated glomerular filtration rate from the baseline values, or development of end-stage kidney disease. The secondary outcomes consisted of CV events and death. Changes in CV parameters at the time of enrollment and during follow-up according to the Klotho/FGF23 ratio were also examined.ResultsDuring the follow-up period of 64.0 ± 28.2 months, 735 (35.1%) and 273 (13.0%) subjects developed renal events and composite outcomes of CV events and death, respectively. After adjustment, the first (HR: 1.36; 95% CI: 1.08–1.72, P = 0.010) and second (HR: 1.45; 95% CI: 1.15–1.83, P = 0.002) quartiles with regard to the Klotho/FGF23 ratio showed elevated risk of renal events as compared to the fourth quartile group. There was no significant association between Klotho/FGF23 ratio and the composite outcome of CV events and death. The prevalence of left ventricular hypertrophy and vascular calcification was higher in the low Klotho/FGF23 ratio quartiles at baseline and at the fourth-year follow-up.ConclusionsLow Klotho/FGF23 ratio was significantly associated with increased renal events in the cohort of Korean predialysis CKD patients.

Fibroblast Growth Factor 23 and Cardiovascular Risk in Diabetes Patients-Cardiologists Be Aware.

Numerous clinical studies have indicated that elevated FGF23 (fibroblast growth factor 23) levels may be associated with cardiovascular (CV) mortality, especially in patients with chronic kidney disease. The purpose of this study was to examine the hypothesis that FGF23 may be a potent CV risk factor among patients with long-standing type 2 diabetes mellitus (T2DM). Research was performed utilizing patients with T2DM and regular outpatient follow-up care. Baseline characteristics determined by laboratory tests were recorded. Serum FGF23 levels were detected using a sandwich enzyme-linked immunosorbent assay. All patients underwent echocardiograms and 12-lead electrocardiograms. Data records of 102 patients (males: 57%) with a median age of 69 years (interquartile range (IQR) 66.0–74.0) were analyzed. Baseline characteristics indicated that one-third (33%) of patients suffered from ischemic heart disease (IHD), and the median time elapsed since diagnosis with T2DM was 19 years (IQR 14.0–25.0). The hemoglobin A1c, estimated glomerular filtration rate, and FGF23 values were, respectively, as follows: 6.85% (IQR 6.5–7.7), 80 mL/min/1.73 m2 (IQR 70.0–94.0), and 253.0 pg/mL (IQR 218.0–531.0). The study revealed that FGF23 was elevated in all patients, regardless of IHD status. Thus, the role of FGF23 as a CV risk factor should not be overestimated among patients with T2DM and good glycemic control.

Factors associated with 1-year changes in serum fibroblast growth factor 23 levels in pediatric patients with chronic kidney disease.

Fibroblast growth factor 23 (FGF23) levels increase as kidney function decreases and are associated with increased mortality in patients with chronic kidney disease (CKD). Inflammation has also been shown to increase FGF23 production in adults; however, this has not been validated in pediatric patients with CKD. Furthermore, previous studies on children involved a single measurement of FGF23 without a follow-up, and a few studies have examined changes in FGF23 levels. We measured the levels of serum intact FGF23, tumor necrosis factor-α (TNF-α), and interleukin-6 as parameters of inflammation and other variables related to bone metabolism at baseline and after 1year in 62 pediatric patients with CKD (stages 2-5D, 1-16years old). Factors related to changes in FGF23 levels were investigated. The median age of patients at the evaluation was 10.5years (interquartile range 6.0-14.0), and the estimated glomerular filtration rate (eGFR) was 59.0mL/min/1.73 m2 (45.1-69.3). Primary diseases included congenital anomalies of the kidney and urinary tract, ischemic kidney, and glomerulonephritis. The baseline value of FGF23 was 66.5pg/mL (48.3-96.4), and percent change in FGF23 levels after 1year was 8.5% (-29.9-74.7). The percent change in FGF23 levels showed a negative correlation with that in eGFR (P = 0.010), and a positive correlation with that in TNF-α levels (P = 0.035). A multivariate linear regression analysis identified TNF-α as an independent factor increasing FGF23 levels. An increase in TNF-α levels is associated with elevation of FGF23 levels in pediatric patients with CKD.

MO630: Association Between Inflammatory Markers and Progression of Diabetic Kidney Disease

Abstract BACKGROUND AND AIMS Diabetes mellitus is the major cause of end-stage renal disease. Patients with diabetic kidney disease (DKD) have a higher risk of mortality, mostly from cardiovascular complications. Previous studies have shown that inflammatory cytokines are involved in the pathogenesis of microvascular diabetic complications, including DKD. Standard biomarkers including serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers is necessary to detect kidney injury and predict clinically significant outcomes in diabetic patients. The aim of our study was to find relation between serum inflammatory and growths markers and CKD in patients with DT2. METHOD A total of 155 patients with DT2, aged 34–84 years [60 (60; 72)], were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor-23 (FGF-23) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). RESULTS The levels of VEGF-A, FGF-23, TNF-α, hs-CRP and Il-6 were significantly higher in diabetic patients with CKD 5 in comparison with stages 1–4. There were positive significant association between VEGF-A, FGF-23, TNF-α, hs-CRP, IL-6 and markers of renal function (creatinine, A/K). Thus VEGF-A, TNF-α and hs-CRP showed a weak and moderate correlation with creatinine, while IL-6 and FGF-23 showed a strong correlation (r = 0.70, P &amp;lt; 0.001, r = 0.71, P &amp;lt; 0.001, respectively). In addition, IL-6 significantly correlated with cystatin C (r = 0.71, P &amp;lt; 0.001). A strong negative correlation was also observed between IL-6 and eGFR (r=−0.73, P &amp;lt; 0.001). In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR (95% CI 1.890); 1.362–2.622, P &amp;lt; 0.001), IL-6 (1.527; 1.251–1.863, P &amp;lt;.001), hs-CRP (1.405; 1.231–1.602, P &amp;lt;.001). When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 which corresponds to the highest Youden's J statistic was 0.9 pmol/L. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively [AUC 0.832 ± 0.035 (95% CI 0.764–0.901), P &amp;lt; 0.001]. The cut-off value of IL-6 was 3.1 mg/mL. The sensitivity and specificity of the method were 64.3% and 73.7%, respectively [AUC 0.750 ± 0.029 (95% CI 0.694–.807), P&amp;lt;0.001]. The cut-off value of hs-CRP was 5.8 mg/L. The sensitivity and specificity of the method were 72.2% and 75.7%, respectively (AUC 0.749 ± 0.029 (95% CI 0.693–.806) P &amp;lt; 0.001). CONCLUSION Involvement of mediators of inflammation and fibrogenesis in the processes of tubulointerstitial damage in patients with diabetes and CKD, confirmed by their negative correlation with GFR and positive with creatinine and albuminuria, indicates a high risk of a decrease in GFR in patients with diabetes with an increase in IL-6 ≥3.1 mg/mL, FGF-23 ≥0.9 pmol/L and hs-CRP ≥5.8 mg/mL along with traditional risk factors.

The Correlation of Fibroblast Growth Factor 23 with Cardiac Remodeling in Essential Hypertension with Normal Renal Function

Background: Fibroblast growth factor 23 (FGF23), a glycoprotein-regulating calcium and phosphorus homeostasis, has been linked to cardiovascular diseases. We aimed to evaluate the correlation of FGF23 levels and cardiac remodeling (left atrial [LA] enlargement and left ventricular hypertrophy [LVH]) in essential hypertension (EH) with normal renal function and explore the diagnostic values of FGF23 and B-type natriuretic peptide (BNP) in cardiac remodeling. Methods and Results: We enrolled 40 healthy control subjects (group I) and 146 EH patients (group II). Plasma FGF23 concentration was measured in all subjects. In this study, FGF23 level was significantly higher in group II (660.77 [446.26, 1,001.72]) pg/mL compared with the controls (73.23 [52.92, 103.69]) pg/mL (p < 0.001). Logistic regression analysis revealed that FGF23 was independently correlated to LVH and LA enlargement. Receiver operating characteristic (ROC) curve indicated FGF23 had an optimal cutoff of 834.63 pg/mL for LVH (area under ROC curve [AUC], 0.913; 95% CI: 0.863–0.963) and 497.06 pg/mL for LA enlargement (AUC, 0.694; 95% CI: 0.612–0.768). The DeLong test was performed to compare AUCs of FGF23 and BNP, and the AUC of FGF23 (0.913) was statistically higher compared to AUC of BNP (0.661) (DeLong test: p < 0.001) in the diagnosis of LVH. Conclusion: Plasma FGF23 level elevated in EH, increased with the progress of cardiac remodeling, and was independently related to LVH and LA enlargement. The diagnostic value of FGF23 in cardiac remodeling, especially for LVH, was superior to BNP.

Weight Gain, Fibroblast Growth Factor‐23, and Vascular Function in Liver Transplant Recipients

INTRODUCTIONLiver transplant (LT) recipients experience significant weight gain and an increased risk of cardiovascular disease (CVD) after transplant. The pathophysiology of this cardiometabolic burden is not fully understood. In the general population, weight gain and increased adiposity are associated with elevated circulating levels of fibroblast growth factor‐23 (FGF‐23). Increased FGF‐23 has been linked with CVD in other disease populations. This study tested the working hypothesis that weight gain after LT is associated withincreased levels of FGF‐23, that subsequently contribute to vascular dysfunction, an established precursor of CVD.METHODSWe enrolled 21 LT patients (M/F: 9/12; Mean ± SEM, Age: 55 ± 2 yrs) and 8 age matched healthy controls (HC; M/F: 2/6; 47 ± 6 yrs). Vascular endothelial function was assessed with flow‐mediated dilation (FMD) of the brachial artery using duplex ultrasound. Aortic pressure waves were synthesized from radial artery waveforms acquired by applanation tonometry and the use of a generalized transfer function. Serum levels of FGF‐23 were assessed by enzyme linked immunosorbent assay (ELISA).RESULTSHigher body mass index (BMI) values were reported in LT patients (37 ± 1 kg/m2) compared to HC (26 ± 1 kg/m2, p = &lt;0.001). Weight gain (BMI) was positively associated with serum FGF‐23 values (r = 0.5, p = 0.01). Central systolic pressures (125 ± 3 vs. 110 ± 6 mmHg, p = 0.01) and central pulse pressures (51 ± 4 vs. 39 ± 4 mmHg, p = 0.05) were higher in LT patients compared with controls. There was no difference in endothelial function (FMD) in LT patients (4.59 ± 0.55%) compared to their HC counterparts (6.08 ± 0.48%, p = 0.12). FGF‐23 values were not associated with measures of vascular function.CONCLUSIONWeight gain is evident in LT patients and is correlated with higher serum FGF‐23 values. However, our findings do not suggest a relationship between serum levels of FGF‐23 and vascular function in LT recipients.

Plasma Fibroblast Growth Factor 23 as a Predictor for Fosinopril Therapeutic Efficacy in Pediatric Primary Hypertension.

BackgroundPlasma fibroblast growth factor 23 (FGF23) has been reported to be a predictive biomarker for therapeutic effectiveness of angiotensin‐converting enzyme inhibitors in heart failure. Higher plasma FGF23 levels have been shown in pediatric primary hypertension, but the predictive value of FGF23 for angiotensin‐converting enzyme inhibitors’ effectiveness in pediatric primary hypertension has not been documented.Methods and ResultsThis is a prospective study. An exploratory study with 139 patients was first conducted to determine the cutoff value of FGF23 for the prediction of treatment responsiveness. After receiving fosinopril for 4 weeks, of all 139 patients, 91 responded, while 48 did not respond to the treatment, and the responders had a significantly higher baseline plasma FGF23 level than nonresponders (P<0.01). Multiple regression analysis revealed a significant impact of baseline plasma FGF23 levels on fosinopril responsiveness (P<0.05). The receiver operating characteristic curve analysis showed that the plasma FGF23 predicted the effectiveness of fosinopril treatment with an area under the curve of 0.784 (95% CI, 0.704–0.863) for a sensitivity and a specificity of 67.0% and 89.6%, respectively, for a cutoff value of 62.08 RU/mL. Subsequently, another group of 40 patients were recruited for validation. The blood pressure control rate in those (n=22) with baseline plasma FGF23 >62.08 RU/mL was significantly higher than that in children (n=18) with FGF23 ≤62.08 RU/mL (P<0.05).ConclusionsPlasma FGF23 might be a valuable biomarker to guide fosinopril therapy for primary hypertension in children.

Evaluation of α-klotho, FGF-23 and Insulin Resistance in Obese Prediabetics

Aim: Prediabetes is a condition with hyperglycemia and risk of development type 2 diabetes mellitus (T2DM). The aim of this study is to determine the concentrations of blood pressure, serum lipoproteins, glucose and insulin levels as well as the concentrations of α-klotho and FGF-23 parameters. We also aim at the correlation between all these parameters in obese prediabetics and obese normoglycemics. Material methods: A total of 26 obese normoglycemic (control group) and 25 obese prediabetic individuals were included in this study. Glucose, haemoglobin A1c (HbA1c) and cholesterols levels were analyzed as part of a routine procedure in the biochemistry laboratories of our hospital using an autoanalyzer. In order to determine α-klotho and fibroblast growth factor-23 (FGF-23) levels, ELISA method was used. Result: According to the findings, a significant increase was detected in serum LDL-C, TC, HbA1c, glucose, insulin and HOMA-IR levels in the obese prediabetic group compared to the control group (p <0.05). However, serum α-klotho and FGF-23 levels were found to be significantly lower in the obese prediabetic group compared to the control group (p <0.05). α-klotho and FGF-23 values showed strong negative correlation when compared with HOMA-IR values separately (p <0.01). Conclusion: These findings suggest that α-klotho and / or FGF-23 parameters may be a marker for prediabetes. The results of our study, together with the future studies, will make a significant contribution to the literature, as prediabetes diagnostic criteria in the diabetes outpatient clinics.

Clinical performance of a novel chemiluminescent enzyme immunoassay for FGF23.

Measurement of fibroblast growth factor 23 (FGF23) has been reported to be clinically useful for the differential diagnosis of chronic hypophosphatemia. However, assays for research use only are available in Japan. Thus, the objective of this study was to examine the clinical utility of a novel and automated chemiluminescent enzyme immunoassay for the measurement of FGF23. Participants were recruited from July 2015 to January 2017 at six facilities in Japan. Thirty-eight patients with X-linked hypophosphatemic rickets (XLH 15 males, 23 females, age 0-66years), five patients with tumour-induced osteomalacia (TIO 3 males, 2 females, age 60-73years), and twenty-two patients with hypophosphatemia (11 males, 11 females, age 1-75years) caused due to other factors participated in this study. With the clinical cut-off value of FGF23 at 30.0pg/mL indicated in the Diagnostic Guideline of Rickets/Osteomalacia in Japan, the sensitivity and specificity of FGF23-related hypophosphatemic rickets/osteomalacia without vitamin D deficiency (disease group-1) were 100% and 81.8%, respectively, which distinguished it from non-FGF23-related hypophosphatemia (disease group-2). Furthermore, the diagnostic sensitivity of FGF23-related hypophosphatemia with vitamin D deficiency remained at 100%. Among the four patients with FGF23 levels ≥ 30.0pg/mL in disease group-2, two patients with relatively higher FGF23 values were suspected to have genuine FGF23-related hypophosphatemia, due to the ectopic production of FGF23 in pulmonary and prostate small cell carcinomas. The novel FGF23 assay tested in this study is useful for the differential diagnosis of hypophosphatemic rickets/osteomalacia in a clinical setting.

Diagnostic value of fibroblast growth factor 23 for abdominal aortic calcification in Indonesian hemodialysis patients.

Objective:Homeostasis of serum phosphorus and calcitriol level is regulated mainly by fibroblast growth factor 23 (FGF23). Studies show that elevated serum FGF23 level was significantly associated with aortic calcification severity, peripheral blood vessels, and a higher score of coronary artery calcification in patients undergoing hemodialysis. We did this cross-sectional study to determine the FGF23 diagnostic value for abdominal aortic calcification in Indonesian hemodialysis patients.Materials and Methods:This study included seventy-five, chronic hemodialysis patients. An enzyme-linked immunosorbent assay method was used to measure serum intact FGF23 level, and abdominal aortic calcification was detected by lateral lumbar X-ray. The diagnostic value of FGF23 was analyzed using receiver operating characteristic (ROC) curves.Results:fifty-one (68.0%) patients had abdominal aortic calcification (AAC). Serum intact FGF23 level ranged from 217 to 950 pg/mL with a median level of 328 pg/mL. The FGF23 levels in the serum of patients with AAC were significantly higher than those without AAC (P < 0.001). The best cutoff point was 277 pg/mL. The calculated area under the ROC curves was 0.959 (95% confidence interval, 0.912–1.00); sensitivity was 94.0% and specificity was 84.0% (P < 0.001).Conclusion:serum intact FGF23 level may be proposed as a proper tool for abdominal aortic calcification in Indonesian hemodialysis patients.