Serum FGF23 Levels Research Articles

Serum levels of C-terminal FGF23 (cFGF23) are associated with 1-year-mortality in patients undergoing transcatheter aortic valve replacement (TAVR)

IntroductionSerum levels of FGF23 have been associated with adverse outcomes in cardiovascular diseases in patients with and without impaired renal function. Hence, this study aimed to explore the prognostic relevance of intact FGF23 (iFGF23) and its derivate C-terminal FGF23 (cFGF23) in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function. MethodsA total of 274 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were obtained preinterventionally and analyzed for iFGF23 and cFGF23 by means of enzyme linked immunosorbent assay (ELISA). Follow-up was obtained for 12 months. ResultsSerum levels of cFGF23 and iFGF23 both correlated positively with serum creatinine and inversely with estimated glomerular filtration rate (eGFR). Cox regression analysis revealed a significant association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m², but not in patients with an eGFR <45ml/min/1.73m². A cut-off was calculated for cFGF23 (6.82 pmol/l) and patients with eGFR ≥45ml/min/1.73m² were retrospectively divided into two groups (above/below cut-off). Patients above the cut-off had a significantly worse 1-year-mortality than patients below the cut-off (33.3% vs. 19.6%; OR 2.05 (95%CI 1.03-4.07), p= 0.038). The association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m² remained statistically significant even after correction for possible confounders in a multivariate Cox regression analysis. ConclusioncFGF23 could be an individual risk factor for mortality in patients undergoing TAVR with an eGFR ≥45ml/min/1.73m².

Effect of Moderate Aerobic Exercise on Serum Levels of FGF21 and Fetuin A in Women with Type 2 Diabetes

Effect of Moderate Aerobic Exercise on Serum Levels of FGF21 and Fetuin A in Women with Type 2 Diabetes

Serum fibroblast growth factor 21 level is increased in pre-eclampsia patients: Association with blood pressure and lipid profile.

Pre-eclampsia (PE) is dangerous complication, which leads to adverse pregnancy outcomes. The study was to explore the correlation between serum level of fibroblast growth factor (FGF) 21 and PE. A total of 80 cases were involved in this study containing PE group (49 cases) and control group (31 cases, normal pregnancy). PE group was divided into early-onset PE (EOPE) and late-onset PE (LOPE). Serum level of FGF21 and biochemical parameters were measured before delivery. Maternal serum FGF21 level was higher in PE especially in EOPE than that in control groups (P < 0.05). In PE patients, serum FGF21 level was positively correlated with mean arterial pressure, diastolic blood pressure and low-density lipoprotein cholesterol (P < 0.05). Levels of FGF21, uric acid and low-density lipoprotein cholesterol were risk factors for PE. Maternal serum FGF21 level in PE particularly in EOPE was higher and was associated with blood pressure and lipid profile.

Fibroblast Growth Factor 21 Association with Renal Function Decline in Type II Diabetes Mellitus

Serum FGF21 level is strongly associated with the onset of nephropathy in T2D patients and is an independentpredictor of loss of renal function in these patient.The study aimed to evaluate the role of FGF21 in earlydetection of diabetic nephropathy in type 2 diabetes patents. The study included Eighty-eight(88) samplesdivided in to four groups, three of which included type 2 diabetes patients, according to mircal test (urinealbumin / creatinine ratio), they were classified as :22normalbuminuria , 22 microalbuminuria, and 22macroalbuminuria. The fourth group included 22 apparently healthy subjects with (matched gender andage).The mean ±SD of serum fibroblast growth factor 21 of normoalbuminuria group was (225.00±38.62),microalbuminuria group was (267.78±51.08) and macroalbuminuria group was (230.84±50.33) .Thecomparison results indicated significant increase (p?0.05) of FGF21 in microalbuminuria group in comparisonto that level in normoalbuminurea and macroalbuminuria groups. Also highly significant increase of FGF21was observed in microalbuminuria group in comparison to that level in control group. We conclude thatFGF21 may be a useful marker for early detection of nephropathy

Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity.

Background: There is a pressing need for effective and non-invasive biomarkers to track intrahepatic triglyceride (IHTG) in children at-risk for non-alcoholic fatty liver disease (NAFLD), as standard-of-care reference tools, liver biopsy and magnetic resonance imaging (MRI), are impractical to monitor the course disease.Objective: We aimed to examine the association between serum fibroblast growth factor (FGF)-21 to adiponectin ratio (FAR) and IHTG as assessed by MRI in children with obesity.Methods: Serum FGF21 and adiponectin levels and IHTG were measured at two time points (baseline, 6 months) in obese children enrolled in a clinical weight loss program. The association between percent change in FAR and IHTG at final visit was examined using a multiple linear regression model.Results: At baseline, FAR was higher in the subjects with NAFLD (n = 23, 35.8 ± 41.9 pg/ng) than without NAFLD (n = 35, 19.8 ± 13.7 pg/ng; p = 0.042). Forty-eight subjects completed both visits and were divided into IHTG loss (≥1% reduction than baseline), no change (within ±1% change), and gain (≥1% increase than baseline) groups. At 6 months, the percent change in FAR was different among the three groups (p = 0.005). Multiple linear regression showed a positive relationship between percent change in FAR and the final liver fat percent in sex and pubertal stage-similar subjects with NAFLD at baseline (slope coefficient 6.18, 95% CI 1.90–10.47, P = 0.007), but not in those without NAFLD.Conclusions: Higher value in percent increase in FAR is positively associated with higher level of IHTG percent value at 6 months in children with baseline NAFLD. FAR could be a potential biomarker to monitor the changes in IHTG in children with NAFLD.

Genome-wide association study for circulating fibroblast growth factor 21 and 23

Fibroblast growth factors (FGFs) 21 and 23 are recently identified hormones regulating metabolism of glucose, lipid, phosphate and vitamin D. Here we conducted a genome-wide association study (GWAS) for circulating FGF21 and FGF23 concentrations to identify their genetic determinants. We enrolled 5,000 participants from Taiwan Biobank for this GWAS. After excluding participants with diabetes mellitus and quality control, association of single nucleotide polymorphisms (SNPs) with log-transformed FGF21 and FGF23 serum concentrations adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for body mass index (BMI) and a third model additionally adjusted for BMI and estimated glomerular filtration rate (eGFR) were used. A total of 4,201 participants underwent GWAS analysis. rs67327215, located within RGS6 (a gene involved in fatty acid synthesis), and two other SNPs (rs12565114 and rs9520257, located between PHC2-ZSCAN20 and ARGLU1-FAM155A respectively) showed suggestive associations with serum FGF21 level (P = 6.66 × 10–7, 6.00 × 10–7 and 6.11 × 10–7 respectively). The SNPs rs17111495 and rs17843626 were significantly associated with FGF23 level, with the former near PCSK9 gene and the latter near HLA-DQA1 gene (P = 1.04 × 10–10 and 1.80 × 10–8 respectively). SNP rs2798631, located within the TGFB2 gene, was suggestively associated with serum FGF23 level (P = 4.97 × 10–7). Additional adjustment for BMI yielded similar results. For FGF23, further adjustment for eGFR had similar results. We conducted the first GWAS of circulating FGF21 levels to date. Novel candidate genetic loci associated with circulating FGF21 or FGF23 levels were found. Further replication and functional studies are needed to support our findings.

Severe Symptomatic Hypophosphataemia as a Complication of Parenteral Iron Replacement.

The carbohydrate moieties used in parenteral iron preparations are different, and may have a dose-dependent relationship with the development of hypophosphataemia.The mechanism by which hypophosphataemia occurs after parenteral iron replacement is related to increased serum levels of FGF23, which increases renal phosphate wasting.The serum phosphate levels of patients receiving parenteral iron replacement (especially ferric carboxymaltose or iron polymaltose) should be routinely monitored for hypophosphataemia, which is an under-diagnosed complication.

Low Serum Levels of Fibroblast Growth Factor 2 in Gunn Rats: A Hyperbilirubinemia Animal Model of Schizophrenic Symptoms.

Fibroblast Growth Factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and prodifferentiation of neurons. Because alterations in FGF2 levels are suggested to contribute to the pathogenesis of schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats, serum levels were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of Unconjugated Bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 in terms of serum levels in all the rats studied. Since it is known that FGF2 regulates dopaminergic neurons and have antineuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which imbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.

Fibroblast Growth Factor Receptor 4 Deficiency Mediates Airway Inflammation in the Adult Healthy Lung?

Fibroblast growth factor receptor (FGFR) 4 has been shown to mediate pro-inflammatory signaling in the liver and airway epithelium in chronic obstructive pulmonary disease. In past reports, FGFR4 knockout (Fgfr4−/−) mice did not show any lung phenotype developmentally or at birth, unless FGFR3 deficiency was present simultaneously. Therefore, we wanted to know whether the loss of FGFR4 had any effect on the adult murine lung. Our results indicate that adult Fgfr4−/− mice demonstrate a lung phenotype consisting of widened airway spaces, increased airway inflammation, bronchial obstruction, and right ventricular hypertrophy consistent with emphysema. Despite downregulation of FGF23 serum levels, interleukin (IL) 1β and IL-6 in the Fgfr4−/− lung, and abrogation of p38 signaling, primary murine Fgfr4−/− airway cells showed increased expression of IL-1β and augmented secretion of IL-6, which correlated with decreased airway surface liquid depth as assessed by micro-optical coherence tomography. These findings were paralleled by increased ERK phosphorylation in Fgfr4−/− airway cells when compared with their control wild-type cells. Analysis of a murine model with constitutive activation of FGFR4 showed attenuation of pro-inflammatory mediators in the lung and airway epithelium. In conclusion, we are the first to show an inflammatory and obstructive airway phenotype in the adult healthy murine Fgfr4−/− lung, which might be due to the upregulation of ERK phosphorylation in the Fgfr4−/− airway epithelium.

Serum β-Klotho concentrations are increased in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a significant cause of menstrual disorders and infertility in women. The aim of this study was to evaluate the levels of Klotho expression in women with polycystic ovary syndrome. The study involved 67 patients with PCOS, as well as 18 controls. Serum levels of FGF19, FGF21 and β-Klotho were measured by ELISA technique. The blood samples were obtained between days 2 and 7 of menstrual cycle.The concentrations of β-Klotho, FGF19 and FGF21 were significantly increased in patients with PCOS; and appear to be statistically significant predictors of PCOS incidence.FGF19 (p = 0.031, OR = 1.01), exact β-Klotho levels (p = 0.022, OR = 1.01) and β-Klotho beyond the reference range (p = 0.008, OR = 4.66) were the most strongly correlated with the diagnosis of PCOS.In conclusion, FGF19, FGF21 and β-Klotho are increased in PCOS, and elevated β-Klotho concentration may become an useful diagnostic test for this disease. However, additional studies are required to further substantiate this observation.

Low serum Klotho level as a predictor of calcification of the heart and blood vessels in patients with CKD stages 2-5D

The study included 131 patients with chronic kidney disease 25D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years. According to the Spearman correlation analysis, the percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level 632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m2 with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.04637.962; p0.001). The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.

Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH)

X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized.We analyzed transiliac bone biopsies from four adult patients, two of them severely affected due to no diagnosis and no treatment until adulthood. We used light microscopy, qBEI and FTIRI to study histology, histomorphometry, bone mineralization density distribution, properties of the organic matrix and size of hypomineralized periosteocytic lesions.Non-treatment resulted in severe osteomalacia, twice the amount of mineralized trabecular volume, multiple osteon-like perforations, continuity of lamellae from mineralized to unmineralized areas and distinctive patches of woven bone. Periosteocytic lesions were larger than in treated patients. The latter had nearly normal osteoid thicknesses, although surface was still elevated.The median calcium content of the matrix was always within normal range, although the percentage of lowly mineralized bone areas was highly increased in non-treated patients, resulting in a marked heterogeneity in mineralization.Divalent collagen cross-links were evident independently of the mineral content of the matrix. Broad osteoid seams lacked measurable pyridinoline, a mature trivalent cross-link and exhibited considerable acidic lipid content, typically found in matrix vesicles.Based on our results, we propose a model that possibly integrates the relationship between the observed mineralization disturbances, FGF23 secretion and the known osteopontin accumulation in XLH.

Mediation of the relationship between proteinuria and serum phosphate: Insight from the KNOW-CKD study.

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.

Differential effects of protein intake versus intake of a defined oligopeptide on FGF-21 in obese human subjects invivo.

FGF-21 is described as a powerful metabolic regulator with beneficial effects including glucose-lowering and improvement of insulin sensitivity without hypoglycaemia. On the other hand, FGF-21 is activated when muscle and other tissues are stressed by external effects or internal cellular pathogens that lead to shortcomings in metabolic balance. Previous results suggested that FGF-21 could be a promising target to develop future metabolic therapeutics. The present study was performed to gain deeper insight into the regulation of FGF-21 by protein metabolism in obese human subjects. FGF-21 serum concentrations were measured in a cohort of n=246 obese humans±type 2 diabetes mellitus (T2DM) (median age 53.0 [46.0; 60.0] years and BMI 40.43 [35.11; 47.24] kg/m2) and related to the nutritional protein intake. In addition, the effect of a novel oligopeptide purified from a β-casein hydrolysate on FGF-21 was examined invitro in liver cells and invivo in a human intervention study with the main focus on metabolic inflammation including 40 mainly obese subjects (mean age 41.08±9.76 years, mean BMI 38.29±9.4kg/m2) in a randomized 20 weeks double-blind cross-over design. In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. Furthermore, relative methionine intake was inversely related to FGF-21. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a β-casein oligopeptide increased FGF-21 expression invitro. This stimulatory effect was also present invivo, since in the clinical intervention study treatment of obese subjects with the β-casein oligopeptide for 8 weeks significantly increased FGF-21 serum levels from W0=23.86pg/mL to W8=30.54pg/mL (p<0.001), while no increase was found for placebo. While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and well characterised oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake.

Fibroblast Growth Factor 21 is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Atherosclerotic Cardiovascular Events.

BackgroundFGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF21 could predict incident atherosclerotic cardiovascular disease in a 7‐year prospective cohort.Methods and ResultsBaseline serum FGF21 was measured in a cross‐sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population‐based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross‐sectional study, FGF21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis (P<0.01). The association remained significant after adjusting for demographic and traditional cardiovascular risk factors. In the prospective cohort, 80 patients developed atherosclerotic cardiovascular disease during follow‐up. Baseline FGF21 was significantly higher in those who developed ischemic heart disease or cerebral infarction than in those who did not. Using a cutoff serum concentration of 232.0 pg/mL, elevated baseline FGF21 independently predicted incident total atherosclerotic cardiovascular disease events, ischemic heart disease, and cerebral infarction in a nondiabetic population (all P<0.05), and significantly improved the discriminatory and reclassifying abilities of our prediction model after adjustment for established cardiovascular risk factors.ConclusionsThis study provides the first evidence that FGF21 levels are elevated in patients without nonalcoholic fatty liver disease with subclinical atherosclerosis. Baseline FGF21 is an independent predictor of atherosclerotic cardiovascular disease and represents a novel biomarker for primary prevention in the general population.

P0875INFLUENCE OF CHRONIC KIDNEY DISEASE AND LEFT VENTRICULAR HYPERTROPHY ON CHANGE IN FGF23 AND RENIN-ANGIOTENSIN-ALDOSTERONE-SYSTEM

Abstract Background and Aims Left ventricular hypertrophy (LVH) is a clinically important risk factor for mortality and often observed in patients with chronic kidney disease (CKD). Serum FGF23 levels are elevated in CKD patients, and the relationship between elevated FGF23 and LVH has been reported in the previous studies. However, whether elevated FGF23 is a cause or result of LVH and whether FGF23 directly or indirectly affects LVH remain unclear. Therefore, we investigated changes in heart weight, CKD-mineral and bone disorder (MBD) parameters, including FGF23, and renin-angiotensin-aldosterone system (RAAS) related-factors in the setting of LVH and CKD using a mouse model. Method In the present study, twenty-four C57BL/6J mice were used and divided into 4 groups; control group (N=6), CKD group (N=6), LVH group (N=6), and LVH+CKD group (N=6). The mice in the CKD group underwent left 2/3 nephrectomy at 11 weeks of age and right nephrectomy at 12 weeks of age. Those in the LVH group underwent transverse aortic constriction (TAC) at 10 weeks of age. Those in the LVH+CKD group, TAC at 10 weeks of age, and left 2/3 nephrectomy at 11 weeks of age, and right nephrectomy at 12 weeks of age were performed. At 16 weeks of age, echocardiography was performed for all the mice, and they were sacrificed for blood and urine analysis, histopathological analysis and evaluating mRNA expressions of CKD-MBD- and RAAS-related factors in the heart. Results The systolic blood pressure was significantly higher in the LVH+CKD group and the CKD group than in the control group. The heart weight/body weight ratio in the LVH+CKD group was the highest, and that in the LVH was higher than that in the CKD group. Although serum creatinine and phosphate levels increased in CKD condition, those were comparable between the CKD and LVH+CKD groups. The urinary albumin excretion also increased in the CKD and LVH+CKD groups compared to the LVH and control groups. Serum FGF23 levels increased in the LVH and CKD group compared to the control group, and those in the LVH+CKD group were the highest among all the study groups. The cardiac mRNA expressions of FGF23, angiotensinogen (ANG), angiotensin type 1 receptor (AT1R), and angiotensin-converting enzyme (ACE) were also increased by induction of LVH and CKD, and those in the LVH+CKD group significantly increased compared to other groups. Heart weight/body weight ratio was significantly correlated with serum FGF23 levels and mRNA expression of FGF23, ANG, AT1R, ACE. In addition, significant correlations of serum FGF23 levels and cardiac mRNA expression of FGF23 with cardiac mRNA expressions of RAAS-related factors were observed. Conclusion Our results suggest that serum FGF23 levels and cardiac mRNA expression of FGF23 increase with the development of LVH and CKD and the changes is possibly enhanced through the colocalized activation of RAAS.

P0667FIBROBLAST GROWTH FACTOR 21 PROMOTES AND PREDICTS VASCULAR CALCIFICATION IN HAEMODIALYSIS PATIENTS

Abstract Background and Aims Cardiovascular disease (CVD) is the leading cause of death in hemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and strongly associated with CVD events and mortality in HD patients. This study aimed to achieve 4 objectives using a population-based retrospective cohort of HD patients: (1)quantify the correlation between FGF21 and VC; (2)determine whether FGF21 is a novel risk factor for VC; (3)examine the predictive effect of FGF21 on VC; (4)explore the underlying mechanism of FGF21 in promoting VC, especially focused on the EndMT process, in cultured human aortic endothelial cells (HAECs). Method 802 HD patients were screened, at last 388 HD patients were eligible in the study. Serum FGF21 levels were assessed by ELISA kits. Chest radiographies of HD patients taken by multislice computed tomography were used to measure TACS. HD patients were divided into two groups : low TACS group (&amp;lt; median of TACS) and high TACS group (≧median of TACS). Univariate analyses were performed to compare the differences between two groups. Categorical data were compared using the Chi-square test. Stepwise multivariate linear regression analyses were employed to evaluate variables independently associated with TACS. The ROC curves were performed to calculate the AUC and compare the prognostic value of every independently associated factor or united factor to VC. Additionally HAECs was pretreated with FGF21 in the presence or absence of PTH. The formation of calcium deposits was analysed by Alizarin Red staining (ARS). PCR for the measurement of mRNA of CD31, RUNX2 and FSP1 to evaluate endothelial-to-mesenchymal transition (EndMT) of HAECs. Results Prevalence of VC was 70.1% in this study. Serum FGF21 levels of HD patients were 11-fold higher than controls (median 217 vs. 20 pg/ml). HD patients in the high TACS group had older age, higher FGF21, higher FGF23, longer dialysis vintage, higher incidence of hypertension and higher incidence of CVD (all P&amp;lt;0.05) compared with those in the low TACS group. Ln (FGF21) was positively related with Ln (TACs+1) (r=0.295). ROC curves showed that the AUC of FGF21 for predicting TAC was 0.63 (P&amp;lt;0.01), while FGF21 combined with other independent associated factors like age, calcium and PTH, the AUC markedly increased (AUC=0.84) with optimal sensitivity (82%) and specificity (71%). ARS showed that calcium deposition was observed in cultured HAECs stimulated by PTH alone and even aggravated by PTH+FGF21; however, no calcium deposition was observed in HAECs stimulated by FGF21 alone. Compared with the control, reduced expression of CD31(endothelial cell marker) mRNA in parallel with increased expression of RUNX2(osteoblast marker) mRNA and FSP1(mesenchymal cell marker) mRNA was observed in HAECs stimulated by PTH. However, FGF21 alone had no significant effect on the EndMT process. Notably, stimulation of PTH+FGF21 in HAECs aggravated the effect of PTH alone on EndMT. Conclusion This study is the first to show that serum FGF21 levels were significantly and independently correlated with VC in HD patients. Furthermore, FGF21 combined with PTH, calcium and age can significantly predict VC in HD patients. Additionally FGF21 aggravated the effect of PTH on calcium deposition and EndMT in HAECs. Taken together, our in vivo and in vitro results indicated that FGF21 was a novel predictor and promoter of VC in HD patients.

1868-P: Implementation of Dietary Methionine Restriction Using Casein after Selective, Oxidative Deletion of Methionine

Restriction of methionine in rodent diets increases energy expenditure, limits weight gain, improves insulin sensitivity, and reduces hepatic and circulating lipids. Dietary methionine restriction (MR) is implemented using diets formulated from elemental amino acids (AA) that reduce methionine content to restricted levels of ∼0.17%. However, translational implementation of dietary MR with elemental AA-based diets is confounded by poor palatability. To solve this problem and restrict methionine using intact proteins, casein was subjected to mild oxidation to selectively reduce methionine. Diets were then formulated using oxidized casein, adding back methionine to produce a final concentration of 0.17%. The biological efficacy of dietary MR using the oxidized casein diet was compared to the standard elemental MR diet. Thirty-two, 5-week old male C57BL/6J mice were divided into two groups of 16, with one group receiving the Elemental Control (El Con) diet and the other receiving the Casein Control (Cas Con) diet for 10 days. Thereafter, 8 mice continued on the El Con diet and 8 mice were switched to the Elemental MR (El MR) diet. In similar fashion, 8 mice continued on the Cas Con diet and 8 mice were switched to the Oxidized Casein (Ox Cas) MR diet. Over the subsequent 8 weeks, the behavioral, metabolic, and endocrine responses to the 4 diets were assessed to evaluate the relative efficacy of the 2 approaches to restricting dietary methionine. The El MR diet produced the expected reductions in body weight, fat mass accumulation, fasting insulin, and hepatic and circulating triglycerides, while increasing energy expenditure, serum FGF-21 levels, and weight-specific food consumption. The Ox Cas MR diet produced increases and decreases in each of these variables that paralleled the effects of the El MR diet. Collectively, these findings demonstrate that dietary MR can be effectively implemented using casein after selective oxidative reduction of methionine. Disclosure H. Fang: None. K.P. Stone: None. L. Forney: None. L.C. Sims: None. T.W. Gettys: None. Funding Pennington Foundation

THE RELATIONSHIP BETWEEN SERUM FGF-23 CONCENTRATION AND CLINICAL AND SUBCLINICAL FACTORS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Objective: To evaluate the relationship between serum FGF-23 levels and other factors affecting bone mineral disorders in chronic kidney disease. Method: Cross-sectional study, describe and analyze of the relationship between FGF-23 and biochemical parameters, clinical characteristics of 149 patients with chronic kidney disease. Results: For conservative group, FGF-23 level correlated positively with level of urea, creatinine and inversely correlated with glomerular filtration rate (GFR); the level of urea, creatinine and GFR are the three most influential factors on FGF-23 level, the changes in level of urea, creatinine and GFR explain 30.6% and 29.5% and 11.2% respectively of change in FGF-23 level with p &lt; 0.05. For hemodialysisgroup, there is a positive correlation between the level of FGF-23 and the level of total calcium, Phosphorus and calcium-phosphorus accumulation; Total calcium, Ca x P level are the twoo most influential factors on the level of FGF-23, total calcium changes, Ca x P explain 29.7% and 18.8% respectively of change in FGF-23 level with p &lt; 0.05. Conclusion: There is a strong correlation between FGF-23 levels and factors affecting bone mineral disorders in patients with chronic kidney disease. Key words: chronic kidney disease, fibroblast growth factor 23

P0025BARIATRIC SURGERY MAY REDUCE UPREGULATED EXPRESSION OF FIBROBLAST GROWTH FACTOR 21 AND ANGIOTENSIN-CONVERTING ENZYME 2 IN OBESE PATIENTS

Abstract Background and Aims Recent studies showed that the fibroblast growth factor 21 (FGF21) and angiotensin-converting enzyme 2 (ACE2)/Angiotensin 1-7 (Ang (1-7))/MAS axis of the renin-angiotensin system counteract to the negative role of Ang II in various disease. In this study, we examed FGF21 and ACE2/Ang (1-7) in obesity and its change after bariatric surgery. Method We prospectively enrolled obese patient who performed bariatric surgery and age-sex matched healthy volunteers (HV) (n=12 each). We obtained their clinical information and serum samples. Serum FGF-21, Ang II, ACE2, and Ang (1-7) levels were measured by enzyme-linked immunosorbent assay kits. We measured also FGF-21, Ang II, ACE2, and Ang (1-7) 6 months after bariatric surgery in obese patients (n=12). Results FGF21, Ang II, and ACE2 levels were significantly higher in obese patients compared with HV (p= 0.045, &amp;lt; 0.001, and 0.020, respectively). FGF21, Ang II, and ACE2 levels were significantly decreased after bariatric surgery (p = 0.002, 0.005, and 0.023, respectively). There was no significant difference in Ang (1-7) levels between obese patients and HV (p = 0.887) (Figure 1). Although Ang (1-7) levels did not change after bariatric surgery (p = 0.480), changes in Ang (1-7) levels were positively correlated with changes in body mass index (BMI) (R2 = 0.580, p = 0.048) (Figure 2). Conclusion FGF21 and ACE2 were upregulated in obese patients and they are reduced after bariatric surgery. A decrease in BMI after bariatric surgery could lead to decrease in Ang (1-7).