Serum FGF23 Levels Research Articles

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 < 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 < 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, < 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).

P0754FGF23 AND URINARY PHOSPHATE EXCRETION FOR ESTIMATION OF NEPHRON NUMBER: DIFFERENCES BETWEEN CHRONIC KIDNEY FAILURE AND KIDNEY TRANSPLANTATION

Abstract Background and Aims Assuming that FGF23 levels correlate with phosphate excretion per nephron, nephron number can be estimated by measuring FGF23 levels and urinary phosphate excretion (FEP). Kuro-O proposed that the ratio of FEP to serum FGF23 levels should correlate with nephron number and is defined as the Nephron Index (NI). The aim of the study is calculating NI as nephron number estimation in patients affected by various degree of chronic kidney disease, both transplanted and not. Method In 147 CRF patients kidney function, mineral metabolism biomarkers and NI were evaluated. Nephron Index was calculated following Kuro-o’s equation (kuro-o 2019): NI=FEP·Ps·eGFRFGF23 Observed patients were divided into two groups: patients with CKD (noTX) and transplanted ones (TX). Results noTX group was made up of 67 patients (40 males and 27 females) affected by CKD stages from G1 to G5. TX group was composed by 80 patient (49 males and 31 females) with various degree of CKD (G1T-G4T) showing mean graft age of 83,2 ± 54,8 months (range: 10,3-268,0). The two groups differed for age (mean age 59 ± 15,6 years in CKD, 55± 10,3years in TX). Mean eGFR did not differ between TX and noTX but NI was higher in TX since FEP was higher despite lower FGF23 levels in TX. The difference in FGF23 levels does not appear to depend on Klotho and PTH whose serum levels were no different between Tx and noTx. (Table1). As far as correlations are concerned, NI correlated with eGFR, FGF23, PTH and 1,25D in both group, while NI correlated with FEP only in the TX group. It's interesting that no correlation existed between FGF23 and sP, FEP, eGFR and sKlotho in TX differently from noTX (Table2). Discussion. NI could not be properly defined as nephron number estimation in TX pts. However it may represent higher function of residual nephrons, since higher FEP did not correlate to FGF23 and could be determined by compensatory hyperfiltration (increased single nephron GFR) in transplanted patients. Conclusion After kidney transplantation, high NI value could have a functional meaning rather than represent residual number of nephrons.

P1680MINERAL METABOLISM CHANGES AFTER RENAL TRANSPLANTATION

Abstract Background and Aims Successful renal transplant restores many physiologic abnormalities, including improvement of chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome, and modifications of bone-related molecules in disease and health can help to understand pathophysiology of this syndrome. The aim of this study was to analyse the evolution of some of the new CKD-MBD players [alpha-klotho, fibroblast grow factor (FGF) 23, sclerostin] pre and post transplantation and the associations between those and the usual markers of the CKD-MBD disease [parathyroid hormone (PTH), bone alkaline phosphatase (bAP), calcitonin, vitamin D (vitD), phosphorus (Pi), Calcium (Ca) and Magnesium (Mg)] pre and post transplant. We also looked at the differences between values in the two time-points (delta). Method We performed a prospective cohort study of a consecutive sample of de novo single renal transplanted patients in our unit. At inclusion, demographic, clinical and transplant-related data were collected, X-ray of the pelvis and hands (for Adragão score) and echocardiographic findings were recorded. All patients were submitted to a bone biopsy and laboratorial evaluation at baseline (time 0). Patients were followed for 12 months (time 1), after which performed laboratorial evaluation, a second bone biopsy, echocardiogram, X-ray of pelvis and hands, bone densitometry and non-contrast cardiac CT (Agatston score). Continuous variables are presented as medians and categorical variables as frequencies. Associations between variables were performed using Wilcoxon matched-pairs test and Spearman correlation test. STATA software was used and p < 0.05 was considered statistically significant. Results We recruited 85 patients from 1st October 2015 to 1st March 2018. At the end of 12 months, 6 patients refuse to perform the 2nd evaluation, 5 had primary non-function of the kidney graft, 1 had no sample on bone biopsy in time 0 and 4 patients died. We performed a 2nd evaluation in 69 patients and included those in this study. Mean age 50.2±12.4 years, 48 men, 53 caucasian (78.8%), median BMI 24.5 (22.7 – 27.8), median dialysis vintage 55 (42 – 84). We observe a significant reduction on phosphorus (delta: -1.1 mg/dl), magnesium (delta: -0.5 mg/dl), PTH (delta: -297.7 pg/ml), Calcitonin (delta: -0.9 ng/L), sclerostin (delta: -1.1 ng/ml), bone alkaline phosphatase (delta: -11.5 U/L) and FGF23 (delta: -1656.5 RU/ml). Both calcium (delta: 0.7 mg/dl) and alpha-klotho (delta: 265.7 pg/ml) serum levels increase, with no significant changes in vitamin D levels. With restoring renal health (time 1) and comparing with time 0, PTH maintain the negative correlation with sclerostin (p=0.02) and the positive correlation with FGF23 (p=0.0002) as in time 0; modify the correlation with Pi, becoming a negative correlation instead of positive (p=0.001) and gain new correlations with Ca (p=0.001) and vitamin D levels (p=0.03). Also, PTH correlated with the delta FGF23 (rho=-0.4, p=0.003) and sclerostin correlated with delta PTH (p=0.01). FGF23 didn’t associate with delta PTH, neither PTH associated with delta sclerostin. FGF23 didn’t reveal statistical association with Pi or Ca levels after transplant, contrasting with positive associations in pre transplant (p=0.002, p<0.0001). On the contrary, sclerostin developed a new correlation with Pi (p=0.0004) and a negative correlation with Ca (p=0.01). We didn’t find correlations between these molecules and alpha-klotho. Conclusion In conclusion, it seems that sclerostin influences PTH levels and that PTH is the stimulus for the increase or decrease of FGF23 serum levels (as we found a positive association between those two molecules in both time-points and a negative association between PTH and the difference of FGF23 pre and post transplant). Levels of Ca and Pi seemed to be directly influenced by the level of PTH in post transplant, and those minerals seemed to be key factors for sclerostin secretion.

High Serum Fibroblast Growth Factor 23 Level Is Associated With Metabolic Syndrome in Kidney Transplantation Patients

BackgroundFibroblast growth factor 23 (FGF23), an important regulator of phosphate and vitamin D metabolism, has also been suggested to perform metabolic functions. This retrospective study evaluated the relationship between metabolic syndrome (MetS) and fasting FGF23 levels in patients undergoing kidney transplantation (KT). MethodsSerum carboxyl-terminal FGF23 levels were measured in fasting blood samples of 74 KT patients using a commercially available enzyme-linked immunosorbent assay. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. ResultsTwenty-four KT patients (32.4%) had MetS. Hypertension (P = .008); diabetes (P = .002), body weight (P < .001); body mass index (P < .001); waist circumference (P < .004); body fat mass (P < .001); systolic blood pressure (P = .008); and levels of triglycerides (P = .003), blood urea nitrogen (P = .007), and insulin (P = .004); homeostasis model assessment of insulin resistance (P = .001); and FGF23 (P = .002) were higher, whereas high-density lipoprotein cholesterol (P = .049) levels were lower in KT patients with MetS. Multivariable logistic regression analysis including significant variables revealed that FGF23 (odds ratio 1.030, 95% confidence interval [CI] 1.000-1.060, P = .048) was an independent predictor of MetS in KT patients. The area under the receiver operating characteristic curve to evaluate the ability of serum FGF23 in discriminating KT patients with MetS was 0.727 (95% CI 0.611-0.824, P = .0005). ConclusionThese results revealed that a high serum FGF23 level was positively associated with MetS in KT patients.

Interaction between serum FGF-23 and PTH in renal phosphate excretion, a case-control study in hypoparathyroid patients

Backgroundphosphate homeostasis is mediated through complex counter regulatory feed-back balance between parathyroid hormone, FGF-23 and 1,25(OH)2D. Both parathyroid hormone and FGF-23 regulate proximal tubular phosphate excretion through signaling on sodium- phosphate cotransporters IIa and IIc. However, the interaction between these hormones on phosphate excretion is not clearly understood. We performed the present study to evaluate whether the existence of sufficient parathyroid hormone is necessary for full phosphaturic function of FGF-23 or not.MethodsIn this case-control study, 19 patients with hypoparathyroidism and their age- and gender-matched normal population were enrolled. Serum calcium, phosphate, alkaline phosphatase,parathyroid hormone, FGF-23, 25(OH)D, 1,25(OH)2D and Fractional excretion of phosphorous were assessed and compared between the two groups, using SPSS software.ResultsThe mean serum calcium and parathyroid hormone level was significantly lower in hypoparathyroid patients in comparison with the control group (P < 0.001 and P < 0.001, respectively). We found high serum level of phosphate and FGF-23 in hypoparathyroid patients compared to the control group (P < 0.001 and P < 0.001, respectively). However, there was no significant difference in Fractional excretion of phosphorous or 1,25OH2D level between the two groups. There was a positive correlation between serum FGF-23 and Fractional excretion of phosphorous just in the normal individuals (P < 0.001, r = 0.79).ConclusionsAlthough the FGF-23 is a main regulator of urinary phosphate excretion but the existence of sufficient parathyroid hormone is necessary for the full phosphaturic effect of FGF-23.

MON-LB116 FGF-21 Is A Reliable Marker Of Insulin Resistance Before The Occurrence Of Glucose Intolerance

Background and aims: Fibroblast growth factor (FGF)-21 is a polypeptide that results in metabolic rearrangement mostly related to glucose and lipid metabolism. Serum FGF-21 level is elevated in obesity and in type 2 diabetes. The goal of this study is to evaluate the relationship between FGF-21 and peripheral insulin resistance in a wide range of baseline BMI and glucose metabolism status. Materials and methods: seventy one participants reported to the clinical research center in a fasting state twice. BMI and fat mass were calculated. Glucose metabolism was determined by fasting glucose, hemoglobin A1c and OGTT. Serum lipids panel was measured. Peripheral insulin resistance was determined using the hyperinsulinemic euglycemic clamp study. FGF-21 level was measured using enzyme-linked immunosorbent assay before and after clamp study. Study was approved by university institutional review board. Results: Of 71 participants, 48 were obese and 23 were lean. Normal glucose metabolism was documented in 43 individuals. Serum FGF-21 was significantly elevated in insulin resistant compared to insulin sensitive subgroups (0.28 ng/ml ± 0.136 vs. 0.14 ng/ml ± 0.112. p < 0.001). Despite the fact that FGF-21 is elevated in all obese population, the level was significantly higher in the insulin resistant obese subgroup compared to the insulin sensitive obese one (0.30 ng/ml ± 0.167 vs. 0.17 ng/ml ± 0.126. P =0.003). Furthermore, significantly higher FGF-21 level was also found in lean insulin resistant compared to lean insulin sensitive subgroups (0.18 ng/ml ± 0.106 vs. 0.09 ng/ml ± 0.061, p = 0.04]. Adjustment to preexisting impaired glucose tolerance did not affect the correlation between FGF-21 level and insulin resistance which remained statically significant in the seemingly healthy obese and lean subgroups. Conclusion: Serum FGF-21 level strongly correlates to peripheral insulin resistance in both obese and lean population. Nonetheless, FGF-21 level rises way before glucose metabolism abnormality can be detected. Our study suggests a cutoff level for each subgroup which may enable clinicians to risk-stratify patients and allow for early intervention.

Nephrectomy Does not Exacerbate Cancellous Bone loss in Thalassemic Mice

Patients with β-thalassemia have an increased risk of developing chronic kidney disease which is associated with osteoporosis and periodontitis. The purpose of this study was to evaluate mandibular and femoral bone change in heterozygous β-globin knockout (BKO) mice following 5/6 nephrectomy (Nx). Female and male BKO mouse blood smears demonstrated microcytic hypochromic anemia. Serum urea nitrogen, creatinine, calcium, and phosphorus levels were not changed in BKO mice. Nx increased the serum levels of urea nitrogen in both wild type (WT) and BKO mice and the level was much higher in BKO males. Serum level of creatinine was increased in Nx WT but not BKO mice. However, serum calcium and phosphorus levels were not altered. Nx induced comparable renal fibrosis in BKO mice and WT controls. Bone loss was observed in mandibular cancellous bone but not cortical bone of both male and female BKO mice. Nx decreased cancellous bone volume and cortical thickness in WT. Interestingly, BKO mice were resistant to Nx-induced cancellous bone loss. However, cortical thickness and cortical bone mineral density were reduced in Nx male BKO mice. Nx increased mRNA levels of type I collagen, Osx and Trap in WT but not BKO mice. Similarly, Nx reduced cancellous bone volume in femurs and increased osteoblast number and osteoclast number in WT not BKO mice. Serum FGF23 and erythropoietin levels were markedly increased in BKO mice. Nx decreased serum erythropoietin but not FGF23 levels. Since WT treated with erythropoietin exhibited a significant reduction in cancellous bone volume, it was possible that lower level of erythropoietin in Nx BKO mice prevented the Nx-induced cancellous bone loss.

IFN-γ control of metabolic stress response during T. gondii infection

Abstract IFN-γ is essential for host resistance against Toxoplasma gondii infection; however, overproduction of IFN-γ systemically results in increased host morbidity. During acute infection, mice lose weight due to anorexia and hypermetabolism and exhibit high levels of circulating IFN-γ. We wish to understand the role of IFN-γ in the host stress response during infection. We focused on two peptide stress hormones: GDF15 and FGF21. Growth differentiation factor 15, a member of the TGF-β family, is an anorexic agent while fibroblast growth factor 21 is a hormone that upregulates energy expenditure. Indeed, we observed increased levels of serum GDF15 and FGF21 during acute infection preceding weight loss. To investigate the contribution of IFN-γ in the regulation of GDF15 and FGF21, we transiently neutralized IFN-γ in T. gondii infected mice. We observed a decrease in serum GDF15 and FGF21 levels following IFN-γ blockade. Moreover, IFN-γ neutralization not only prevented further weight loss but also led to weight gain. However, there was no difference between control and treated mice in the tissue levels of GDF15. Altogether, these data suggest that IFN-γ contributes to the sickness response during infection by regulating the systemic levels of GDF15 and FGF21. Ongoing studies are focused on the role of IFN-γ in promoting the maturation and release to the circulation of these metabolism-regulating stress hormones during infection.

Baseline angiopoietin-2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma.

BackgroundSorafenib and lenvatinib are first‐line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear.MethodsWe identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2–3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long‐SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated.ResultsOverall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib.ConclusionThis study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.

Association of Serum Fibroblast Growth Factor 23 Levels with the Presence and Severity of Hepatic Steatosis Is Independent of Sleep Duration in Patients with Diabetes.

PurposeFibroblast growth factor (FGF) 23 is currently recognized to be involved in the occurrence and development of metabolic diseases. The present study aimed to investigate the association between serum FGF23 levels and hepatic steatosis, as well as the influence of sleep duration.Patients and MethodsThe present study population was selected from patients with diagnosed diabetes hospitalized during February 2018 to April 2019. Serum FGF23 levels were assessed by two-side sandwich enzyme-linked immunosorbent assay. The presence and severity of hepatic steatosis were determined by controlled attenuation parameter (CAP). Hepatic steatosis was determined as CAP≥302 dB/m.ResultsSerum FGF23 levels were significantly higher in individuals with hepatic steatosis than in those without hepatic steatosis (P=0.004). The present study population was divided into Q1–Q4 according to serum FGF23 quartiles. The risks of hepatic steatosis were increased more than 3 folds in Q2–Q4 (all P<0.01) compared to Q1. CAP showed an uptrend from Q1 to Q4 (P=0.005), even after adjustment for gender and age (P=0.001). Multivariate variance analyses showed significant differences in CAP among Q1–Q4 (P=0.008) and between individuals with short and long sleep duration (P=0.023), which were independent of each other. Serum FGF23 levels were positively associated with CAP independent of gender, age, total metabolic traits, and sleep duration (P=0.042).ConclusionSerum FGF23 levels were independently and positively associated with the severity of hepatic steatosis. The associations of serum FGF23 levels and sleep duration with hepatic steatosis were independent of each other.

STUDY ON SERUM FGF-23 CONCENTRATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Objective: To determine the serum FGF-23 levels in patients with chronic kidney disease (CKD) receiving conservative treatment and hemodialysis. Method: Cross-sectional study, describing serum FGF-23 concentration and some other biochemical parameters of 149 patients with chronic kidney disease at Hue Central Hospital, compared with a control group of 64 people who were not affected by CKD. Results: The concentration of FGF-23 in the control group, conservative treatment and hemodialysis group were 32.53 ± 9.803 pg/ml, 333.01 ± 243.02717 pg/ml, 717.66 ± 357.360 pg/ml, respectively, there were statistically significant differences (p &lt; 0.05). The concentration of FGF-23, PTH, total Calcium, phosphorus, Calcium x phosphorus accumulation increased with increasing renal failure (p &lt; 0.05). The concentration of Vitamin D and calcium ion decrease when renal failure level increases (p &lt; 0.05). FGF-23 had a better predictive value of the increasing total blood calcium level than PTH. FGF-23, PTH levels were all predictive of increasing blood phosphorus level, but FGF-23 was more valuable. Concentrations of FGF-23 and PTH had predictive values of the increasing Calcium x phosphorus accumulation, but FGF-23 was more valuable. The concentration of FGF-23 had predictive value of the increasing PTH concentration with the area under the curve by 0.765 (p &lt; 0.05). Conclusion: The concentration of FGF-23 significantly increased in patients with chronic kidney disease, and is worth predicting changes in factors related to mineral metabolism such as Calcium, Phosphorus, PTH Key words: hronic kidney disease, Fibroblast growth factor 23, Parathyroid hormone, Renal osteodystrophy, Calcium phosphate product

Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC.

OBJECTIVES:The precipitous increase in nonalcoholic steatohepatitis (NASH) is accompanied by a dramatic increase in the incidence of NASH-related hepatocellular carcinoma (HCC). HCC in NASH has a higher propensity to arise without pre-existing cirrhosis compared with other chronic liver diseases.METHODS:To identify the potential links between liver and gut in NASH-related hepatocarcinogenesis, we compared the gut microbiota and mediators of bile acid (BA) signaling in the absence or presence of cirrhosis through the analysis of stool and serum samples from patients with NASH non-HCC and NASH-HCC and healthy volunteers.RESULTS:Serum levels of total and individual BA were higher in NASH compared with healthy controls. Furthermore, serum levels of the primary conjugated BAs glycine-conjugated cholic acid, taurine-conjugated cholic acid, glycine-conjugated chenodeoxycholic acid, and taurine-conjugated chenodeoxycholic acid were significantly increased in cirrhotic vs noncirrhotic patients, independent of the occurrence of HCC. By contrast, serum FGF19 levels were higher in patients with NASH-HCC and associated with tumor markers as well as an attenuation of BA synthesis. Specific alterations in the gut microbiome were found for several bacteria involved in the BA metabolism including Bacteroides and Lactobacilli. Specifically, the abundance of Lactobacilli was associated with progressive disease, serum BA levels, and liver injury in NASH and NASH-HCC.DISCUSSION:Here, we demonstrate a clear association of the altered gut microbiota and primary conjugated BA composition in cirrhotic and noncirrhotic patients with NASH-HCC. Microbiota-associated alterations in BA homeostasis and farnesoid X receptor signaling, via FGF19, might thus contribute to fibrogenesis, liver injury, and tumorigenesis in NASH-HCC.

Association of serum FGF-23, klotho, fetuin-A, osteopontin, osteoprotegerin and hs-CRP levels with coronary artery disease

Environmental, genetic, oxidative and biochemical factors play an important role in the atherosclerotic process. We investigated the association of serum fibroblast growth factor (FGF-23), klotho, fetuin-A, osteoprotegerin (OPG), osteopontin (OPN) and high-sensitive-CRP (Hs-CRP) markers with coronary artery disease and whether one was superior to others or not. A study group of 52 patients with coronary artery disease (CAD) and a control group of 30 patients with angiographically normal epicardial coronary arteries were included in the study. Serum FGF-23, klotho, fetuin-A, OPN, OPG and Hs-CRP marker levels were studied. Patients with CAD were classified in two groups as low (SYNTAX ≤22, n = 29) and moderate-high (SYNTAX ≥ 23, n = 23) according to anatomic SYNTAX score. FGF-23 (p = .033), klotho (p < .001), fetuin-A (p = .005) and OPG (p = .001) serum marker levels were significantly lower in CAD patients than the control group. Serum levels of FGF-23 (p = .012), klotho (p = .001), fetuin-A (p = .015) and OPG (p = 0.002) were significantly different between SYNTAX tertiles and control group. Klotho (p = .025, odd ratio (OR) = 0.542, 95% confidence interval (CI): 0.317–0.926) and HT (p = .004, OR = 34.598, 95%CI:1.054–1135.657) were the independent predictors of CAD presence. Serum klotho levels of 91.48 pmol/L predicts the presence of CAD with 60% sensitivity and 96.55% specificity (p < .001, area under curve = 0.864, 95% CI = 0.768, 0.931). We found that serum klotho level is an independent predictor of presence, extent and severity of CAD.

Risk of Osteoporosis in Patients with Crohn’s Disease Not Respond to Infliximab Therapy Undergoing Surgical Intervention

Osteoporosis is one of the most common complications of Crohn’s disease (CD). Proper history with blood samples were collected from (30) healthy control group, (30) Crohn’s disease patients have been respond to biological therapy ( infliximabIFX) (response group) and (30) CD patients with (non-response group) to biological therapy undergoing surgical intervention for the estimation of some biochemical parameters. This study demonstrate a significant decrease in FGF-23 (fibroblast growth factor 23) and vitamin D Levels between (non- response group) and control group (p&lt; 0.01). Similary , parathyroid hormone (PTH) Levels were increased significantly ( p&lt; 0.01) in (non- response) group. Moreover the calcium (Ca) and phosphours (P) decreased significantly (p&lt; 0.01) in same group. While in CD patients that have been treated with infliximab only vitamin D and FGF 23 decreased significantly (p&lt; 0.01)compared with control group. Levels of Serum FGF23 are considerably lower in CD patients, It is independent pattern was not affected by type of treatment (medical or surgical) . Hypovitaminosis common finding in CD patient’s .Although CD is not disease of vit D deficiency but it clearly is a disease whose pathogenesis seems closely related to vit D Level.

Rostral ventrolateral medulla neuron activity is suppressed by Klotho and stimulated by FGF23 in newborn Wistar rats.

Hypertension often occurs in patients with chronic kidney disease (CKD). Considering the decrease in serum Klotho and increase in serum FGF23 levels in such patients, decreased Klotho and increased FGF23 levels were thought to be associated with hypertension. Presympathetic neurons at the rostral ventrolateral medulla (RVLM) contribute to sympathetic activity and regulation of blood pressure. Therefore, we hypothesized that Klotho would reduce the activities of RVLM neurons and FGF23 would stimulate them. Accordingly, this study examined the effects of Klotho and FGF23 on bulbospinal neurons in the RVLM. We used a brainstem-spinal cord preparation to record from RVLM presympathetic neurons and to evaluate the effects of Klotho and FGF23 on firing rate and membrane potentials of these neurons. Our results showed that Klotho-induced RVLM neuron hyperpolarization, while ouabain, a Na+/K+-ATPase inhibitor, suppressed the effects of Klotho on such neurons. Moreover, FGF23 induced RVLM neuron depolarization, while SU5402, an FGF23 receptor (FGFR1) antagonist, induced RVLM neuron hyperpolarization. Histological examinations revealed that Klotho, Na+/K+-ATPase, FGF23, and FGFR1 were present in RVLM neurons and that Klotho was localized in the same neurons as FGFR1. These results suggest that Klotho and FG23 regulate the activity of RVLM neurons. Klotho may reduce the activity of RVLM neurons via stimulating Na+/K+-ATPase on those neurons while FGF23 may activate those neurons via FGFR1.

The Level of FGF 21 as a New Risk Factor for the Occurrence of Cardiometabolic Disorders amongst the Psoriatic Patients.

Fibroblast growth factors 21 and 23 are used as markers of cardiometabolic disorders which are common comorbidities in psoriasis. The study aimed to evaluate the serum level of these factors in psoriatic patients and elucidate the possible interplay between disease activity, metabolic or inflammatory parameters, and systemic treatment. A total of 33 patients with active plaque-type psoriasis and 11 healthy controls were enrolled in the study. Patients were divided into subgroups based on their BMI, disease severity, and treatment. Blood samples were collected at the beginning of the study and after 3 months of systemic treatment with acitretin or methotrexate. Serum FGF21 levels in psoriatic patients were higher versus control group (p < 0.05). FGF21 levels regarding psoriasis activity were significantly increased in all three subgroups compared to the controls (p < 0.05). Regarding FGF23, no significant changes were found beside positive correlation with aspartate transferase (p < 0.05). No significant effect of systemic treatment on FGF21 and FGF23 levels was found. Interestingly, a nearly threefold decrease in FGF21 concentration after acitretin-based treatment was observed (p < 0.05). After methotrexate therapy, FGF21 levels remained unchanged. FGF21 levels might be helpful in prediction of the risk of cardiometabolic comorbidities development especially in patients with severe psoriasis and obesity.

KRĄŻĄCE MARKERY PRZEMIAN KOSTNYCH I ICH WZAJEMNE ZWIĄZKI U PACJENTÓW HEMODIALIZOWANYCH Z NIEDOBOREM WITAMINY D

Introduction: Mineral homeostasis is achieved through a complex interplay of several feedback processes involving primarily the bone, intestine and kidney, regulated by different proteins acting on endocrine, paracrine or autocrine levels. The dysregulation of these processes in chronic renal failure, called kidney disease (CKD) - mineral and bone disorder (CKD-MBD), although apparent, is still poorly understood. The aim: The aim of the study was an analysis of potential relationships between selected biomarkers of CKD-MBD in maintenance hemodialysis (HD) patients. Material and Methods: In the first part of this cross-sectional study, the 25(OH)D serum concentrations were measured in 115 HD vitamin D naïve patients from 5 dialysis units located in central Poland. Thereafter in 81 patients (49 men, 32 women, aged 67 ± 13 years) with vitamin deficiency (25(OH)D <20 ng/ml) serum concentrations of 25(OH)D, 1,25(OH)2D, intact parathyroid hormone (iPTH), intact FGF23, sclerostin (SCL), osteocalcin (OC), and C-terminal telopeptide of type I collagen (CTX1) were determined. Results: Serum levels of both 25(OH)D and 1,25(OH)2D were low (mean values 13.4±6.72 ng/ml and 12.9 ± 9.08 pmol/l, respectively). While serum 25(OH)D correlated only with a declared time spent outside (r= 0.411; p=0.000139), serum 1,25(OH)2D was related to diuresis (r= 0.289; p=0.009), and negatively to time on dialysis (r= -0.272; p=0.014) , serum phosphate (r= -0.393; p=0.000289), FGF23(r= -0.295; p=0.008), and SCL (r= -0.260; p=0.019). There was a marked dispersion of FGF-23 serum levels across the group (mean 823±5647, median 379 pg/ml) , and - as expected - they correlated highly with phosphate (r= 0.549, p=0.000), calcium (r= 0,328, p=0,003), OC (r=0.479; p=0.000), and negatively with z 1,25(OH)2D (r= -0.295, p=0.008). Mean serum SCL levels (89.2±46.7, median 81.9 pmol/l) were 3x higher than in general population, and correlated highly positively with dialysis vintage (r=0.402; p<0.001), age (r=0.356; p=0.001), as well as negatively with 1,25(OH)2D (r= -0.260; p=0.019) and CTX1 (r= -0.293; p=0.008). Conclusions: In our hemodialysis population, in addition to profoundly impaired 1,25(OH)2D synthesis, there is also a widespread prevalence of 25(OH)D deficiency. The patients have also markedly increased serum bone-secreted proteins, FGF23, and SCL, which regulate mineral and bone metabolism and are associated with the systemic side effects of uremia. All these hormones interact one with the other, creating a sophisticated cross-talk between the bone, intestine, and the kidney.

Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex.

Scope: Cytokines have pleiotropic functions within the organism and their levels may be influenced by obesity, visceral adiposity and sex hormones. Diet composition may also affect their systemic concentrations during fasting and in the postprandial period. Hence, we studied the influence of sex steroids and obesity on the circulating levels of a panel of metabolic cytokines in the fasting state and after single macronutrient challenges. Methods: On alternate days we submitted 17 women with polycystic ovary syndrome (PCOS) (9 non-obese, 8 obese), 17 non-hyperandrogenic control women (9 non-obese, 8 obese) and 19 control men (10 non-obese, 9 obese) to isocaloric oral glucose, lipid and protein loads. Serum levels of omentin-1, vaspin, lipocalin-2, adipsin, PAI-1, chemerin, FGF-21 and FGF-23 were determined by Luminex multiplex technology. Results: During fasting, obese patients presented higher levels of PAI-1, chemerin and adipsin but decreased FGF-23 and omentin-1 compared with non-obese subjects. Vaspin showed sexual dimorphism with lower levels in men than women with PCOS and female controls. Following macronutrient ingestion, most metabolic cytokines presented a similar physiological response consisting of a decrease in circulating concentrations, which was inversely associated with the fasting levels of these molecules. Protein intake caused the major postprandial decrease whereas glucose did not significantly reduce PAI-1, FGF-23 and vaspin, and even increased FGF-21. Regardless of the macronutrient administered, vaspin levels showed a larger reduction in non-obese individuals while the decrease in PAI-1 was particularly noticeable in the obese subgroup. The postprandial reductions of omentin-1 and FGF-23 after glucose and protein loads were influenced by obesity. No major differences were found between patients with PCOS and male and female controls. Conclusions: Obesity, but not PCOS or sex, markedly influences metabolic cytokine levels at fasting and after macronutrient ingestion. The observed postprandial decrease in their circulating concentrations might represent a physiological compensatory mechanism against food-induced inflammation and oxidative stress. This mechanism is altered by obesity and is differently modulated by macronutrients, suggesting a larger contribution of glucose to stressful postprandial responses.

Serum Levels of Fibroblast Growth Factor 23 in People Living with HIV.

Fibroblast growth factor (FGF) 23 is a well-known phosphaturic hormone produced mainly by bone cells to maintain phosphate and mineral homeostasis. Serum FGF23 levels are elevated in patients with chronic kidney disease (CKD), and elevated FGF23 might increase the risk of cardiovascular disease (CVD). Several reports have documented an increased incidence of risk factors for osteopenia, CKD, and CVD in people living with HIV (PLWH). However, few reports related to FGF23 in PLWH have been published. Male HIV patients who presented to the outpatient clinic of Teikyo University Hospital, Tokyo, Japan, in 2015 and were treated with antiretroviral therapy (ART) for > 6 months were enrolled in the study. In addition to serum FGF23 measurements, the clinical factors assessed included age, ART regimens, and laboratory data. Spearman correlation and multiple regression analysis were performed to determine factors significantly associated with FGF23. In total, 67 patients were enrolled in the present study. The median age was 43.7 years, the median CD4 count was 529 cells/μL, and the median serum FGF23 level was 36.0 pg/mL. Based on correlation and multiple regression analyses, serum FGF23 levels were significantly correlated with HIV RNA > 50 copies (correlation analysis: t = 3.4259, P = 0.0011 / multiple regression analysis: P = 0.00106) or abacavir (ABC)/lamivudine (3TC) use (t = 2.8618, P = 0.0057 / P = 0.02704). Factors significantly associated with elevated serum FGF23 levels included poor virologic control and ABC/3TC use.