Evaluation of maternal serum fibroblast growth factor-23 levels in fetal growth restriction and gestational hypertensive disease.

OBJECTIVE: The objective of this study was to determine serum fibroblast growth factor-23 levels in preeclampsia, eclampsia, gestational hypertension, and the presence of fetal growth restriction subgroups. METHODS: A total of 55 pregnant women with planned cesarean section were included in this cross-sectional study. They were divided into two groups, namely, control (25) and gestational hypertensive disease (30). The gestational hypertensive disease group was evaluated by dividing it into three subgroups (preeclampsia, eclampsia, and gestational hypertension) according to the clinical and laboratory findings of the disease and two subgroups (presence of fetal growth restriction and absence of fetal growth restriction) according to the birth weight percentile. Demographic parameters, obstetric history, physical examination findings, and laboratory values were evaluated. RESULTS: Demographic parameters and obstetric history were similar between the two groups, while gestational week of delivery was lower in the gestational hypertensive disease group (p=0.002). Laboratory parameters and serum fibroblast growth factor-23 (pg/mL) values were similar between the two groups. In the subgroup analysis for gestational hypertension, preeclampsia, and eclampsia, there was no statistically significant difference in serum fibroblast growth factor-23 levels between gestational hypertension, preeclampsia, eclampsia, and control groups. In the subgroup analysis based on the presence of fetal growth restriction, serum fibroblast growth factor-23 levels were similar to the control group in the gestational hypertensive disease absence of fetal growth restriction, while serum fibroblast growth factor-23 levels and serum calcium levels were statistically significantly lower in the gestational hypertensive disease with the presence of fetal growth restriction (p=0.044 and p<0.001, respectively). CONCLUSION: Serum fibroblast growth factor-23 levels are similar between pregnancies complicated with gestational hypertensive disease and normotensive pregnancies. However, serum fibroblast growth factor-23 levels were found to be lower in pregnancies complicated with gestational hypertensive disease with the presence of fetal growth restriction.

Interplay of clinical biomarkers in allergic asthma diagnosis and severity: A case-control study.

Given asthma's large phenotypic diversity, the study was aimed to use specific biomarkers to characterize Allergic asthma (AA) and its severity. Blood was collected from 42 healthy controls (HCs) and 96 patients with AA. Biomarkers related to blood cell number and function: total leukocyte count (TLCs), neutrophil, lymphocyte, monocyte, eosinophil, basophil, neutrophil-to-lymphocyte ratio (NLR), immunoglobulin E (IgE), tryptase and eosinophilic cationic protein (ECP) as well as remodelling biomarkers (Matrix metalloproteinase (MMP-9), (MMP-16), Fibroblast growth factor (FGF-18) and (FGF-23) and alpha-skeletal muscle actin-1 (ACTa-1) were measured. Significant differences were observed in hematological parameters with higher levels of total leukocytes, eosinophil, and basophil counts in the AA group compared to HCs. The disease group also had significantly higher levels of several serum biomarkers (IgE, TPs, ECP, MMP-9, MMP-16, FGF-18, FGF-23, and ACTa-1) compared to HC. Forced expiratory volume 1 (FEV1) and forced vital capacity (FVC) had a strong negative correlation with ECP, IgE, and ACTa-1. FEV1 was negatively correlated with MMP-16 and tryptase. Patients with AA have higher levels of several biomarkers, such as MMP-9, MMP-16, FGF-18, FGF-23, IgE, tryptase, and ACTa-1. In addition, IgE, tryptase, ACTa-1, and MMP-16 are related to lung function impairment in AA. This indicates that measuring multiple biomarkers may be of value in the future when diagnosing and monitoring AA.

Relationship between fibroblast growth factor in plasma and carotid plaque neovascularization: a pilot study.

Background: Unstable atherosclerotic carotid plaques with intraplaque neovascularization (IPN) carry a substantial risk for ischemic stroke. Conventional ultrasound methods fall short in detecting IPN, where superb microvascular imaging (SMI) has emerged as a promising tool for both visualizing and quantification. High levels of fibroblast growth factor 23 (FGF-23) have, in observational studies, been suggested as related to cardiovascular morbidity and mortality. The association of FGF-23 to atherosclerotic carotid plaque instability remains relatively unexplored. Methods: A cohort of twenty-nine patients with ≥50% atherosclerotic carotid stenosis underwent conventional carotid ultrasound, SMI, and blood tests, including measurement of FGF-23 in plasma. Nineteen patients were characterized as symptomatic and ten as asymptomatic. Results: Our major findings were: i) Higher FGF-23 levels were strongly correlated with increased SMI-assessed IPN. ii) Neo-vessel count recorded by quantitative SMI was positively correlated to increased FGF-23 levels, but not with basic FGF levels. (iii) In contrast, traditional risk factors for plaque instability exhibited no noteworthy associations with SMI-assessed IPN or with FGF-23 levels. Conclusion: This pilot study suggest the potential of FGF-23 as a valuable marker for neovascularization and atherosclerotic carotid plaque instability as a risk factor for ischemic stroke. Further research involving larger cohorts and prospective data is necessary to understand FGF-23's role in this context comprehensively.

Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

BACKGROUND: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.

Determinants of circulating calcitriol in cardiovascular disease.

Circulating calcitriol may contribute to the risk of cardiovascular disease (CVD), but its regulation in patients with CVD is poorly characterized. We therefore aimed to assess determinants of circulating calcitriol in these patients. We analyzed 2183 independent samples from a large cohort of patients scheduled for coronary angiography and 1727 independent samples from different other cohorts from patients with a wide range of CVDs, including heart transplant candidates, to quantify the association of different parameters with circulating calcitriol. We performed univariable and multivariable linear regression analyses using the mathematical function that fitted best with circulating calcitriol. In the multivariable analysis of the large single cohort, nine parameters remained significant, explaining 30.0 % (32.4 % after exclusion of 22 potential outliers) of the variation in circulating calcitriol (r=0.548). Log-transformed 25-hydroxyvitamin D [25(OH)D] and log-transformed glomerular filtration rate were the strongest predictors, explaining 17.6 % and 6.6 %, respectively, of the variation in calcitriol. In the analysis of the combined other cohorts, including heart transplant candidates, the multivariable model explained a total of 42.6 % (46.1 % after exclusion of 21 potential outliers) of the variation in calcitriol (r=0.653) with log-transformed fibroblast growth factor-23 and log-transformed 25(OH)D explaining 29.0 % and 6.2 %, respectively. Circulating 25(OH)D was positively and FGF-23 inversely associated with circulating calcitriol. Although significant, PTH was only a weak predictor of calcitriol in both analyses (<2.5 %). In patients with CVD, FGF-23 and 25(OH)D are important independent determinants of circulating calcitriol. The relative importance of these two parameters may vary according to CVD severity. Future studies should focus on the clinical importance of regulating circulating calcitriol by different parameters.

Fibroblast growth factor-23 and Alpha-Klotho concentrations in dogs with canine Leishmaniasis.

This study aimed to assess the concentrations of Fibroblast Growth Factor-23 (FGF-23) and α-Klotho in healthy dogs and dogs at different stages of Canine Leishmaniasis (CanL), and investigate the changes of these parameters in relation to renal function and calcium­phosphorus metabolism. A total of 74 dogs (22 healthy and 52 with CanL) of varying ages, sexes, and medium-sized breeds were included. Dogs with CanL were categorized into different stages (Stage I-IV) based on Leishvet recommendations. In addition to routine hematological parameters, plasma FGF-23, serum α-Klotho, urea, creatinine, phosphorus, calcium, parathormone, vitamin D concentrations, and urine protein/creatinine ratio were measured. Data from healthy dogs were compared to dogs with CanL overall and by stage. Dogs with CanL exhibited higher concentrations of FGF-23 (p < 0.05), α-Klotho, and parathormone (p < 0.001), as well as lower concentrations of vitamin D and calcium (p < 0.001). FGF-23 concentration was particularly elevated in Stage IV compared to other stages. However, no significant differences in α-Klotho levels were observed among the stages. FGF-23 levels showed a weak positive correlation with urea and creatinine concentrations and a moderate positive correlation with urine protein/creatinine ratio. This study demonstrated increased levels of FGF-23 and α-Klotho in dogs with CanL for the first time. The increase in FGF-23 levels was more prominent in advanced stages of the disease and correlated with higher urea and creatinine concentrations. These findings may serve as a basis for future diagnostic and therapeutic investigations, contributing to the understanding of the pathophysiology of kidney disease in CanL.

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus.

Diabetic retinopathy is a commonly observed cause of blindness and is a common problem in individuals with diabetes. Recent investigations have showed the capability of serum α-Klotho and FGF 23 in mitigating the effects of diabetic retinopathy. This study aimed to discover the correlation between FGF 23, α-Klotho, and diabetic retinopathy in type 1 diabetics. This case-control study included 63 diabetic patients and 66 healthy controls. Following an overnight duration of fasting, morning blood samples were taken from both the patient and the control groups. The serum concentrations of α-Klotho and FGF 23 were quantified. An experienced ophthalmologist inspected the retinopathy. All participants in this study have moderate non-proliferative retinopathy. A p value under 0.05 was considered statistically significant. The mean α-Klotho level for retinopathic diabetic patients was 501.7 ± 172.2 pg/mL and 579.6 ± 312.1 pg/mL for non-retinopathic diabetic patients. In comparison, α-Klotho level of the control group was 523.2 ± 265.4 pg/mL (p = 0.531). The mean of FGF 23 level did not demonstrate a significant difference (p = 0.259). The mean FGF 23 level were 75.7 ± 14.0 pg/mL, 74.0 ± 14.8 pg/mL and 79.3 ± 14.4 pg/mL in groups, respectively. In conclusion, there was no significant difference in FGF 23 and α-Klotho levels between type 1 diabetics with and without retinopathy when compared to the control group.

Fibroblast growth factor 23 levels in cord and peripheral blood during early neonatal period as possible predictors of affected offspring of X-linked hypophosphatemic rickets: report of three female cases from two pedigrees.

OBJECTIVES: The role of serum fibroblast growth factor 23 (FGF23) level in early neonatal period on the diagnosis of X-linked hypophosphatemic rickets (XLH) remains unclear. CASE PRESENTATION: Two female patients from the first pedigree had an affected mother, and the other female from the second pedigree had an affected father. In all three cases, FGF23 levels were high in cord blood and peripheral blood at day 4-5. Additionally, the FGF23 levels considerably increased from birth to day 4-5. We identified a PHEX pathogenic variant and initiated treatment during infancy in each case. CONCLUSIONS: In neonates with a parent diagnosed as PHEX-associated XLH, FGF23 in cord blood and peripheral blood at day 4-5 may be useful markers for predicting the presence of XLH.

A potential link between fibroblast growth factor-23 and the progression of AKI to CKD.

BACKGROUND: Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear. METHOD: Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFß/Smad and Wnt/ß-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis. RESULTS: The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of ß-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of ß-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells. CONCLUSION: The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-ß and Wnt/ß-catenin activation.

Prognostic Value of Combined Biomarkers in Patients With Heart Failure: The Heartmarker Score.

Background: Heart failure (HF) biomarkers have prognostic value. The aim of this study was to combine HF biomarkers into an objective classification system for risk stratification of patients with HF. Methods: HF biomarkers were analyzed in a population of HF outpatients and expressed relative to their cut-off values (N-terminal pro-B-type natriuretic peptide [NT-proBNP] >1,000 pg/mL, soluble suppression of tumorigenesis-2 [ST2] >35 ng/mL, growth differentiation factor-15 [GDF-15] >2,000 pg/mL, and fibroblast growth factor-23 [FGF-23] >95.4 pg/mL). Biomarkers that remained significant in multivariable analysis were combined to devise the Heartmarker score. The performance of the Heartmarker score was compared to the widely used New York Heart Association (NYHA) classification based on symptoms during ordinary activity. Results: HF biomarkers of 245 patients were analyzed, 45 (18%) of whom experienced the composite endpoint of HF hospitalization, appropriate implantable cardioverter-defibrillator shock, or death. HF biomarkers were elevated more often in patients that reached the composite endpoint than in patients that did not reach the endpoint. NT-proBNP, ST2, and GDF-15 were independent predictors of the composite endpoint and were thus combined as the Heartmarker score. The event-free survival and distance covered in 6 minutes of walking decreased with an increasing Heartmarker score. Compared with the NYHA classification, the Heartmarker score was better at discriminating between different risk classes and had a comparable relationship to functional capacity. Conclusions: The Heartmarker score is a reproducible and intuitive model for risk stratification of outpatients with HF, using routine biomarker measurements.

Comparative analysis of fibroblast growth Factor-23 as a correlate of cardiovascular disease among individuals with chronic kidney disease, hypertensives, and healthy controls.

Background: Chronic kidney disease (CKD) is a global growing public health epidemic with attending morbidity and huge financial cost. Cardiovascular disease (CVD), a major complication of CKD, contributes to its excessive mortality rate. The aetio-pathogenesis of the excess burden of CVD in CKD is a feature yet to be unravelled. Fibroblast growth factor-23 (FGF-23) has been implicated as a risk factor for CVD among patients with CKD. However, most of these studies were predominantly among the Caucasian population. Aim: This study aims to determine the correlation between FGF-23 and CVD among Nigerians with CKD. Patients and Methods: A cross-sectional comparative study composed of three groups: participants with CKD, hypertensives without CKD, and healthy individuals, represented as group 1, 2, and 3, respectively. Information obtained included demographic data and occurrence of risk factors for CVD. Cardiovascular risks were assessed by echocardiography and all the participants had kidney function tests done with plasma FGF-23. Results: The study sample size consisted of 135 participants. The mean (SD) age for participants with CKD and controls were 50.2 (12.7), 54.3 (15.5), and 40.2 (14.1) years, respectively. The median [interquartile range (IQR)] of plasma FGF-23 for participants with CKD 210 (139-304) RU/ml, and controls 124 (86-170) RU/ml, and 71 (38 - 89) RU/ml P < 0.001. Most participants with CKD had left ventricular hypertrophy (LVH) (80.0%), compared to the controls; 28.9% and 6.7% P < 0.001. Similarly, majority of participants with CKD had elevated plasma FGF-23 with LVH (85.7%) compared to controls 55.6% and 11.5%, whereas for aortic valve calcification with elevated plasma FGF-23 among CKD and controls were 53.6% (P = 0.29), 37.0% (P = 0.03), and 19.2% (P = 0.06), respectively. Conclusion: Individuals with CKD had frequencies of elevated plasma FGF-23, LVH, and cardiac valve calcification, which are surrogates of cardiovascular events.

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

BACKGROUND: 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. METHODS: 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 1 year in 62 pediatric patients with CKD (stages 2-5D, 1-16 years old). Factors related to changes in FGF23 levels were investigated. RESULTS: The median age of patients at the evaluation was 10.5 years (interquartile range 6.0-14.0), and the estimated glomerular filtration rate (eGFR) was 59.0 mL/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 66.5 pg/mL (48.3-96.4), and percent change in FGF23 levels after 1 year 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. CONCLUSIONS: An increase in TNF-α levels is associated with elevation of FGF23 levels in pediatric patients with CKD.

18-year change in serum intact fibroblast growth factor 23 from midlife to late life and risk of mortality: the ARIC Study.

Objective: Fibroblast growth factor 23 (FGF23) concentration increases in response to declining kidney function to preserve normal phosphate concentrations. However, the etiological association of change in FGF23 concentration with mortality has not been examined in the general population. Design and methods: We analyzed 5458 participants of the Atherosclerosis Risk in Communities Study who had intact FGF23 and estimated glomerular filtration rate (eGFR) assessed during midlife (visit 3, 1993-1995, mean age: 58 years) and late life (visit 5, 2011-2013, 76 years) to examine the association of FGF23 change over 18 years from mid-life to late life with the subsequent risk of mortality in late life using Cox regression models. Results: The median 18-year change in intact FGF23 was +17.3 pg/mL. During a median follow-up of 7.2 years following visit 5, 1176 participants died. In multivariable Cox models, elevated mortality was seen in the highest quartile of FGF23 change (ΔFGF23: ≥31.3 pg/mL) (adjusted hazard ratio (aHR): 1.61 (95%CI: 1.36-1.90), or 1.37 (1.15-1.64) after additionally adjusting for eGFR change, compared with the lowest quartile (≤6.4 pg/mL)). When both FGF23 change and FGF23 in late life were simultaneously entered into the Cox model, FGF23 in late life, but not FGF23 change, was an independent predictor of mortality; however, we observed a high correlation between FGF23 change from midlife to late life and FGF23 in late life (r = 0.77). Conclusions: Serum intact FGF23 change from midlife to late life was associated with subsequent risk of mortality independent of decline in kidney function. Our findings further support the implications of FGF23 beyond its association with kidney function.

Associations between endogenous sex hormones and FGF-23 among women and men in the Multi-Ethnic Study of Atherosclerosis.

Elevated levels of testosterone and fibroblast growth factor 23 (FGF-23) are both independently associated with a higher risk of cardiovascular disease (CVD). However, the relationship between sex hormones and FGF-23 is not well established. We explored the association between sex hormones and FGF-23 among middle-aged to older men and women in MESA. We studied 3,052 men and 2,868 postmenopausal women free of CVD at the time of enrollment with baseline serum sex hormones [total testosterone (T), free T, estradiol (E2) and sex hormone binding globulin (SHBG)] and intact FGF-23. In sex-stratified analyses, we examined the cross-sectional associations between log-transformed sex hormones (per 1 SD) and log-transformed FGF-23 using multiple linear regression adjusted for socio-demographics, CVD risk factors, estimated glomerular filtration rate and mineral metabolites (25-hydroxyvitamin D, calcium, phosphorus and parathyroid hormone). The mean (SD) age of study participants was 64 (10) years. The median (IQR) of FGF-23 was similar in women and men [38 (30-46) vs 38 (31-47) pg/mL]. In adjusted analyses, among women, 1 SD increment in free T was associated with 3% higher FGF-23 while SHBG was associated with 2% lower FGF-23. In men, 1 SD increment in E2 was associated with 6% higher FGF-23 whereas total T/E2 ratio was associated with 7% lower FGF-23. In conclusion, this exploratory analysis found that a more androgenic sex hormone profile was directly associated with FGF-23 in women and inversely associated with FGF-23 in men. Longitudinal studies are required to determine whether FGF-23 mediates the relationship between sex hormones and CVD risk.

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.

Correlation of fibroblast growth factor 23 and malnutrition in chronic kidney disease patients on maintenance hemodialysis.

Chronic Kidney Disease (CKD) is a major health problem that causes death and disability worldwide. Fibroblast growth factor - 23 (FGF 23), is a novel hormone, which is secreted primarily by the osteoblasts. CKD patients are at an increased risk of malnutrition, characterized by micronutrient deficiencies and protein-energy wasting. The mechanisms of malnutrition in CKD are complicated and involve multiple pathophysiologic alterations. Serum FGF 23 levels may be used as a marker of malnutrition in such patients. MATERIAL: 50 CKD patients on maintenance hemodialysis were selected after fulfilling inclusion and exclusion criteria and their anthropometric measurements and Subjective Global Assessment-Dialysis Malnutrition Score (SGA-DMS) score calculated, Serum FGF 23 levels and various other baseline characteristics and demographic information were collected from August 1, 2020 to March 31, 2021 in this cross-sectional observational study, which was done in the medicine wards of a tertiary care hospital in Delhi. OBSERVATION: The mean age of the study population was 42.44 ± 14.35 years. The mean Body Weight was 58.06 kg. The mean height was 1.72 m. The mean BMI was 19.73 kg/m2. The mean SGA-DMS Score was 30.12. The mean FGF 23 levels were 650.46 pg/mL. There was a strong negative correlation between SGA-DMS Score and FGF-23 (pg/ mL), and this correlation was statistically significant (rho = -0.72, p = <0.001). CONCLUSION: FGF 23 levels showed negative correlation with nutrition status of the patient and it can be used as a marker for malnutrition in CKD patients on maintenance hemodialysis.

Nephron index [urinary phosphate: serum fibroblast growth factor 23 ratio]- a marker for atherosclerosis in diabetic predialysis chronic kidney disease patients.

Chronic kidney disease (CKD) is a global health problem, a leading cause of death and disability worldwide, estimated to affect more than 10% of the population Fibroblast growth factor - 23 (FGF 23), is a novel hormone, which is secreted primarily by the osteoblasts. It has been proposed that the ratio of Urinary phosphate (U-P) excretion (mg/day) to FGF23 as an index that theoretically represents the number of nephrons (nephron index)1. In this study, an attempt was made to establish the relationship between the Nephron index and degree of atherosclerosis (CIMT-Carotid intimal medial thickness) in predialysis CKD patients. MATERIAL: 110 predialysis CKD patients were selected after fulfilling the inclusion and exclusion criteria and their CIMT, Serum FGF 23 levels and various other baseline characteristics and demographic information were collected from August 1, 2020 to March 31, 2021 in this cross-sectional observational study, which was done in the medicine wards of a tertiary care hospital in Delhi. OBSERVATION: The mean Age was 43.80 ± 15.08 years. The mean Body Weight (Kg) was 63.36 ± 8.37. The mean Nephron Index in the study population was 2.80 ± 3.55. The mean 24 hr urinary phosphate was 1026.03 ± 784.83 mg and the mean FGF-23 levels were 564.60 ± 194.16pg/ml. There was a moderate negative correlation between CIMT (mm) and Nephron Index (r = -0.39, p = <0.001). CONCLUSION: Nephron Index was found to have an association with age, S. Creatinine, S.Calcium, S.Phosphate, iPTH, 24-Hour Urinary PO4, FGF-23, CIMT, eGFR, CKD stage, and CIMT. Nephron index may be used as a marker for atherosclerosis in predialysis CKD patients.

Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients. METHODS: This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed. RESULTS: AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently. CONCLUSION: Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.

Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers.

The spectrum of diseases with overactive renin-angiotensin-aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography-mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m2. In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (ß: 0.0027; p = 4.2 × 10-7). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (ß: 0.0022; p = 2.1 × 10-5). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion.

Acute Effects of an Inorganic Phosphorus Additive on Mineral Metabolism and Cardiometabolic Risk Factors in Healthy Subjects.

CONTEXT: Hyperphosphatemia and high levels of fibroblast growth factor 23 (FGF23) are risk factors for cardiovascular events in patients with chronic kidney diseases. However, the impact of an inorganic phosphorus additive in healthy people is largely unknown. OBJECTIVE: We aimed to investigate the acute effect of excessive dietary phosphorus administered as sodium dihydrogen phosphate on the postprandial levels of Pi and FGF23 and the response to food. METHODS: This study was a double-blind placebo-controlled crossover study with 29 healthy male and female participants from the general community who were administered a single dose of either 700 mg phosphorus (NaH2PO4) or a sodium-adjusted placebo in combination with a test meal. Postprandial plasma levels of Pi and FGF23 were measured. RESULTS: Compared with placebo, oral phosphorus increased the plasma Pi level, which remained elevated during the ensuing 8 hours (at 480 minutes: 1.31 vs 1.16 mmol/l; P < 0.001), increased urinary Pi (iAUC0-480 789 vs 95 mmol/mmol; P < 0.001), reduced tubular Pi reabsorption (iAUC0-480 -31.5 vs -6.2; P < 0.001), decreased urinary calcium (iAUC0-240 30.6 vs 53.0 mmol/mmol; P = 0.009), and stimulated the release of parathyroid hormone (iAUC0-480 2212 vs 768 ng/l; P < 0.001). However, the FGF23 levels did not change. Postprandial levels of glucose, insulin, and lipids were not substantially affected by phosphorus vs placebo. CONCLUSION: An oral phosphorus load can induce elevated postprandial levels of circulating Pi for hours in healthy subjects, despite rapid homeostatic counterreactions. FGF23 levels and the postprandial response to food were not affected.