Search

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI. Methods: An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF1α, and ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting was used to measure the phosphorylation of extracellular signal-regulated kinase (ERK) level. Results: In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of ERK (p-ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham-operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, GPx, and p-ERK. In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and p-ERK, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells, but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, pro-inflammatory factor levels, oxidative stress response, and p-ERK levels. Conclusion: FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Both hypoxia and fibroblast growth factor-23 (FGF-23) are key factors in ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). This study aimed to explore the relationship between hypoxia and FGF-23 in AKI. Methods: An I/R-AKI animal model was established using male BALB/c mice. HK-2 cells, a part of the human proximal tubular epithelial cell line, were subjected to hypoxia/reoxygenation (H/R). qPCR was used to measure FGF-23 and HIF1α, and ELISA was used to measure inflammatory and oxidative stress cytokines. Western blotting was used to measure the phosphorylation of extracellular signal-regulated kinase (ERK) level. Results: In I/R mice, the levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), malondialdehyde (MDA), and the phosphorylation of ERK (p-ERK) were increased, whereas the levels of interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione peroxidase (GPx), and klotho were decreased, compared to the sham-operated mice. Silencing the FGF-23 expression in I/R mice normalized the levels of IL-6, IL-10, TNF-α, MDA, SOD, GPx, and p-ERK. In HK-2 cells, hypoxia-reperfusion (H/R) elevated the levels of IL-6, TNF-α, MDA, and p-ERK, but reduced IL-10, SOD, GPx, and klotho levels. Hypoxia induced apoptosis in HK-2 cells, but silencing of FGF-23 expression blocked the effects of hypoxia on cell apoptosis, pro-inflammatory factor levels, oxidative stress response, and p-ERK levels. Conclusion: FGF-23 is a key molecule in AKI, and hypoxia plays a crucial role in AKI by inducing cell apoptosis; however, its role is regulated by FGF-23. FGF-23 affects oxidative stress and the inflammatory response of kidney tissues by activating the ERK/mitogen-activated protein kinase (MAPK) signaling pathway.

Objectives X-linked hypophosphatemia (XLH) is characterized by increased concentrations of circulating fibroblast growth factor 23 (FGF-23) resulting in phosphate wasting, hypophosphatemia, atypical growth plate and bone matrix mineralization. Epidemiologic studies suggest a relationship between FGF-23, obesity, and metabolic dysfunction. The prevalence of overweight and obesity is high in children with XLH. We aimed to evaluate the prevalence of obesity and metabolic complications in adults with XLH. Methods We conducted a prospective cohort study in adult XLH patients from a single tertiary referral center. The proportion of patients with a BMI >25 kg/m2 was the main outcome measure. Body fat mass percentage (FM%) and adipose tissue surfaces were secondary outcome measures. Glucose homeostasis (plasma glucose and insulin concentrations after fasting and 2 hours after an oral glucose tolerance test) was explored in a subgroup of patients and compared with age-, sex-, and BMI-matched healthy controls. Results Among 113 evaluated patients, 85 (75%) were female and 110 (97%) carried a PHEX mutation. Sixty-three (56%) patients were overweight or obese, with a median BMI of 25.3 [IQR, 22.7; 29.2] kg/m2. BMI was correlated with FM%, abdominal and thigh subcutaneous and intra-abdominal adipose tissue surfaces. The prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetes was not different between XLH patients and matched controls. Conclusion The prevalence of overweight and obesity is high among XLH patients and is associated with excess fat mass. However, the prevalence of glucose homeostasis abnormalities is not increased in patients compared to healthy controls, suggesting that metabolically healthy overweight or obesity predominates. [ABSTRACT FROM AUTHOR]

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions. [ABSTRACT FROM AUTHOR]

Background Patients with autosomal dominant polycystic kidney disease (ADPKD) have disproportionately high levels of fibroblast growth factor 23 (FGF-23) for their chronic kidney disease stage, however only a subgroup develops kidney phosphate wasting. We assessed factors associated with phosphate wasting and hypothesize that it identifies patients with more severe disease and predicts disease progression. Methods We included 604 patients with ADPKD from a multicenter prospective observational cohort (DIPAK; Developing Intervention Strategies to Halt Progression of Autosomal Dominant Polycystic Kidney Disease) in four university medical centers in the Netherlands. We measured parathyroid hormone (PTH) and total plasma FGF-23 levels, and calculated the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) with <0.8 mmol/L defined as kidney phosphate wasting. We analysed the association of TmP/GFR with estimated GFR (eGFR) decline over time and the risk for a composite kidney outcome (≥30% eGFR decline, kidney failure or kidney replacement therapy). Results In our cohort (age 48 ± 12 years, 39% male, eGFR 63 ± 28 mL/min/1.73 m2), 59% of patients had phosphate wasting. Male sex [coefficient –0.2, 95% confidence interval (CI) –0.2; –0.1], eGFR (0.002, 95% CI 0.001; 0.004), FGF-23 (0.1, 95% CI 0.03; 0.2), PTH (–0.2, 95% CI –0.3; –0.06) and copeptin (–0.08, 95% CI –0.1; –0.08) were associated with TmP/GFR. Corrected for PTH, FGF-23 and eGFR, every 0.1 mmol/L decrease in TmP/GFR was associated with a greater eGFR decline of 0.2 mL/min/1.73 m2/year (95% CI 0.01; 0.3) and an increased hazard ratio of 1.09 (95% CI 1.01; 1.18) of the composite kidney outcome. Conclusion Our study shows that in patients with ADPKD, phosphate wasting is prevalent and associated with more rapid disease progression. Phosphate wasting may be a consequence of early proximal tubular dysfunction and insufficient suppression of PTH. [ABSTRACT FROM AUTHOR]

Background Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease–mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions. Methods We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study. FGF-23, calcium, phosphate, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH) in 1234 participants with pre-dialysis CKD (mean estimated glomerular filtration rate: 41.8 ± 14.3 mL/min) were analyzed. Mixed-effects general linear regression models adjusted for demographic and biological factors were used to compare repeated measurements across patient groups categorized by ethnicity (East Asian, White, South Asian, Black, Southeast Asian) and seasons. Results Compared with other groups, White participants exhibited 8.0%–18.5% higher FGF-23 levels, Black participants had 0.17–0.32 mg/dL higher calcium levels, White participants had 10.0%–20.1% higher 25-OHD levels, South Asian participants had 7.3%–20.1% lower 25-OHD levels and Black participants had 22.1–73.8% higher iPTH levels, while East Asian participants had 10.7%–73.8% lower iPTH levels. Seasonal variations were also observed. FGF-23 levels were 11.9%–15.5% higher in summer compared with other seasons, while calcium levels were 0.03–0.06 mg/dL lower in summer. 25-OHD levels were 5.6%–10.6% higher in summer and autumn compared with other seasons. Conclusions This study shows that FGF-23 and CKD-MBD markers in a Canadian pre-dialysis CKD cohort vary independently by ethnicity and season. Further research is needed to understand the reasons and clinical significance of these findings. [ABSTRACT FROM AUTHOR]

Background: Omentin-1 is mainly expressed in stromal vascular cells of adipose tissue and can also be expressed in airway goblet cells, mesothelial cells, and vascular cells. Fibroblast growth factor 23 (FGF-23), generated by bone cells, regulates phosphate and vitamin D metabolism by regulating phosphate reabsorption in the kidneys and inhibiting vitamin D activation. Vitamin D is a fat-soluble vitamin that regulates calcium absorption, bone health, and immunological function. Prostate cancer is a significant health concern for men worldwide. Several studies demonstrated a link between these variables and cancer as they exert important anti-inflammatory, antioxidative, and anti-cancer functions. Objectives: To assess the impact of Omentin and FGF-23 biochemical functions, as well as the anti-cancer properties of vitamin D. Subjects and methods: This is a case-control study on serum samples collected from Iraqi prostate cancer patients after receiving chemotherapy at Al Amal Center in Imam Hussein Medical City in Karbala between November 2022 to May 2023. The serum samples were collected from two groups: control group consisted of 30 healthy males. Patient group consisted of 30 prostate cancer patients after receiving chemotherapy, both groups aged 45 – 80 years. The two groups were matched for body mass index. ELISA technology was used to estimate serum levels of the aforementioned biochemical parameters with vitamin D. Results: patient group had a significantly higher FGF-23 level than control group (309.5±41.65) versus (163.1±22.4) (p

Introduction: Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost. Methods: Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2). Results: SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2. Conclusions: SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL. [ABSTRACT FROM AUTHOR]

Copyright of Paediatrics & Family Medicine / Pediatria i Medycyna Rodzinna is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation are the preferred treatment. Information on bone microarchitecture parameters assessed by high-resolution peripheral quantitative computed tomography is limited. We report a woman with hypophosphatemic osteomalacia with generalized pain, weakness and recurrent fractures, and a large thoracic vertebral mass extending to the posterior mediastinum. Detailed radiologic and histopathologic evaluation revealed a phosphaturic mesenchymal tumor. Two surgeries were necessary for complete removal of the mass. Clinical symptoms improved after attaining normophosphatemia. Four-year post-surgical HR-pQCT parameters, compared to baseline, showed in the left distal radius, stable trabecular and cortical volumetric bone mineral density although below reference range. There was stability of trabecular number and thickness. Both stiffness and failure load decreased. A shift in cortical parameters was noted in year 2. In the left distal tibia, trabecular volumetric bone mineral density decreased whereas cortical volumetric bone mineral density markedly increased, as did cortical area. There was stability in the trabecular number and thickness. Both stiffness and failure load improved. Findings from HR-pQCT measurements in this patient disclosed that the healing of osteomalacia is not similar across the peripheral skeletal sites in the first years following tumor removal. Results contrasted low but stable volumetric bone mineral density in the distal radius with increase in the distal tibia at the expense of cortical bone. Our report helps further delineate the pattern of bone healing after treatment of this rare bone disorder.

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

Phosphaturic mesenchymal tumors (PMT) are rare neoplasms, which can give rise to a multifaceted syndrome, otherwise called tumor-induced osteomalacia (TIO). Localizing these tumors is crucial to obtain a cure for the phosphate metabolism derangement, which is often the main cause leading the patient to seek medical help, because of invalidating physical and neuromuscular symptoms. A proportion of these tumors is completely silent and may grow unnoticed, unless they become large enough to produce pain or discomfort. FGF-23 can be produced by several benign or malignant PMTs. The phosphate metabolism, radiology and histology of these rare tumors must be collectively assessed by a multidisciplinary team aimed at curing the disease locally and improving patients’ quality of life. This narrative review, authored by multiple specialists of a tertiary care hospital center, will describe endocrine, radiological and histological features of these tumors, as well as present surgical and interventional strategies to manage PMTs.

Tumor-induced osteomalacia (TIO) is an ultra-rare disease caused mostly by benign tumors that secrete fibroblast growth factor-23. Because of nonspecific symptoms, the diagnostic delay is long, and therapy can be challenging. Moreover, epidemiological data on TIO are scarce owing to its rarity. Therefore, this study aimed to quantify TIO's incidence rates and prevalence in Germany. Retrospective longitudinal and cross-sectional analyses were conducted using anonymized German claims data from the statutory health insurance (SHI) database. This database, which comprises the data of approximately 5 million insurants, is a representative sample of the German population and supports national projections. As there is no unique International Statistical Classification of Diseases and Related Health Problems (ICD) code for TIO, operational categories based on different surrogates were defined to determine the prevalence and incidence rates of TIO among probable patients. This study showed that TIO has a prevalence of (documented code, advanced imaging, medication, or tumor removal) 0.187 per 100,000 persons and an incidence rate of ≤ 0.094 per 100,000 person years. This analysis provides the first epidemiological insight into German patients with TIO. Despite the general limitations associated with the analysis of SHI claims data of ultra-rare diseases, we believe that this analysis provides a sound basis for further analysis, particularly with regard to the care situation of patients with TIO. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ankara University Faculty of Medicine / Ankara Üniversitesi Tip Fakültesi Mecmuasi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: ferric carboxymaltose (CF) is an intravenous preparation that helps the rapid correction of anemia with a lower risk of adverse reactions. However, an association has been found between the administration of CF and the development of hypophosphatemia. Case report: we present the clinical case of a 57-year-old patient with a history of iron de-ficiency anemia who, after receiving treatment with CF (Ferinjet®) chronically, develops a clinical of severe muscle weakness. Laboratory tests showed hypophosphatemia, normocalcemia, normal vitamin D level (after correction) and increased renal excretion of phosphorus. After study, the diagnosis of chronic hypophosphatemia secondary to the use of CF is reached. Discussion: CF can cause an increase in FGF-23 which acts at the renal level inducing phosphaturia, which can generate severe hypophosphatemia. This case demonstrates the importance of recognizing and treating this clinical entity in time. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Fibroblast growth factor-23 (FGF-23) is a biomarker for the monitoring of chronic kidney disease in humans. The clinical relevance of FGF-23 in dogs is largely unknown. The aim of this study was (1) to show the intra- and interassay precision of the Kainos ELISA FGF-23 kit, (2) to determine a reference interval for FGF-23 in dogs, and (3) to investigate the possible correlations of the FGF-23 concentrations with other hematological and biochemical parameters. The coefficient of variation was <15% for both the intra- and interassay precision. The reference interval ranged between 95.8 (90% confidence interval: 44.6; 139.2) and 695.1 pg/mL (598.7; 799.1) in 136 clinically healthy dogs. For the correlation analysis, four groups were retrospectively formed based on the creatinine concentration classification according to the IRIS guidelines, including 10 dogs each. Strong positive correlations were detected between the FGF-23 concentration and the renal parameters. Statistically significant differences in the FGF-23 concentrations were demonstrated between study groups I and III (p < 0.001), I and IV (p < 0.001), and II and IV (p = 0.005). Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aims of this study were (1) to determine the intra- and interassay precision of the FGF-23 concentrations in dogs as measured via the Kainos ELISA FGF-23 kit, (2) to calculate a reference interval, and (3) to assess the correlation of the FGF-23 concentration with the hematological and biochemical parameters. The coefficient of variation was below 15% for both the intra- and interassay precision, indicating good reproducibility. The reference interval ranged between 95.8 (90% confidence interval: 44.6; 139.2) and 695.1 pg/mL (598.7; 799.1) based on 136 clinically healthy dogs, classified as such according to the information of treating veterinarians as well as the unremarkable results of hematology and biochemistry. The FGF-23 concentration differed significantly between dogs aged <9 and ≥9 years (p = 0.045). Four groups of 10 dogs each were retrospectively formed based on the creatinine concentration classification according to the IRIS staging. Correlation was the strongest for the renal parameters. Statistically significant differences in the FGF-23 concentration were demonstrated between the study groups I and III (p < 0.001), I and IV (p < 0.001), and II and IV (p = 0.005). There was a trend for a rising FGF-23 concentration in older dogs. Due to the wide reference interval, diagnostic cut-offs and/or subject-based FGF-23 reference values in each dog are needed for monitoring and clinical interpretation. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 23 (FGF-23) has been associated with increased cardiovascular risk and poor survival in dialysis patients. It is well established that FGF-23 synthesis is directly induced by positive phosphate (P) balance. On the other hand, P-lowering treatments such as nutritional P restriction, P binders and dialysis are capable of reducing FGF-23 levels. However, there are many uncertainties regarding the possibility of adopting FGF-23 to guide the clinical decision-making process in the context of chronic kidney disease–mineral bone disorder (CKD-MBD). Furthermore, the best assay to adopt for measurement of FGF-23 levels (namely the intact vs the C-terminal one) remains to be determined, especially in conditions capable of altering the synthesis as well as the cleavage of the intact and biologically active molecule, as occurs in the presence of CKD and its complications. This Editorial discusses the main insights provided by the post hoc analysis of the NOPHOS trial, with particular attention given to evidence-based peculiarities of the intact and the C-terminal assays available for measuring FGF-23 levels, especially in patients receiving additive P-lowering therapy in the presence of inflammation, anemia and iron deficiency. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bipolar disorder (manic episode) is an essential psychiatric dis-order with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are known to be associated with inflammation. Therefore, this study aimed to determine the link between Klotho and FGF-23 levels and bipolar disorder. PATIENTS AND METHODS: In this study, 42 men with BD and 41 healthy controls were enrolled, followed up, and/or treated at the High-Security Forensic Psychiatry Clinic. Sociodemographic data form, Young Mania Rating Scale, and Hamilton Depression Rating Scale were applied to all participants. RESULTS: Klotho and FGF-23 levels were significantly increased in patients with BD manic episodes. There was no correlation between Klotho and FGF-23 levels and clinical parameters. For Klotho and FGF-23, cutoff values of 69 and 1,646 yielded 67.4% sensitivity and 72.1% specificity and 81.4% sensitivity and 51.2% specificity, respectively. CONCLUSIONS: Klotho and FGF-23 may play critical roles in the etiopathology of manic episodes and are potential candidate biomarkers for bipolar disorder. This relationship might con-tribute to the etiopathogenesis of the disease and determine its treatment. Anti-Klotho and anti-FGF-23 administration may be a future treatment for controlling the course of the disease. [ABSTRACT FROM AUTHOR]

Abstract 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 TGFβ/Smad and Wnt/β-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

The consumption of ultra-processed food (UPF) keeps rising, and at the same time, an increasing number of epidemiological studies are linking high rates of consumption of UPF with serious health outcomes, such as cardiovascular disease, in the general population. Many potential mechanisms, either in isolation or in combination, can explain the negative effects of UPF. In this review, we have addressed the potential role of inorganic phosphate additives, commonly added to a wide variety of foods, as factors contributing to the negative effects of UPF on cardiorenal disease. Inorganic phosphates are rapidly and efficiently absorbed, and elevated serum phosphate can lead to negative cardiorenal effects, either directly through tissue/vessel calcification or indirectly through the release of mineral-regulating hormones, parathyroid hormone, and fibroblast growth factor-23. An association between serum phosphate and cardiovascular and bone disease among patients with chronic kidney disease is well-accepted by nephrologists. Epidemiological studies have demonstrated an association between serum phosphate and dietary phosphate intake and mortality, even in the general American population. The magnitude of the role of inorganic phosphate additives in these associations remains to be determined, and the initial step should be to determine precise estimates of population exposure to inorganic phosphate additives in the food supply. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to systematically review research on cinacalcet and secondary hyperparathyroidism (SHPT) using machine learning-based statistical analyses. Methods: Publications indexed in the Web of Science Core Collection database on Cinacalcet and SHPT published between 2000 and 2022 were retrieved. The R package “Bibliometrix,” VOSviewer, CiteSpace, meta, and latent Dirichlet allocation (LDA) in Python were used to generate bibliometric and metaanalytical results. Results: A total of 959 articles were included in our bibliometric analysis. In total, 3753 scholars from 54 countries contributed to this field of research. The United States, Japan, and China were found to be among the three most productive countries worldwide. Three Japanese institutions (Showa University, Tokai University, and Kobe University) published the most articles on Cinacalcet and SHPT. Fukagawa, M.; Chertow, G.M.; Goodman W.G. were the three authors who published the most articles in this field. Most articles were published in Nephrology Dialysis Transplantation, Kidney International, and Therapeutic Apheresis and Dialysis. Research on Cinacalcet and SHPT has mainly included three topics: 1) comparative effects of various treatments, 2) the safety and efficacy of cinacalcet, and 3) fibroblast growth factor-23 (FGF-23). Integrated treatments, cinacalcet use in pediatric chronic kidney disease, and new therapeutic targets are emerging research hotspots. Through a meta-analysis, we confirmed the effects of Cinacalcet on reducing serum PTH (SMD = -0.56, 95% CI = -0.76 to -0.37, p = 0.001) and calcium (SMD = -0.93, 95% CI = -1.21to -0.64, p = 0.001) and improving phosphate (SMD = 0.17, 95% CI = -0.33 to -0.01, p = 0.033) and calcium-phosphate product levels (SMD = -0.49, 95% CI = -0.71 to -0.28, p = 0.001); we found no difference in all-cause mortality (RR = 0.97, 95% CI = 0.90 to 1.05, p = 0.47), cardiovascular mortality (RR = 0.69, 95% CI = 0.36 to 1.31, p = 0.25), and parathyroidectomy (RR = 0.36, 95% CI = 0.09 to 1.35, p = 0.13) between the Cinacalcet and non-Cinacalcet users. Moreover, Cinacalcet was associated with an increased risk of nausea (RR = 2.29, 95% CI = 1.73 to 3.05, p = 0.001), hypocalcemia (RR = 4.05, 95% CI = 2.33 to 7.04, p = 0.001), and vomiting (RR = 1.90, 95% CI = 1.70 to 2.11, p = 0.001). Discussion: The number of publications indexed to Cinacalcet and SHPT has increased rapidly over the past 22 years. Literature distribution, research topics, and emerging trends in publications on Cinacalcet and SHPT were analyzed using a machine learning-based bibliometric review. The findings of this meta analysis provide valuable insights into the efficacy and safety of cinacalcet for the treatment of SHPT, which will be of interest to both clinical and researchers. [ABSTRACT FROM AUTHOR]

Phosphaturic mesenchymal tumors (PMT) are rare neoplasms, which can give rise to a multifaceted syndrome, otherwise called tumor-induced osteomalacia (TIO). Localizing these tumors is crucial to obtain a cure for the phosphate metabolism derangement, which is often the main cause leading the patient to seek medical help, because of invalidating physical and neuromuscular symptoms. A proportion of these tumors is completely silent and may grow unnoticed, unless they become large enough to produce pain or discomfort. FGF-23 can be produced by several benign or malignant PMTs. The phosphate metabolism, radiology and histology of these rare tumors must be collectively assessed by a multidisciplinary team aimed at curing the disease locally and improving patients' quality of life. This narrative review, authored by multiple specialists of a tertiary care hospital center, will describe endocrine, radiological and histological features of these tumors, as well as present surgical and interventional strategies to manage PMTs. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) confront with cardiovascular disease (CVD) complications which can be ameliorated with exercise. The purpose of the current study was to determine the effect of resistance training on pathological cardiac hypertrophy and FGF23-Klotho axis-induced adverse cardiovascular outcomes in rat model of CKD. Thirty male Wistar rats (7–8 weeks old) were randomly divided into three groups of the 5/6 nephrectomy (5/6NX) with and without resistance training and control group. The resistance training protocol consisted of 3 sessions per week. The proposed blood factors (Klotho, FGF23, serum phosphorus, parathyroid hormone, serum calcium, and vitamin D) evaluated for three groups at the end of 8th week. After confirming the normal distribution of data through Kolmogorov–Smirnov test, data analysis was performed by one-way ANOVA and Bonferroni post hoc test (P > 0.05). The effect of resistance training was significantly different between 3 groups of study for hypertrophy (P = 0.036) and cardiac function (P = 0.004). There was also a significant difference for blood factors of Klotho (P = 0.000), FGF23 (P = 0.043), serum phosphorus (P = 0.00), and parathyroid (P = 0.00). Serum calcium (P = 0.06) and vitamin D status (P = 0.06) improved but the differences were not significant. Resistance training can prevent progression of pathological cardiac hypertrophy in patients with renal disease. In the process of this improvement, changes in FGF23 and Klotho were significant; however, the vitamin D and calcium have played a less important role. [ABSTRACT FROM AUTHOR]

Rationale & objectiveChronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.Study designObservational study.Participants702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.PredictorsPlasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).OutcomesNeurocognitive tests of intelligence, academic achievement, and executive functions.Analytical approachLinear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.ResultsAt baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73 m2. In fully adjusted analyses, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log2FGF-23 was associated with abnormal test scores for attention regulation (P

The purpose of the study is to investigate the clinical significance of determination of serum FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD). Materials and Methods: The study included 70 patients with CKD stages 1–5D (30 men and 40 women, mean age 41,0–6,7 years), in whom the serum levels of FGF-23 and Klotho, as well as work Ca х P and the content of intact parathyroid hormone (iPTH). Results: the progression of CKD from stage 1 to 5D serum concentration of FGF-23 was increased, and the concentration of Klotho decreased. Glomerular filtration rate (GFR) was directly correlated with the serum concentration of FGF-23 (r=0,693, p

Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms – overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene – can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65

The role of vitamin D in primary osteoarthritis (OA) has not been clarified yet. vitamin D receptor (VDR) and fibroblast growth factor-23 (FGF-23) are proteins that play an important role in the metabolism of vitamin D. In this preliminary study, we aimed to examine serum 25-(OH) vitamin D3, VDR, and FGF-23 levels in primary knee OA patients.

BackgroundThe aim of this study was to investigate the association between inflammatory plasma protein concentrations and long-term mortality in patients with ST-elevation myocardial infarction (STEMI).MethodsFor 343 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 inflammatory plasma proteins were measured at the index event using the OLINK inflammation panel. In multivariable-adjusted Cox regression models, the association between each plasma protein and all-cause long-term mortality was investigated. Median follow-up time was 7.6 (IQR: 2.4) years. For plasma protein that showed a strong association with long-term mortality, a 5-year survival ROC analysis was performed.ResultsOne plasma protein, namely Fibroblast Growth Factor 23 (FGF-23), was particularly well associated with long-term mortality in the multivariable-adjusted Cox model with an FDR-adjusted p-value of 0.05 in the multivariable-adjusted Cox models.ConclusionsFGF-23 is independently associated with long-term mortality after STEMI and might play an important role in the response to myocardial injury. The results suggest FGF-23 to be a useful marker in the long-term treatment of STEMI patients and a potential target for drug development.

BackgroundIn the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race.MethodsOf 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function.ResultsSixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024).ConclusionsAmong men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.

The fibroblast growth factor FGF-23 is a member of the FGF-15/19 subfamily with hormonal functions. Besides its well-known role for bone mineralization, FGF-23 is discussed as a marker for cardiovascular disease. We investigated whether FGF-23 has any effects on the endocrine pancreas of mice by determining insulin secretion, electrical activity, intracellular Ca2+, and apoptosis. Acute application of FGF-23 (10 to 500 ng/ml, i.e., 0.4 to 20 nM) does not affect insulin release of murine islets, while prolonged exposure leads to a 21% decrease in glucose-stimulated secretion. The present study shows for the first time that FGF-23 (100 or 500 ng/ml) partially protects against impairment of insulin secretion and apoptotic cell death induced by glucolipotoxicity. The reduction of apoptosis by FGF-23 is approximately twofold higher compared to FGF-21 or FGF-15/19. In contrast to FGF-23 and FGF-21, FGF-15/19 is clearly pro-apoptotic under control conditions. The beneficial effect of FGF-23 against glucolipotoxicity involves interactions with the stimulus-secretion cascade of beta-cells. Electrical activity and the rise in the cytosolic Ca2+ concentration of islets in response to acute glucose stimulation increase after glucolipotoxic culture (48 h). Co-culture with FGF-23 further elevates the glucose-mediated effects on both parameters. Protection against apoptosis and glucolipotoxic impairment of insulin release by FGF-23 is prevented, when calcineurin is inhibited by tacrolimus or when c-Jun N-terminal kinase (JNK) is blocked by SP600125. In conclusion, our data suggest that FGF-23 can activate compensatory mechanisms to maintain beta-cell function and integrity of islets of Langerhans during excessive glucose and lipid supply. [ABSTRACT FROM AUTHOR]

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

Background: The diagnosis of phosphaturic mesenchymal tumors (PMT) is easily delayed clinically, and their surgical treatment is unstandardized. This study aimed to evaluate our experience in the diagnosis and treatment of PMT and provide a research basis for the accurate and standardized treatment of PMT. Materials and Methods: Twelve patients diagnosed with PMT in our department and who underwent surgical treatment were included in this study. Preoperative demographic and clinical information were recorded. CT, MRI, and technetium-99m (Tc99m)-octreotide PET/CT imaging techniques were used to evaluate the general conditions and lesion boundaries of the tumors. Surgical treatment was performed using radical resection and microwave ablation-assisted extended curettage according to the lesion location and size. Patients were strictly followed up with and evaluated for oncological prognosis, radiological results, bone healing, serum ion levels, limb function, and pain level; the occurrence of complications was also recorded. Results: Three patients underwent radical resection, and nine underwent microwave ablation-assisted extended curettage. The average duration of symptoms in this group was 1.5 years (9–35 months) before diagnosis. Serum phosphate and AKP levels returned to normal one and two weeks postoperatively, respectively. There was no apparent specificity in the pathological findings; however, the immunohistochemistry of FGF-23 was positive, and the original fracture sites were effectively healed during the follow-up. The limb function and pain scores were significantly improved. The MSTS score increased from 15.3 to 29.0, and the VAS score decreased from 5.3 to 0.4. All patients recovered, and 90% resumed their original jobs. Conclusions: Accurate diagnosis and standardized surgical treatment are crucial to achieving a clinical cure for PMT. Combining clinical manifestations, biochemical examinations, imaging characteristics, and pathological findings is an effective way to diagnose PMT accurately. Radical resection and microwave ablation-assisted extended curettage are reliable surgical treatment methods for PMT. [ABSTRACT FROM AUTHOR]

Loss of function mutations in the PHEX gene could determine X-linked dominant hypophosphatemia. This is the most common form of genetic rickets. It is characterized by renal phosphate wasting determining an increase in fibroblast growth factor 23 (FGF-23), growth retard, bone deformities and musculoskeletal manifestations. In recent decades, analysis of the PHEX gene has revealed numerous different mutations. However, no clear genotype-phenotype correlations have been reported in patients with hypophosphatemic rickets (XLH). We report two cases of a 28-year-old-male (patient 1) and a 19-year-old male (patient 2) affected by XLH initially treated with phosphate and 1,25-dihydroxyvitamin–D admitted to the Endocrinology unit because of the persistence of muscle weakness, bone pain and fatigue. After phosphate withdrawal, both patients started therapy with burosumab and symptoms ameliorated in three months. However, patient 1's biochemical parameters did not improve as expected so we decided to investigate his genetic asset. We herein describe a possible clinical implication for the missense "de novo" mutation, c.250G>C (p.Ala84Pro) in the PHEX gene, reported in the PHEX database and classified as a variant of uncertain significance (VUS). The clinical implication of this mutation on disease burden and quality of life in adults is still under investigation. [ABSTRACT FROM AUTHOR]

Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) comprises alterations in calcium, phosphorus, parathyroid hormone (PTH), Vitamin D, and fibroblast growth factor-23 (FGF-23) metabolism, abnormalities in bone turnover, mineralization, volume, linear growth or strength, and vascular calcification leading to an increase in bone fractures and vascular disease, which ultimately result in high morbidity and mortality. The bone component of CKD-MBD, referred to as renal osteodystrophy, starts early during the course of CKD as a result of the effects of progressive reduction in kidney function which modify the tight interaction between mineral, hormonal, and other biochemical mediators of cell function that ultimately lead to bone disease. In addition, other factors, such as osteoporosis not apparently dependent on the typical pathophysiologic abnormalities resulting from altered kidney function, may accompany the different varieties of renal osteodystrophy leading to an increment in the risk of bone fracture. After kidney transplantation, these bone alterations and others directly associated or not with changes in kidney function may persist, progress or transform into a different entity due to new pathogenetic mechanisms. With time, these alterations may improve or worsen depending to a large extent on the restoration of kidney function and correction of the metabolic abnormalities developed during the course of CKD. In this paper, we review the bone lesions that occur during both CKD progression and after kidney transplant and analyze the factors involved in their pathogenesis as a means to raise awareness of their complexity and interrelationship. [ABSTRACT FROM AUTHOR]

Asymmetric dimethylarginine (ADMA) is a marker of endothelial damage. Research confirms the association of ADMA with an increased cardiovascular risk (CVR) among kidney transplant recipients (KTRs). Additionally, increased circulating levels of fibroblast growth factor 23 (FGF-23) are associated with pathological cardiac remodeling and vascular alterations. The aim of the study is the analysis of the relationship between ADMA, FGF-23, nutritional, biochemical parameters in healthy subjects and KTRs. 46 KTRs and 23 healthy volunteers at mean age of 50.8 ± 15.4 and 62.5 ± 10.7 years were enrolled. The anthropometric and biochemical parameters such as ADMA, FGF-23, albumin, prealbumin were assessed. Fat tissue mass among KTRs was 30.28 ± 9.73%, lean body mass 64.5 ± 14.8%. Overweight and obesity was presented by 65.2% of recipients. Albumin level was 38.54 ± 3.80 g/L, prealbumin 27.83 ± 7.30 mg/dL and were significantly lower than in the control (p < 0.05). Patients with ADMA > 0.66 µmol/L had a lower concentration of prealbumin, albumin and increased concentration of oxidized low density lipoprotein (oxLDL), high sensitive C-reactive protein (hsCRP) and FGF-23. FGF-23 was significantly higher in patients with higher hsCRP (p < 0.05). KTRs with elevated ADMA had a longer transplantation vintage, lower eGFR and higher albuminuria. Diabetes mellitus (DM) was associated with higher levels of ADMA and FGF-23. Even in stable KTRs a relationship between inflammatory state, nutritional status, graft function and endothelial dysfunction biomarkers was observed.

Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aims of this study were (1) to determine the intra- and interassay precision of the FGF-23 concentrations in dogs as measured via the Kainos ELISA FGF-23 kit, (2) to calculate a reference interval, and (3) to assess the correlation of the FGF-23 concentration with the hematological and biochemical parameters. The coefficient of variation was below 15% for both the intra- and interassay precision, indicating good reproducibility. The reference interval ranged between 95.8 (90% confidence interval: 44.6; 139.2) and 695.1 pg/mL (598.7; 799.1) based on 136 clinically healthy dogs, classified as such according to the information of treating veterinarians as well as the unremarkable results of hematology and biochemistry. The FGF-23 concentration differed significantly between dogs aged p = 0.045). Four groups of 10 dogs each were retrospectively formed based on the creatinine concentration classification according to the IRIS staging. Correlation was the strongest for the renal parameters. Statistically significant differences in the FGF-23 concentration were demonstrated between the study groups I and III (p < 0.001), I and IV (p < 0.001), and II and IV (p = 0.005). There was a trend for a rising FGF-23 concentration in older dogs. Due to the wide reference interval, diagnostic cut-offs and/or subject-based FGF-23 reference values in each dog are needed for monitoring and clinical interpretation.

Introduction Obesity and metabolic syndrome are increasingly common in the adult population. There is a well- -known relationship between those two conditions and cardiovascular diseases; nonetheless, not much is known about how obesity and metabolic syndrome affect bone metabolism and fracture risk. The study aimed to assess the parameters of bone metabolism, as well as assess their relationship with the risk of fractures in obese men with central obesity and metabolic syndrome, and to compare the obtained results with those of healthy controls. Material and methods The study involved 36 obese men (body mass index – BMI ≥ 30) with central obesity (waist circumference – WC ≥ 94) and 10 healthy men as controls, aged 54–77. The FRAX (Fracture Risk Assessment Tool) calculator was used to measure the 10-year fracture risk. The levels of bone metabolism markers osteoprotegerin (OPG), C-terminal telopeptide (CTX1), and fibroblast growth factor 23 (FGF-23) were determined in the patients. Results The FRAX parameter was significantly lower (p < 0.001) in the obese men when compared to the controls. A significant negative correlation between FRAX and BMI (p < 0.001) was observed in the obese men, but not in the healthy subjects. There was also a negative correlation between FRAX and WC (p < 0.001), again only among the obese subjects. A positive correlation (p < 0.01) between FGF-23 and FRAX was found in the non-obese group. Conclusions Obese men have a lower 10-years fracture risk compared to the healthy controls. Additionally, the increased BMI and waist circumference in the obese men were found to be associated with a reduced bone fracture risk, whereas no similar relationship in controls was observed. Moreover, higher FGF-23 levels in the healthy males was correlated with an increased 10-year fracture risk.

Abstract Background Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting and disturbed vitamin D homeostasis as a result of the action of a phosphaturic protein – FGF-23, produced by a neoplasm. Although the clinical and biochemical profile of the syndrome is characteristic, it remains underreported and unrecognized by clinicians. Hyperparathyroidism is rarely associated with oncogenic osteomalacia, but it should be considered because of potentially life-threatening hypophosphatemia caused by both conditions. Case presentation We report a case of a 42-year-old woman admitted to the Department of Otolaryngology of the Military Institute of Medicine in Warsaw for the endoscopic resection of hormonally active glomangiopericytoma extending into the anterior skull base. She presented with a 5-year history of musculoskeletal pain and progressive weakness of the extremities which finally led her to become bedridden. After the excision of the tumor her symptoms and laboratory results gradually improved except increasing PTH serum levels. Further examination revealed a parathyroid proliferative tumor, which was surgically removed. The patient walked without aids at follow-up 16 months after the surgery. Conclusions This case is unusual because of tumor-induced osteomalacia and parathyroid adenoma occurring concomitantly. Further investigations of FGF-23 and PTH interplay should be conducted to elucidate the pathogenesis of hyperparathyroidism and tumorigenesis in some cases of TIO. By presenting this case, we wanted to remind clinicians of a rare and misdiagnosed paraneoplastic syndrome and highlight the importance of monitoring PTH concentrations during the follow-up of patients with TIO.

We report a case of tumour-induced osteomalacia in a 59-year-old man who presented with a long-standing history of myalgia, bone pain and pathological fracture of the bilateral femur at different intervals in the past 4 years. A biochemical evaluation revealed hypophosphatemia secondary to phosphaturia. Localization study by Ga-68 DOTANOC PET-CT for adult-onset hypophosphatemic osteomalacia revealed a tumour in the right femoral head. Resection of the tumour resulted in clinical improvement as well as normalization of biochemical parameters.

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.

Aims: The aim of this study was to find out the association between the Fibroblast Growth Factor-23 (FGF-23), Insulin-Like Growth Factor-1 (IGF-1), androgens, insulin resistance (IR), and bone mineral density (BMD) in patients with PCOS (Polycyctic Ovary Syndrome) and healthy controls is presented. Materials and Methods: The FGF-23, IGF-1, and Homeostatic Model Assessment for Insulin Resistance were evaluated in 47 patients with PCOS and 26 healthy females, and BMD was evaluated only in the PCOS group. Then these parameters were compared between groups, according to the presence of IR and hyperandrogenemia. Results: The mean FGF-23 was 137.55± 75.42 and 414.81 ± 53.02 (pg/ml), and mean IGF-1 was 28.41 ± 99.69 and 244.26 ± 58.99 (ng/ml) in patients with PCOS and healthy controls, respectively. In PCOS group, the FGF-23 was more significantly decreased in those with IR and amenorrheic. DEXA scores were found to be similar in PCOS group in terms of hyperandrogenemia and IR. Conclusions: Our results revealed that FGF-23 levels decreased in patients with PCOS, which was particularly significant in patients with IR. According to our findings; the low level of FGF-23 in the PCOS group with IR suggests that this marker may also be associated with the complications of PCOS, but to clarify this hypothesis, this marker needs to be investigated. [ABSTRACT FROM AUTHOR]

Background: X-linked hypophosphatemic rickets (XLH) is the most common cause of inherited rickets. Historically, XLH was treated with oral phosphate and calcitriol (conventional treatment). Burosumab, a fibroblast growth factor 23 (FGF-23) monoclonal antibody, was approved by the United States Food and Drug Administration (FDA) in 2018 for XLH treatment. Nevertheless, conventional treatment of XLH continues to be recommended by some specialists due to lack of published experience with burosumab in the clinical setting. We compared laboratory and radiographic changes observed following transition from conventional therapy to burosumab in pediatric XLH patients as part of routine care. Methods: This retrospective single-center study identified and retroactively studied twelve patients aged 1–18 years old with XLH previously treated with conventional therapy and transitioned to burosumab. Laboratory studies and radiographs were obtained routinely as standard of care during two treatment periods: (1) conventional therapy and (2) burosumab treatment. Laboratory values and radiologic rickets severity scores were compared between periods. Results: All laboratory values demonstrated improvement following 1 month of burosumab treatment, findings which were sustained over the 2-year study period. Rickets severity scores and height z-scores also improved with burosumab. There were no serious adverse events with burosumab, and adverse events overall were very infrequent and mild. One patient developed an asymptomatic mild elevation of serum phosphate while taking burosumab resulting in a temporary pause in therapy. Conclusions: Safety and effectiveness of burosumab in treatment of XLH were demonstrated as burosumab yielded statistically significant improvement in laboratory and radiographic markers of rickets and height compared to conventional therapy. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Phosphorus, present as phosphate in biological systems, is an essential mineral for various biological activities and biochemical processes. Numerous studies have indicated that disturbed phosphate balance may contribute to the development of metabolic syndrome (MetS). However, no consistent result was found on the association between phosphorus intake and serum phosphate concentration with MetS. It is believed that both positive and negative impacts of phosphorus/phosphate co-exist in parallel during MetS condition. Reduced phosphate level contributed to the development of obesity and hyperglycaemia. Low phosphate is believed to compromise energy production, reduce exercise capacity, increase food ingestion, and impair glucose metabolism. On the other hand, the effects of phosphorus/phosphate on hypertension are rather complex depending on the source of phosphorus and subjects' health conditions. Phosphorus excess activates sympathetic nervous system, renin-angiotensin-aldosterone system, and induces hormonal changes under pathological conditions, contributing to the blood pressure-rising effects. For lipid metabolism, adequate phosphate content ensures a balanced lipid profile through regulation of fatty acid biosynthesis, oxidation, and bile acid excretion. In conclusion, phosphate metabolism serves as a potential key feature for the development and progression of MetS. Dietary phosphorus and serum phosphate level should be under close monitoring for the management of MetS. [ABSTRACT FROM AUTHOR]

Background: Phosphaturic mesenchymal tumor (PMT) is a very rare tumor of bone and soft tissue that has no specific clinical manifestations. Here we present 2 cases of PMT in the right thigh, including comparatively adequate immunohistochemistry. Case Presentation: We described 2 cases of PMT in the right thigh with manifestations of hypophosphatemia. PET-CT examination showed that both patients had lesions with increased expression of somatostatin receptors in the right thigh. Bland cells and dirty calcified stroma were exhibited under the microscope. And immunohistochemical detection of FGF-23 was positive. Conclusions: PMT is a very uncommon tumor for which diagnosis and treatment are often delayed. Considering the importance of surgery for the treatment of this disease, a full understanding of its clinicopathological features will facilitate the diagnosis of this disease. [ABSTRACT FROM AUTHOR]

Aim/Purpose: -Type 2 Diabetes Mellitus affecting around major population around the world and with increasing ratio in near future. There is modification in tissue cells which fails to respond to insulin properly.(FGF-23) Fibroblast Growth Factor-23 known as a hormone composed of peptides circulating in blood synthesized by (osteoblast) bone cells. FGF-23 can exhibit physiological functions in conjugation to bone metabolism like bone calcification and hematopoiesis. An important nutrient of osteoblast cells has been a glucose and also many studies have shown significant alteration of bone formation in increased glucose level. Hyperglycemia affects bone remodeling in cells of bones, insulin signalinginteraction and metabolism of bones through insulin receptors directly or indirectly. Hence, this study is designed to estimate levels of FGF-23 in bone metabolism among healthy group, prediabetic and in people suffering from type-2 diabetes mellitus. Methods: -The type of present study is observational and is designed as a case control study performed in hospital. Total of 225 volunteers were taken in control group, prediabetes and 75 diabetes mellitus type 2patients. Standard deviation and was analyzed using one-way ANOVA test and for further analysis for specific differences between 3 groups with post-hoc tukey test. Values of P<0.05 was taken as significant. Results: -Our results shows positive relationship for the parameters tested when found between the groups using test known as posthoc tukey (p<0.001). Conclusion: -The present study gives clear insight about bone remodeling and bone formation when controlled by FGF-23 hormone and can be predicted as biological possible bio-marker in the bone metabolism. Henceforth, more advanced studies are required for detailed examination of FGF-23 physiological actions on bone metabolism and its inter-relationship with insulin resistance especially diabetic patients. [ABSTRACT FROM AUTHOR]