The Complexity of FGF23 Effects on Cardiomyocytes in Normal and Uremic Milieu

Figurek, Andreja; Rroji, Merita; Spasovski, Goce

doi:10.3390/cells10051266

Cited by 6 publications

(5 citation statements)

References 111 publications

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“…Previous data have shown that high FGF23 titers are associated with increased rates of cardiovascular events in CKD patients [ 13 , 20 , 21 ] and the general population [ 22 ]. FGF23 has deleterious cardiovascular effects, including cardiac hypertrophy [ 23 , 24 , 25 ], arterial wall calcification, and alteration of intracellular calcium and smooth muscle cell contractility [ 26 ]. There is currently limited evidence concerning the potential mechanisms related to the association of high baseline FGF23 levels and increased risk of severe infections.…”

Section: Discussionmentioning

confidence: 99%

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort

Toro

Michea

Parra-Lucares

et al. 2023

Toxins

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End-stage renal disease (ESRD) patients are a population with high rates of COVID-19 and mortality. These patients present a low response to anti-SARS-CoV-2 immunization, which is associated with immune dysfunction. ESRD patients also present high plasma titers of Fibroblast Growth Factor 23 (FGF23), a protein hormone that reduces immune response in vivo and in vitro. Increased FGF23 levels associate with higher infection-related hospitalizations and adverse infectious outcomes. Thus, we evaluated whether ESRD patients with high FGF23 titers have an increased rate of SARS-CoV-2 infection. Methods: We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. Results: We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03–3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. Discussion: Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

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Section: Discussionmentioning

confidence: 99%

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort

Toro

Michea

Parra-Lucares

et al. 2023

Toxins

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“…FGF23 is a potent phosphaturic glycoprotein secreted by osteoblasts and osteocytes, which express its endocrine hormone effect by binding to the fibroblastic growth receptor and coreceptor klotho. Whereas FGFRs are abundantly expressed throughout the body, tissue presentation of a Klotho is tightly handled and thus selects the effect of FGF23 on target organs [35]. In addition, the increase in FGF23 diminishes phosphate absorption in the gut by inhibiting NaPi-2b expression and suppressing circulating calcitriol.…”

Section: Phosphate Homeostasis In the Physiological Milieu And Ckdmentioning

confidence: 99%

Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease

Rroji

Figurek

Viggiano

et al. 2022

IJMS

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The nervous system and the kidneys are linked under physiological states to maintain normal body homeostasis. In chronic kidney disease (CKD), damaged kidneys can impair the central nervous system, including cerebrovascular disease and cognitive impairment (CI). Recently, kidney disease has been proposed as a new modifiable risk factor for dementia. It is reported that uremic toxins may have direct neurotoxic (astrocyte activation and neuronal death) and/or indirect action through vascular effects (cerebral endothelial dysfunction, calcification, and inflammation). This review summarizes the evidence from research investigating the pathophysiological effects of phosphate toxicity in the nervous system, raising the question of whether the control of hyperphosphatemia in CKD would lower patients’ risk of developing cognitive impairment and dementia.

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“…Маркером активації фібробластів виступає фактор росту фібробластів-23, який, за даними деяких авторів, через трансформуючий фактор росту бета (Transforming growth factor beta, TGFβ)білок представник цитокінів, здатний призводити до нерегульованих змін у сигнальному шляху TGFβ і спричиняти ряд ускладнень, зокрема апоптоз, блокування активації макрофагів і лімфоцитів, регуляції клітинного циклу і, в тому числі, викликати фіброз тканин. Таким чином, у тканині запального міокарду FGF-23 сприяє активації фібробластів за допомогою однієї з ізоформтрансформуючого фоктора росту бета 1 (TGFβ1), перетворюючи фібробласти в міофібробласти за допомогою сигнального шляху fibroblast growth factor receptor 1 (FGFR1) [3,6,9].…”

Section: матеріали та методиunclassified

Clinical, laboratory changes and fibroblast growth factor in patients with myocarditis

Myndziv¹,

Yarema²

2022

Rep. of Vinnytsia Nation. Med. Univ.

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Annotation. The relevance of the problem of diagnosis and treatment of myocarditis in the world and in Ukraine is growing. The prevalence of myocarditis is up to 20% of all non-coronary heart lesions. According to the results of the study of the sudden death causes in young people, the detection of inflammatory lesions of the myocardium varies in the range of 2-42%. The article analyzes the course of acute myocarditis of unknown etiology in 48 adult patients (31 patients with a moderate-severe course and 17 patients with a severe course), establishes clinical features of the course of the disease and laboratory markers associated with the severity of the course of the disease and myocardial fibrosis. The severity of the course of the disease was determined based on the volume of myocardial damage, the stage and functional class (FC) of heart failure, the presence of systolic heart dysfunction and life-threatening rhythm and conduction disorders. Statistical processing of the research results was carried out using the created database of examined patients in the StatSoft Statistica v 10.0 program, with a known number of observations (n). The Mann-Whitney test was used to determine differences between quantitative traits. Spearman's rank correlation coefficient was calculated to determine the degree of statistical dependence between indicators. It was established that myocarditis mostly had a course of moderate severity (64,6 %) with the presence of heart failure of II A stage in 54,8 % of inspected patients, and was accompanied by combined complex rhythm and conduction disorders in 38,7 % of patients. A reliable correlation was established between the increase in markers of inflammation (CRP, fibrinogen), cardiomyocyte lysis (CFC-MV) and fibroblast growth factor 23 (FGF-23), which indicates an increase in profibrotic processes as a result of myocardium inflammatory damage. It is important to carry out a detailed study of the clinical features of myocarditis with the further perspective of developing diagnostic methods for timely etiopathogenetic treatment and forecasting the adverse course of the disease.

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The Complexity of FGF23 Effects on Cardiomyocytes in Normal and Uremic Milieu

Cited by 6 publications

References 111 publications

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort

Phosphate in the Context of Cognitive Impairment and Other Neurological Disorders Occurrence in Chronic Kidney Disease

Clinical, laboratory changes and fibroblast growth factor in patients with myocarditis

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