scholarly journals Increased fibroblast growth factor-21 in chronic kidney disease is a trade-off between survival benefit and blood pressure dysregulation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Toshihiro Nakano ◽  
Kazuhiro Shiizaki ◽  
Yutaka Miura ◽  
Masahiro Matsui ◽  
Keisei Kosaki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Nervous System ◽  
Growth Factor ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Wild Type ◽  
Sympathetic Nervous

AbstractCirculating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21−/− mice died earlier than wild-type mice. Paradoxically, these Fgf21−/− CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21−/− CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.

scholarly journals Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2470-2481 ◽  
Author(s):  
Nicholas Douris ◽  
Darko M. Stevanovic ◽  
ffolliott M. Fisher ◽  
Theodore I. Cisu ◽  
Melissa J. Chee ◽  
...  
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Sympathetic Nervous System ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Male Mice ◽  
Sympathetic Nervous ◽  
The Brain

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

scholarly journals Contribution of Selected Vasoactive Systems to Blood Pressure Regulation in Two Models of Chronic Kidney Disease

2020 ◽  
pp. 405-414
Author(s):  
N DRÁBKOVÁ ◽  
S HOJNÁ ◽  
J ZICHA ◽  
I VANĚČKOVÁ
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Nervous System ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Renal Artery ◽  
Partial Nephrectomy ◽  
Wistar Rats ◽  
Sympathetic Nervous

It is generally accepted that angiotensin II plays an important role in high blood pressure (BP) development in both 2-kidney-1-clip (2K1C) Goldblatt hypertension and in partial nephrectomy (NX) model of chronic kidney disease (CKD). The contribution of sympathetic nervous system and nitric oxide to BP control in these models is less clear. Partial nephrectomy or stenosis of the renal artery was performed in adult (10-week-old) male hypertensive heterozygous Ren-2 transgenic rats (TGR) and normotensive control Hannover Sprague Dawley (HanSD) rats and in Wistar rats. One and four weeks after the surgery, basal blood pressure (BP) and acute BP responses to the consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats. Both surgical procedures increased plasma urea, a marker of renal damage; the effect being more pronounced following partial nephrectomy in hypertensive TGR than in normotensive HanSD rats with a substantially smaller effect in Wistar rats after renal artery stenosis. We demonstrated that the renin-angiotensin system does not play so fundamental role in blood pressure maintenance during hypertension development in either CKD model. By contrast, a more important role is exerted by the sympathetic nervous system, the activity of which is increased in hypertensive TGR-NX in the developmental phase of hypertension, while in HanSD-NX or Wistar-2K1C it is postponed to the established phase. The contribution of the vasoconstrictor systems (RAS and SNS) was increased following hypertension induction. The role of NO-dependent vasodilation was unchanged in 5/6 NX HanSD and in 2K1C Wistar rats, while it gradually decreased in 5/6 NX TGR rats.

scholarly journals Cardiovascular Risk in Chronic Kidney Disease: Role of the Sympathetic Nervous System

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jeanie Park
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Nervous System ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Renal Disease ◽  
Left Ventricular ◽  
Sympathetic Nervous

Patients with chronic kidney disease are at significantly increased risk for cardiovascular disease and sudden cardiac death. One mechanism underlying increased cardiovascular risk in patients with renal failure includes overactivation of the sympathetic nervous system (SNS). Multiple human and animal studies have shown that central sympathetic outflow is chronically elevated in patients with both end-stage renal disease (ESRD) and chronic kidney disease (CKD). SNS overactivation, in turn, increases the risk of cardiovascular disease and sudden death by increasing arterial blood pressure, arrythmogenicity, left ventricular hypertrophy, and coronary vasoconstriction and contributes to the progression renal disease. This paper will examine the evidence for SNS overactivation in renal failure from both human and experimental studies and discuss mechanisms of SNS overactivity in CKD and therapeutic implications.

scholarly journals Fibroblast growth factor 21 in chronic kidney disease

2018 ◽  
Vol 32 (3) ◽  
pp. 365-377 ◽  
Author(s):  
Paulo Giovanni de Albuquerque Suassuna ◽  
Rogério Baumgratz de Paula ◽  
Hélady Sanders-Pinheiro ◽  
Orson W. Moe ◽  
Ming-Chang Hu
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

scholarly journals SYMPATHETIC HYPERACTIVITY IN CHRONIC KIDNEY DISEASE PATIENTS: FROM PATHOGENESIS TO TREATMENT

2017 ◽  
pp. 141-160
Author(s):  
N. Stepanova
Keyword(s):  
Chronic Kidney Disease ◽  
Nervous System ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Crucial Role ◽  
Clinical Relevance ◽  
Cardiovascular Complications ◽  
Current Treatment ◽  
Sympathetic Hyperactivity ◽  
Sympathetic Nervous

Sympathetic nervous system plays a crucial role in the development of cardiovascular complications in chronic kidney disease (CKD) patients. The aim of this review is to summarize up-to-date knowledge of the sympathetic hyperactivity in the pathogenesis of CKD, its clinical relevance, and as the options of current treatment.

scholarly journals Regulation and Potential Biological Role of Fibroblast Growth Factor 21 in Chronic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue Zhou ◽  
Yuefeng Zhang ◽  
Ning Wang
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Biological Function ◽  
Vital Role ◽  
Biological Role ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Fgf Receptor

Chronic kidney disease (CKD) is an incurable progressive disease with the progressive impairment of kidney function, which can accelerate the progression of cardiovascular disease, increase the risk of infection, and lead to related complications such as anemia and bone disease. CKD is to a great extent preventable and treatable, and it is particularly important to improve the early diagnosis, strengthen the research underlying the mechanism of disease occurrence and development, and innovate new intervention measures. Fibroblast growth factor 21 (FGF21) belongs to one of members of endocrine FGF subfamily with evolutionarily conserved functions and performs a vital role in the regulation of energy balance and adipose metabolism. FGF21 needs to rely on β-Klotho protein to specifically bind to FGF receptor (FGFR), which activates the FGF21 signaling exerting the biological function. FGF21 is deemed as an important regulatory factor extensively modulating many cellular functions under physiologic and pathologic conditions. Although the metabolic effect of FGF21 has been extensively studied, its potential biological role in the kidney has not been generally investigated. In this review, we summarize the biological characteristics, regulation and biological function of FGF21 based on the current studies, and briefly discuss the potential relationship with chronic kidney disease.

The Sympathetic Nervous System in Chronic Kidney Disease

2013 ◽  
Vol 15 (4) ◽  
pp. 370-376 ◽  
Author(s):  
Sebastian Ewen ◽  
Christian Ukena ◽  
Dominik Linz ◽  
Roland E. Schmieder ◽  
Michael Böhm ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Nervous System ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Sympathetic Nervous

scholarly journals Fibroblast growth factor 21 is associated with increased serum total antioxidant capacity and oxidized lipoproteins in humans with different stages of chronic kidney disease

2021 ◽  
Vol 12 ◽  
pp. 204201882110011
Author(s):  
Gómez-Sámano Miguel Ángel ◽  
Vargas-Abonce Valerie Paola ◽  
Martínez-Sánchez Froylan David ◽  
Palacios-Báez Lucía ◽  
Vera-Zertuche Juan Mauricio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Total Antioxidant ◽  
Male Sex

Background and aims: Oxidative stress (OS) induces the production of fibroblast growth factor 21 (FGF21). Previous data have revealed that FGF21 protects cells from OS injury and death, making it a potential therapeutic option for many diseases with increased OS. However, the association of this growth factor with OS markers in humans with chronic kidney disease (CKD) remains unknown. This study aims to evaluate the association of serum FGF21 with serum total antioxidant capacity (TAC) and oxidized low-density lipoproteins (OxLDL) in subjects in different stages of kidney disease. Methods: This is a cross-sectional study that included 382 subjects with different stages of CKD, irrespective of type 2 diabetes (T2D) diagnosis. Associations of serum FGF21 with OxLDL, TAC, sex, age, body mass index (BMI), fasting plasma glucose, estimated glomerular filtration rate (eGFR), T2D, and smoking, were evaluated through bivariate and partial correlation analyses. Independent associations of these variables with serum FGF21 were evaluated using multiple linear regression analysis. Results: Serum FGF21 was significantly and positively correlated with age ( r = 0.236), TAC (lnTAC) ( r = 0.217), and negatively correlated with eGFR ( r = −0.429) and male sex ( r = −0.102). After controlling by age, sex, BMI, T2D, smoking, and eGFR; both TAC and OxLDL were positively correlated with FGF21 ( r = 0.117 and 0.158 respectively, p < 0.05). Using multiple linear regression analysis, eGFR, male sex, T2D, OxLDL, and TAC were independently associated with serum FGF21 (STDβ = −0.475, 0.162, −0.153, 0.142 and 0.136 respectively; p < 0.05 for all) adjusted for age, BMI, smoking, and fasting plasma glucose. Conclusion: A positive association between serum FGF21 and OS has been found independently of renal function in humans. Results from the present study provide novel information for deeper understanding of the role of FGF21 in OS in humans with CKD and T2D; mechanistic studies to explain the association of serum FGF21 with oxidative stress in CKD are needed.

The Role of Sympathetic Nervous System in the Progression of Chronic Kidney Disease in the Era of Catheter Based Sympathetic Renal Denervation

2013 ◽  
Vol 8 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Dimitrios Petras ◽  
Konstantinos Koutroutsos ◽  
Athanasios Kordalis ◽  
Costas Tsioufis ◽  
Christodoulos Stefanadis
Keyword(s):  
Chronic Kidney Disease ◽  
Nervous System ◽  
Kidney Disease ◽  
Sympathetic Nervous System ◽  
Renal Denervation ◽  
Sympathetic Nervous
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