scholarly journals Clinical Significance of FGF-23 in Patients with CKD

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Domenico Russo ◽  
Yuri Battaglia
Keyword(s):  
Ventricular Hypertrophy ◽  
Vascular Dysfunction ◽  
Left Ventricular ◽  
Vitamin D Metabolism ◽  
Fgf Receptor ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Phosphate Retention ◽  
Fgf 23

FGF23 is a bone-derived hormone that plays an important role in the regulation of phosphate and 1,25-dihydroxy vitamin D metabolism. FGF23 principally acts in the kidney to induce urinary phosphate excretion and suppress 1,25-dihydroxyvitamin D synthesis in the presence of FGF receptor 1 (FGFR1) and its coreceptor Klotho. In patients with chronic kidney disease (CKD), circulating FGF23 levels are progressively increased to compensate for persistent phosphate retention, but this results in reduced renal production of 1,25-dihydroxyvitamin D and leads to hypersecretion of parathyroid hormone. Furthermore, FGF23 is associated with vascular dysfunction, atherosclerosis, and left ventricular hypertrophy. This paper summarizes the role of FGF23 in the pathogenesis of mineral, bone, and cadiovascular disorders in CKD.

Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems

2005 ◽  
Vol 288 (1) ◽  
pp. E125-E132 ◽  
Author(s):  
Wei Xiang ◽  
Juan Kong ◽  
Songcang Chen ◽  
Li-Ping Cao ◽  
Guilin Qiao ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cardiac Hypertrophy ◽  
Vitamin D Receptor ◽  
Mrna Level ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Renin Angiotensin ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angiotensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D3 regulates cardiac functions, at least in part, through the RAS.

Abstract 313: STIM1 Silencing Reverses Pressure-overload Induced Cardiac Hypertrophy In Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ludovic O Bénard ◽  
Daniel S Matasic ◽  
Mathilde Keck ◽  
Anne-Marie Lompré ◽  
Roger J Hajjar ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Aortic Banding ◽  
Cross Section Area ◽  
Abdominal Aortic ◽  
Section Area

STromal Interaction Molecule 1 (STIM1), a membrane protein of the sarcoplasmic reticulum, has recently been proposed as a positive regulator of cardiomyocyte growth by promoting Ca2+ entry through the plasma membrane and the activation of Ca2+-mediated signaling pathways. We demonstrated that STIM1 silencing prevented the development of left ventricular hypertrophy (LVH) in rats after abdominal aortic banding. Our aim was to study the role of STIM1 during the transition from LVH to heart failure (HF). For experimental timeline, see figure. Transverse Aortic Constriction (TAC) was performed in C57Bl/6 mice. In vivo gene silencing was performed using recombinant Associated AdenoVirus 9 (AAV9). Mice were injected with saline or with AAV9 expressing shRNA control or against STIM1 (shSTIM1) (dose: 1e+11 viral genome), which decreased STIM1 cardiac expression by 70% compared to control. While cardiac parameters were similar between the TAC groups at weeks 3 and 6, shSTIM1 animals displayed a progressive and total reversion of LVH with LV walls thickness returning to values observed in sham mice at week 8. This reversion was associated with the development of significant LV dilation and severe contractile dysfunction, as assessed by echography. Hemodynamic analysis confirmed the altered contractile function and dilation of shSTIM1 animals. Immunohistochemistry showed a trend to more fibrosis. Despite hypertrophic stimuli, there was a significant reduction in cardiac myocytes cross-section area in shSTIM1-treated animals as compared to other TAC mice. This study showed that STIM1 is essential to maintain compensatory LVH and that its silencing accelerates the transition to HF.

Correlation between Hypervolemia, Left Ventricular Hypertrophy and Fibroblast Growth Factor- 23 in Prevalent Hemodialysis Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sahar Mahmoud Shawky ◽  
Mohamed Saeed Hassan ◽  
Maha Mohamed Khalifa ◽  
Kholoud Mahmoud Amin
Keyword(s):  
Weight Gain ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Volume Overload ◽  
Hemodialysis Patients ◽  
Left Ventricular ◽  
Bone Diseases ◽  
Interdialytic Weight Gain ◽  
Fgf 23 ◽  
Esrd Patients

Abstract Background Patients with end-stage renal disease are exposed to extreme volume shifts and thereby cardiovascular strain as a consequence of interdialytic weight gain, fluid removal during hemodialysis and also chronic fluid overload. In long-term hemodialysis patients, higher IDWG (interdialytic weight gain) is associated with poor survival and increased cardiovascular death. Patients with the lowest interdialytic fluid retention have the greatest survival. It was found that increased interdialytic volume load is associated with increased both LVMI and FGF-23 level. Objective To evaluate correlation between hypervolemia, left ventricular hypertrophy and FGF-23 in prevalent hemodialysis patients. Patients and Methods This cross sectional study was conducted in Ain shams university hospital and Al Agoza hospital, on 60 prevalent hemodialysis patients.Three patient died during the study. Results FGF-23 had a positive correlation with (weight gain, (PO4)3-, PTH, IVS, PW and LVMI). Conclusion FGF-23 might be a marker of volume overload and LVH in ESRD patients, as it positively correlated with (weight gain, IVS, PW and LVMI). FGF-23 is a marker of bone diseases, as it positively correlated with (PO4)3- and PTH. Volume overload has a negative impact on morbidity and mortality in ESRD patients.

Role of Calcineurin-Dependent Signaling Pathway on the Left Ventricular Hypertrophy Induced by Pressure Overload

2001 ◽  
Vol 31 (11) ◽  
pp. 1159
Author(s):  
Hainan Piao ◽  
Jin Sook Kwon ◽  
Hye Young Lee ◽  
Tae Jin Youn ◽  
Dong Woon Kim ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Signaling Pathway ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Dependent Signaling Pathway

scholarly journals Central role of the proximal tubular αKlotho/FGF receptor complex in FGF23-regulated phosphate and vitamin D metabolism

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ai Takeshita ◽  
Kazuki Kawakami ◽  
Kenryo Furushima ◽  
Masayasu Miyajima ◽  
Kazushige Sakaguchi
Keyword(s):  
Vitamin D ◽  
Receptor Complex ◽  
Vitamin D Metabolism ◽  
Fgf Receptor ◽  
Proximal Tubular

scholarly journals Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chih-Huang Li ◽  
Xiaolei Tang ◽  
Samiksha Wasnik ◽  
Xiaohua Wang ◽  
Jintao Zhang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Vitamin D ◽  
Growth Factor ◽  
Kidney Failure ◽  
Mechanistic Study ◽  
Blood Levels ◽  
Biological Functions ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Fgf 23

Abstract Background Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. Methods We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. Results We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. Conclusions Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

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