scholarly journals A phosphate and calcium-enriched diet promotes progression of 5/6-nephrectomy-induced chronic kidney disease in C57BL/6 mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Radloff ◽  
N. Latic ◽  
U. Pfeiffenberger ◽  
C. Schüler ◽  
S. Tangermann ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Phosphate ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Time Course ◽  
Bone Mineralization ◽  
Fibroblast Growth Factor 23 ◽  
Functional Decline ◽  
Left Ventricular ◽  
Normal Diet

AbstractC57BL/6 mice are known to be rather resistant to the induction of experimental chronic kidney disease (CKD) by 5/6-nephrectomy (5/6-Nx). Here, we sought to characterize the development of CKD and its cardiac and skeletal sequelae during the first three months after 5/6-Nx in C57BL/6 mice fed a calcium- and phosphate enriched diet (CPD) with a balanced calcium/phosphate ratio. 5/6-NX mice on CPD showed increased renal fibrosis and a more pronounced decrease in glomerular filtration rate when compared to 5/6-Nx mice on normal diet (ND). Interestingly, despite comparable levels of serum calcium, phosphate, and parathyroid hormone (PTH), circulating intact fibroblast growth factor-23 (FGF23) was 5 times higher in 5/6-Nx mice on CPD, relative to 5/6-Nx mice on ND. A time course experiment revealed that 5/6-Nx mice on CPD developed progressive renal functional decline, renal fibrosis, cortical bone loss, impaired bone mineralization as well as hypertension, but not left ventricular hypertrophy. Collectively, our data show that the resistance of C57BL/6 mice to 5/6-Nx can be partially overcome by feeding the CPD, and that the CPD induces a profound, PTH-independent increase in FGF23 in 5/6-Nx mice, making it an interesting tool to assess the pathophysiological significance of FGF23 in CKD.

scholarly journals Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Guillaume Courbon ◽  
Connor Francis ◽  
Claire Gerber ◽  
Samantha Neuburg ◽  
Xueyan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Lipocalin 2

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3–5

2020 ◽  
Author(s):  
Anne Schön ◽  
Maren Leifheit-Nestler ◽  
Jennifer Deppe ◽  
Dagmar-Christiane Fischer ◽  
Aysun K Bayazit ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Cardiac Remodelling ◽  
Study Cohort ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Cardiac Phenotype

Abstract Background Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin–angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear. Methods In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case–control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3–5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months. Results In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups. Conclusions Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3–5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.

scholarly journals Cardiovascular Risk Factors and Chronic Kidney Disease—FGF23: A Key Molecule in the Cardiovascular Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Rika Jimbo ◽  
Tatsuo Shimosawa
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Cardiovascular Risks ◽  
Mineral And Bone Disorder ◽  
Promising Target ◽  
Increased Risk

Patients with chronic kidney disease (CKD) are at increased risk of mortality, mainly from cardiovascular disease. Moreover, abnormal mineral and bone metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our understanding of CKD-MBD and has revealed more complex cross-talk and endocrine feedback loops between the kidney, parathyroid gland, intestines, and bone. During the past decade, reports of clinical studies have described the association between FGF23 and cardiovascular risks, left ventricular hypertrophy, and vascular calcification. Recent translational reports have described the existence of FGF23-Klotho axis in the vasculature and the causative effect of FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising target for novel therapeutic approaches to improve clinical outcomes of CKD patients.

scholarly journals Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease

Circulation ◽  
2009 ◽  
Vol 119 (19) ◽  
pp. 2545-2552 ◽  
Author(s):  
Orlando M. Gutiérrez ◽  
James L. Januzzi ◽  
Tamara Isakova ◽  
Karen Laliberte ◽  
Kelsey Smith ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Left Ventricular Hypertrophy ◽  
Fibroblast Growth Factor ◽  
Ventricular Hypertrophy ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth

Role fibroblast growth factor-23 (FGF-23) in developmently of cardiorenal outcomes in chronic kidney disease stages III-V

2014 ◽  
Vol 20 (30) ◽  
pp. 36-41
Author(s):  
Дзгоева ◽  
Fatima Dzgoeva ◽  
Бестаева ◽  
Tamara Bestaeva ◽  
Сопоев ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Left Ventricular Geometry ◽  
Fibroblast Growth ◽  
Fgf 23 ◽  
Disease Stages

The aim of our study was to investigate the association of fibroblast growth factor 23 (FGF-23) with сardiorenal outcomes in chronic kidney disease stages III-V. FGF-23 was measured using commercially kits in 83 CKD stages III-V patients (40 females and 43 males aged 37-68 years). The patients were examined clinically with estimation of the levels of parathormone, calcium, phosphorus. Echocardiography on Aloka-4000 unit was made. Left ventricular geometry was assessed by J.Gottdiener classification. Therapeutic policy aimed of correction of anemia, arterial hypertension and phosphorus-calcium metabolism. FGF-23 correlated with renal function and weight of left ventricular hypertrophy. We have shown that changes in bone mediator and phosphate metabolism induced by CKD are independently associated with сardiorenal dysfunction.

scholarly journals Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease—A Pediatric Perspective

2021 ◽  
Vol 9 ◽  
Author(s):  
Andrea Grund ◽  
Manish D. Sinha ◽  
Dieter Haffner ◽  
Maren Leifheit-Nestler
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Left Ventricular Hypertrophy ◽  
Fibroblast Growth Factor ◽  
Ventricular Hypertrophy ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Hypertrophic Growth

Cardiovascular diseases (CVD) are a hallmark in pediatric patients with chronic kidney disease (CKD) contributing to an enhanced risk of all-cause and CV morbidity and mortality in these patients. The bone-derived phosphaturic hormone fibroblast growth factor (FGF) 23 progressively rises with declining kidney function to maintain phosphate homeostasis, with up to 1,000-fold increase in patients with kidney failure requiring dialysis. FGF23 is associated with the development of left ventricular hypertrophy (LVH) and thereby accounts to be a CVD risk factor in CKD. Experimentally, FGF23 directly induces hypertrophic growth of cardiac myocytes in vitro and LVH in vivo. Further, clinical studies in adult CKD have observed cardiotoxicity associated with FGF23. Data regarding prevalence and determinants of FGF23 excess in children with CKD are limited. This review summarizes current data and discusses whether FGF23 may be a key driver of LVH in pediatric CKD.

scholarly journals Changes of FGF23 and the Renin-Angiotensin-System in Male Mouse Models of Chronic Kidney Disease and Cardiac Hypertrophy

2021 ◽  
Author(s):  
Kohei Okamoto ◽  
Hideki Fujii ◽  
Kentaro Watanabe ◽  
Shunsuke Goto ◽  
Keiji Kono ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Renin Angiotensin System ◽  
Close Correlation ◽  
Left Ventricular ◽  
Heart Weight ◽  
Related Factors ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Abstract Serum fibroblast growth factor 23 (FGF23) levels and the renin-angiotensin-aldosterone system (RAAS) are elevated in chronic kidney disease (CKD) patients, and their association with left ventricular hypertrophy (LVH) has been reported. However, whether the FGF23 elevation is the cause or result of LVH remains unclear. At 10 weeks, male C57BL/6J mice were divided into four groups: Sham, CKD (5/6 nephrectomy), LVH (transaortic constriction), and CKD/LVH group. At 16 weeks, the mice were sacrificed, and blood and urine, cardiac expressions of FGF23 and RAAS-related factors, and cardiac histological analyses were performed. Heart weight, serum FGF23 levels, and cardiac expression of FGF23 and RAAS-related factors, except for angiotensin-converting enzyme 2, more increased in the CKD/LVH group compared to the other groups. A significant correlation between LVH and cardiac expressions of FGF23 and RAAS-related factors was observed. Furthermore, there was a significantly close correlation of the cardiac expression of FGF23 with LVH and RAAS-related factors. The coexisting CKD and LVH increased serum and cardiac FGF23 and RAAS-related factors, and there was a significant correlation between them. A close correlation of cardiac, but not serum FGF23, with LVH and RAAS suggested that local FGF23 levels may be associated with LVH and RAAS activation.

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