scholarly journals FGF23 and Phosphate–Cardiovascular Toxins in CKD

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 647 ◽  
Author(s):  
Vogt ◽  
Leifheit-Nestler
Keyword(s):  
Kidney Disease ◽  
Vascular Calcification ◽  
Ventricular Hypertrophy ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Serum Phosphate ◽  
Cardiovascular Outcome ◽  
Therapeutic Interventions ◽  
Direct Targeting ◽  
End Stage

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients.

Cardiorenal Syndrome in End-Stage Kidney Disease

2015 ◽  
Vol 40 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Kazuhiko Tsuruya ◽  
Masahiro Eriguchi ◽  
Shunsuke Yamada ◽  
Hideki Hirakata ◽  
Takanari Kitazono
Keyword(s):  
Risk Factor ◽  
Kidney Disease ◽  
Chronic Inflammation ◽  
Vascular Calcification ◽  
Fibroblast Growth Factor 23 ◽  
Cardiorenal Syndrome ◽  
End Stage Kidney Disease ◽  
Mineral And Bone Disorder ◽  
End Stage ◽  
Mia Syndrome

Background: Cardiorenal syndrome (CRS) in patients with end-stage kidney disease (ESKD) represents mainly cardiovascular disease (CVD) due to various complications associated with renal dysfunction—defined as type 4 CRS by Ronco et al.—because the effect of cardiac dysfunction on the kidneys does not need to be taken into consideration, unlike in non-dialysis dependent chronic kidney disease (CKD). Summary: Patients with ESKD are often in a state of chronic inflammation due to the upregulation of proinflammatory cytokines. Chronic inflammation leads to malnutrition and consequently to vascular endothelial dysfunction and vascular calcification, which is referred to as malnutrition-inflammation-atherosclerosis (MIA) syndrome and acts as a major risk factor for CVD. Anemia also plays a crucial role in CVD, and individuals with erythropoietin-resistant anemia have a particularly high risk of CVD. However, caution is emphasized because not only anemia itself, but also the overtreatment of anemia with erythropoiesis-stimulating agents aimed at elevating hemoglobin to ≥13 g/dl can also increase the risk of CVD. In CKD-mineral and bone disorder (CKD-MBD), phosphate load triggers the interactions between various factors such as calcium, parathyroid hormone, vitamin D, and fibroblast growth factor 23, promoting vascular calcification and thus becoming a risk factor for CVD. Key Messages: In addition to traditional atherosclerosis risk factors such as hypertension, diabetes, and dyslipidemia, the involvement of MIA syndrome, anemia, and CKD-MBD accompanying CKD have also become a focus for investigation as major players in CRS in patients with ESKD.

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

scholarly journals Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sinee Disthabanchong
Keyword(s):  
Vascular Calcification ◽  
Early Stage ◽  
Subclinical Atherosclerosis ◽  
Fibroblast Growth Factor 23 ◽  
Left Ventricular ◽  
Normal Serum ◽  
Serum Phosphate ◽  
Calciprotein Particles ◽  
Habitual Intake ◽  
Fgf 23

Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23) which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs) causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs). In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.

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.

Updated mechanisms of calcification of cardiovascular system and its correction in chronic kidney disease

2020 ◽  
Vol 24 (5) ◽  
pp. 18-28
Author(s):  
F. U. Dzgoeva ◽  
O. V. Remizov ◽  
V. G. Goloeva ◽  
Z. R. Ikoeva
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Aortic Pulse Wave Velocity ◽  
Left Ventricular ◽  
Elastic Fibers ◽  
Protein Energy Wasting ◽  
Therapeutic Goals

In chronic kidney disease (CKD), progressive decline in kidney function leads to disorders of mineral metabolism, which are usually called secondary hyperparathyroidism. An increase in the serum concentration of the parathyroid hormone is associ­ated with a decrease in the level of calcium and calcitriol and/or an increase in the level of fibroblast growth factor-23 and inorganic phosphate in serum. CKD-related disorders of mineral and bone metabolism are associated with other metabolic disorders, such as acidosis, protein-energy wasting, inflammation, and accumulation of uremic toxins. This contributes to vascular calcification, which is a consequence of an imbalance between numerous inhibitors and promoters of soft tissue min­eralization. Vascular calcification is a degenerative process characterized by the accumulation of calcium and phosphate salts in the artery wall. This is observed in almost all vascular areas and can develop in the media, intima, or both vascular layers of the arteries. Calcification of the intima usually occurs due to atherosclerosis and may be responsible for coronary ischemic events. Conversely, media calcification is non-exclusive and predominantly develops along elastic fibers. As a result, media calcification increases vascular stiffness, aortic pulse wave velocity, systolic and pulse blood pressure, contributing to the de­velopment of left ventricular hypertrophy and heart failure. This review examines the current understanding of the mechanisms that lead to the development of vascular calcification in CKD. The participation of factors such as inflammation, age glycation end products, indoxyl sulfate, and others in calcification processes is discussed. Promising therapeutic goals associated with a new understanding of the mechanisms of cardiovascular calcification in CKD are identified.

Sign in / Sign up

Export Citation Format

Share Document