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.

Vascular calcification in chronic kidney disease

2010 ◽  
Vol 119 (3) ◽  
pp. 111-121 ◽  
Author(s):  
Adrian Covic ◽  
Mehmet Kanbay ◽  
Luminita Voroneanu ◽  
Faruk Turgut ◽  
Dragomir N. Serban ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Vascular Calcification ◽  
Mineral Metabolism ◽  
Left Ventricular ◽  
Arterial Calcification ◽  
Pathophysiological Mechanism ◽  
Cardiovascular Morbidity And Mortality

VC (vascular calcification) is highly prevalent in patients with CKD (chronic kidney disease), but its mechanism is multifactorial and incompletely understood. In addition to increased traditional risk factors, CKD patients also have a number of non-traditional cardiovascular risk factors, which may play a prominent role in the pathogenesis of arterial calcification, such as duration of dialysis and disorders of mineral metabolism. The transformation of vascular smooth muscle cells into chondrocytes or osteoblast-like cells seems to be a key element in VC pathogenesis, in the context of passive calcium and phosphate deposition due to abnormal bone metabolism and impaired renal excretion. The process may be favoured by the low levels of circulating and locally produced VC inhibitors. VC determines increased arterial stiffness, left ventricular hypertrophy, a decrease in coronary artery perfusion, myocardial ischaemia and increased cardiovascular morbidity and mortality. Although current therapeutic strategies focus on the correction of phosphate, calcium, parathyroid hormone or vitamin D, a better understanding of the mechanisms of abnormal tissue calcification may lead to development of new therapeutic agents, which could reduce VC and improve cardiovascular outcome in CKD patients. The present review summarizes the following aspects: (i) the pathophysiological mechanism responsible for VC and its promoters and inhibitors, (ii) the methods for detection of VC in patients with CKD, including evaluation of arterial stiffness, and (iii) the management of VC in CKD patients.

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.

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.

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.

Chronic kidney disease-mineral and bone disorder

2018 ◽  
Author(s):  
Stuart M. Sprague ◽  
Menaka Sarav
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Osteodystrophy ◽  
Mineral Metabolism ◽  
Bone Biopsy ◽  
Fibroblast Growth Factor 23 ◽  
Critical Role ◽  
Specific Treatment ◽  
Mineral And Bone Disorder ◽  
Bone Disorder

The kidneys play a critical role in maintaining normal serum calcium and phosphorus concentrations, under the regulation of three main hormones: parathyroid hormone, calcitriol, and fibroblast growth factor 23. With the progression of chronic kidney disease (CKD), most patients develop CKD–mineral and bone disorder (CKD-MBD), which is a systemic disorder involving derangement in mineral metabolism, renal osteodystrophy, and extraskeletal calcification. Disturbances in mineral metabolism develop early in CKD and include phosphate retention, hypocalcaemia, vitamin D deficiency, and hyperparathyroidism. Renal osteodystrophy involves pathologic changes of bone morphology related to progressive CKD and is quantifiable by histomorphometry, based on bone biopsy. CKD-MBD is associated with significant morbidity, including bone loss, fractures, cardiovascular disease, immune suppression, as well as increased mortality. As the disorder begins early in the course of CKD, a proactive approach with intervention is important. Therapeutic strategies could then be employed to prevent and correct these disturbances, aiming to improve cardiovascular outcomes and survival. Current practice guidelines for CKD-MBD are based on insufficient data and high-quality studies are required before specific treatment can be advocated strongly.

scholarly journals Cardiac Remodeling in Chronic Kidney Disease

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 161 ◽  
Author(s):  
Nadine Kaesler ◽  
Anne Babler ◽  
Jürgen Floege ◽  
Rafael Kramann
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Remodeling ◽  
Mineral Metabolism ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
Current Treatment ◽  
Left Ventricular ◽  
Heart Functions

Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As kidney function declines, numerous metabolic pathways are disturbed. Kidney and heart functions are highly connected by organ crosstalk. Among others, altered volume and pressure status, ischemia, accelerated atherosclerosis and arteriosclerosis, disturbed mineral metabolism, renal anemia, activation of the renin-angiotensin system, uremic toxins, oxidative stress and upregulation of cytokines stress the sensitive interplay between different cardiac cell types. The fatal consequences are left-ventricular hypertrophy, fibrosis and capillary rarefaction, which lead to systolic and/or diastolic left-ventricular failure. Furthermore, fibrosis triggers electric instability and sudden cardiac death. This review focuses on established and potential pathophysiological cardiorenal crosstalk mechanisms that drive uremia-induced senescence and disease progression, including potential known targets and animal models that might help us to better understand the disease and to identify novel therapeutics.

scholarly journals Biological and Clinical Effects of Calciprotein Particles on Chronic Kidney Disease-Mineral and Bone Disorder

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Kenichi Akiyama ◽  
Takaaki Kimura ◽  
Kazuhiro Shiizaki
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Studies ◽  
Inflammatory Responses ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Clinical Effects ◽  
Mineral And Bone Disorder ◽  
Calciprotein Particles ◽  
Bone Disorder

Calciprotein particles (CPPs) are a new biological marker of chronic kidney disease-mineral and bone disorder (CKD-MBD). CPPs consist of phosphate, calcium, and some proteins, with phosphate being the major contributor to the level and biological activity of CPPs. Recent studies have shown the physiological and pathological significance of CPPs, including contributions to bone and mineral metabolism, and to tissue and organ impairments such as cardiovascular damage and inflammatory responses. These actions are well known as important aspects of CKD-MBD. Fibroblast growth factor 23 (FGF23), which is secreted from the bone as the phosphaturic hormone, is markedly elevated in CKD-MBD. Many clinical studies have shown significant relationships between the level of FGF23 and outcomes such as mortality, prevalence of cardiovascular disease, bone fracture, and levels of inflammatory markers. Basic and clinical studies have suggested that CPPs contribute to synthesis and secretion of FGF23. Surgical treatments such as renal transplantation and parathyroidectomy for patients with CKD-MBD suppress excess levels of phosphate, calcium, parathyroid hormone (PTH), and FGF23, which are related to the CPP level. Therefore, suppression of CPPs might also contribute to improved clinical outcomes after these treatments.

Sign in / Sign up

Export Citation Format

Share Document