Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: Cause or association?

2012 ◽  
Vol 223 (1) ◽  
pp. 86-94 ◽  
Author(s):  
William E. Moody ◽  
Nicola C. Edwards ◽  
Melanie Madhani ◽  
Colin D. Chue ◽  
Richard P. Steeds ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Early Stage

scholarly journals Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients

2022 ◽  
Author(s):  
Satyendra Kumar Sonkar ◽  
Prashant Kumar Singh ◽  
Sharad Chandra ◽  
Gyanendra Kumar Sonkar ◽  
Vivek Bhosale ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Complete Blood Count ◽  
Early Stage ◽  
Premature Mortality ◽  
Cathepsin S ◽  
Early Stages ◽  
Early Biomarker ◽  
New Biomarkers

Abstract Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p <0.05) as well as in later stages of CKD (p <0.05). CVD was also more common in patients in early stage CKD. In early stages CKD, Cat S and CVD were positively correlated. Conclusion: These findings suggest that serum Cat S might be useful as an early biomarker for CVD in CKD patients.

scholarly journals Most exposed: the endothelium in chronic kidney disease

2019 ◽  
Vol 35 (9) ◽  
pp. 1478-1487 ◽  
Author(s):  
Marc Vila Cuenca ◽  
Peter L Hordijk ◽  
Marc G Vervloet
Keyword(s):  
Risk Factors ◽  
Reactive Oxygen Species ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Oxygen Species ◽  
Pathological Changes ◽  
Endothelial Lining ◽  
Traditional Risk Factors

Abstract Accumulating evidence indicates that the pathological changes of the endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Non-traditional risk factors related to CKD are associated with the incidence of cardiovascular disease, but their role in uraemic endothelial dysfunction has often been disregarded. In this context, soluble α-Klotho and vitamin D are of importance to maintain endothelial integrity, but their concentrations decline in CKD, thereby contributing to the dysfunction of the endothelial lining. These hormonal disturbances are accompanied by an increment of circulating fibroblast growth factor-23 and phosphate, both exacerbating endothelial toxicities. Furthermore, impaired renal function leads to an increment of inflammatory mediators, reactive oxygen species and uraemic toxins that further aggravate the endothelial abnormalities and in turn also inhibit the regeneration of disrupted endothelial lining. Here, we highlight the distinct endothelial alterations mediated by the abovementioned non-traditional risk factors as demonstrated in experimental studies and connect these to pathological changes in CKD patients, which are driven by endothelial disturbances, other than atherosclerosis. In addition, we describe therapeutic strategies that may promote restoration of endothelial abnormalities by modulating imbalanced mineral homoeostasis and attenuate the impact of uraemic retention molecules, inflammatory mediators and reactive oxygen species. A clinical perspective on endothelial dysfunction in CKD may translate into reduced structural and functional abnormalities of the vessel wall in CKD, and ultimately improved cardiovascular disease.

P3493Uremic toxin induced endothelial dysfunction can be restored by inhibition of the aryl hydrocarbon receptor: implications for cardiovascular disease treatment in chronic kidney disease patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kompa ◽  
C Nguyen ◽  
A J Edgley ◽  
D J Kelly
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Aryl Hydrocarbon Receptor ◽  
Uremic Toxin ◽  
Aryl Hydrocarbon ◽  
Endothelium Dependent Relaxation

Abstract Introduction Cardiovascular disease (CVD) mortality is significantly higher in chronic kidney disease (CKD) patients, with vascular calcification and atherosclerosis proving to be major contributors. Endothelial dysfunction is an early marker of atherosclerosis, triggered by oxidative stress and reduced nitric oxide production. The uremic toxin indoxyl sulphate (IS), a protein-bound non-dialyzable molecule derived from dietary tryptophan that accumulates in the blood of CKD patients, activates the aryl hydrocarbon receptor (AhR) promoting downstream cytochrome P450 1A1 (CYP1A1) expression mediating oxidative stress and potentially endothelial dysfunction. Targeting IS-induced AhR activation in the endothelium has not previously been examined and may represent a novel approach in targeting endothelial dysfunction. Purpose To assess the ability of the AhR antagonist, CH223191, to inhibit IS-mediated impairment of endothelial function and disruption of redox balance. Methods To assess endothelium-dependent relaxation, the thoracic aorta from adult male Sprague Dawley rats (N=10) were used in ex vivo experiments. Rings (5mm) from the aorta were exposed to IS (300μM) in the presence and absence of the AhR antagonist CH223191 (1 and 10μM), prior to pre-constriction of the vessel with phenylephrine (30μM) followed by relaxation with acetylcholine (ACh; 1nM-30μM). Control rings were not exposed to IS or CH223191 to determine normal endothelial responses to ACh. Responses were recorded with isometric force transducers connected to a PowerLab using Chart Software. Tissue sections from these rings were stained for superoxide using dihydroethidium. To examine key AhR-mediated oxidative stress pathways, separate aortic rings were exposed to IS and CH223191, under the above conditions, for 4 hours prior to RNA extraction and real-time PCR analysis. Results IS reduced the maximum level of endothelium-dependent relaxation (Rmax) to 50.17±2.71% (P<0.001) compared to control (86.00±3.93%). In the presence of IS, CH223191 restored Rmax to 77.74±3.14% (1μM) and 81.63±3.27% (10μM) (Figure, P<0.001). The potency of ACh, known as the pEC50 (negative logarithm of the effective concentration of ACh to produce a relaxation response of 50%), in control tissues (−7.08±0.07) was increased 100-fold following exposure of IS (−5.10±0.13; P<0.001). CH223191 restored pEC50 back to control values (1μM, −6.62±0.09; 10μM, −6.83±0.08; P<0.05). IS-exposed rings increased superoxide expression (P<0.001) and CYP1A1 gene expression (P<0.001), CH223191 restored expression of both superoxide (P<0.001) and CYP1A1 (P<0.001) back to control levels. CH223191 restores endothelial function Conclusion Our findings demonstrate the adverse impact of IS-mediated AhR activation on the vascular endothelium, where oxidative stress may play a critical role inducing endothelial dysfunction in the vasculature of the heart and kidneys. AhR inhibition may provide a novel therapy for CVD in the CKD setting. Acknowledgement/Funding National Health and Medical Research Council of Australia Program Grant

scholarly journals The Impact of Insulin Resistance and Chronic Kidney Disease on Inflammation and Cardiovascular Disease

2018 ◽  
Vol 11 ◽  
pp. 117955141879225 ◽  
Author(s):  
Constantine E Kosmas ◽  
Delia Silverio ◽  
Christiana Tsomidou ◽  
Maria D Salcedo ◽  
Peter D Montan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Early Stage ◽  
Scientific Data ◽  
Low Grade ◽  
The Impact ◽  
Low Grade Inflammation

There is extensive evidence showing that insulin resistance (IR) is associated with chronic low-grade inflammation. Furthermore, IR has been shown to increase the risk for cardiovascular disease (CVD), even in nondiabetic patients, and is currently considered as a “nontraditional” risk factor contributing to CVD by promoting hypertension, oxidative stress, endothelial dysfunction, dyslipidemia, and type 2 diabetes mellitus. However, chronic kidney disease (CKD) is also considered a state of low-grade inflammation. In addition, CKD is considered an IR state and has been described as an independent risk factor for the development of CVD, as even early-stage CKD is associated with an estimated 40% to 100% increase in CVD risk. There is also strong evidence indicating that inflammation per se plays a crucial role in both the initiation and progression of CVD. Given the above, the combined effect of IR and CKD may significantly increase the risk of inflammation and CVD. This review aims to focus on the complex interplay between IR, CKD, inflammation, and CVD and will present and discuss the current clinical and scientific data pertaining to the impact of IR and CKD on inflammation and CVD.

Abstract 5930: The Effect of Spironolactone on Myocardial Structure and Function Measured by Echocardiography in Patients with Early Stage Chronic Kidney Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Nicola C Edwards ◽  
Richard P Steeds ◽  
Charles J Ferro ◽  
John N Townend
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ace Inhibitors ◽  
Early Stage ◽  
Structure And Function ◽  
Lv Function ◽  
Lv Mass ◽  
Myocardial Structure ◽  
And Function

Introduction Early stage chronic kidney disease (CKD) is associated both with a high rate of adverse cardiovascular events and abnormal myocardial structure and function. Activation of the renin-angiotensin-aldosterone system is common in CKD and may result in adverse inflammatory, fibrotic and hypertrophic effects upon the heart and vasculature. Treatment with ACE inhibitors and ARBs frequently fails to suppress aldosterone production. We hypothesized that addition of the aldosterone antagonist spironolactone to ACE Inhibitors and ARB’s might reduce left ventricular (LV) mass and improve systolic and diastolic function measured by echocardiography. Methods One hundred and seventeen patients with stage 2 and 3 CKD, controlled hypertension (<130/85mmHg) and no history of cardiovascular disease or diabetes were recruited in to a double blind placebo controlled trial. After an active 4 week run in of spironolactone 25mg daily, patients were randomized to continue this treatment or receive placebo for a further 36 weeks. Echocardiographic assessment of LV mass, systolic and diastolic LV function was performed before run in and after 40 weeks of treatment. Results Compared to placebo, spironolactone reduced LV mass (mean (SD) −10g ± 10 vs.+3g ± 13, p<0.01). There was an improvement in LV Tei Index (−0.08 ± 0.1 vs. −0.001 ± 0.1, p<0.01) and mean basal long axis annular systolic velocities (Sm +1.4cm/s ± 1.9 vs. +0.1cm/s ± 1.1, p<0.01) but no difference in ejection fraction (+3% ± 5 vs.+2% ± 7). Transmitral E/A filing ratio (E/A +0.3 ± 0.3 vs −0.02 ± 0.2, p<0.05), basal annular early myocardial diastolic velocities (Ea +0.5cm/s ± 2.1 vs. −0.3cm/s ± 2.1, p<0.05), E/Ea ratio (−0.7 ± 1.9 vs. 0.1 ± 2.0, p<0.05), and colour flow propogation velocities (+8.7 ± 16.3 vs. −0.1 ± 16.6, p<0.05) were all improved. Systolic blood pressure was reduced with spironolactone but was not an independent predictor of change in any echocardiographic parameters. Conclusion Treatment with spironolactone reduced LV mass and improved both systolic and diastolic LV function. These data suggest that aldosterone plays an important role in cardiovascular disease in CKD and provides support for a clinical outcome trial investigating the use of aldosterone inhibitors to reduce cardiovascular risk.

scholarly journals Impact of Continuous Erythropoietin Receptor Activator on Selected Biomarkers of Cardiovascular Disease and Left Ventricle Structure and Function in Chronic Kidney Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9
Author(s):  
Piotr Bartnicki ◽  
Jacek Rysz ◽  
Beata Franczyk ◽  
Zbigniew Baj ◽  
Ewa Majewska
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Left Ventricle ◽  
Structure And Function ◽  
Erythropoietin Receptor ◽  
Receptor Activator ◽  
Continuous Erythropoietin Receptor Activator ◽  
And Function

Background. Cardiovascular morbidity and mortality are very high in patients with chronic kidney disease (CKD). The purpose of this study is to evaluate the impact of continuous erythropoietin receptor activator (CERA) on selected biomarkers of cardiovascular disease, left ventricle structure, and function in CKD.Material and Methods. Peripheral blood was collected from 25 CKD patients before and after CERA treatment and 20 healthy subjects. In serum samples, we assessed inflammatory markers (IL-1β, TNF-RI, TNF-RII, sFas, sFasL, MMP-9, TIMP-1, and TGF-β1), endothelial dysfunction markers (sE-selectin, sICAM-1, and sVCAM-1), and volume-related marker (NT-proBNP). All subjects underwent echocardiography and were evaluated for selected biochemical parameters (Hb, creatinine, and CRP).Results. Evaluated biomarkers and echocardiographic parameters of left ventricle structure were significantly increased but left ventricle EF was significantly decreased in CKD patients compared to controls. After CERA treatment, we observed a significant increase of Hb and left ventricle EF and a significant decrease of NT-proBNP and MMP-9. There was a significant negative correlation between Hb and TNF-RI, sICAM-1, and IL-1β.Conclusions. Our results indicate that selected biomarkers related to cardiovascular risk are significantly increased in CKD patients compared to controls. CERA treatment has anti-inflammatory action, diminishes endothelial dysfunction, and improves left ventricle function in these patients.

ASSESSMENT OF KIDNEY FUNCTIONAL RESERVE ON THE BACKGROUND OF ANTI-AGGREGATE THERAPY IN CHRONIC KIDNEY DISEASE II-III STAGE

2020 ◽  
Vol 6 (1) ◽  
pp. 49-54
Author(s):  
Khabib Barnoev ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Comparative Study ◽  
Early Stage ◽  
Raw Material ◽  
Functional Reserve ◽  
Functional Reserves ◽  
Term Administration ◽  
Antiaggregant Therapy

The article presents the results of a study to assess the functional reserve of the kidneys against the background of a comparative study of antiaggregant therapy dipyridamole and allthrombosepin in 50 patients with a relatively early stage of chronic kidney disease. Studies have shown that long-term administration of allthrombosepin to patients has resulted in better maintenance of kidney functional reserves. Therefore, our research has once again confirmed that diphtheridamol, which is widely used as an antiaggregant drug in chronic kidney disease, does not lag behind the domestic raw material allthrombosepin

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