scholarly journals Impact of Homoarginine on Myocardial Function and Remodeling in a Rat Model of Chronic Renal Failure

2022 ◽  
Vol 27 ◽  
pp. 107424842110546
Author(s):  
Vitali Koch ◽  
Christophe Weber ◽  
Johannes H. Riffel ◽  
Kristina Buchner ◽  
Sebastian J. Buss ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Myocardial Fibrosis ◽  
Cardiac Remodeling ◽  
Heart Function ◽  
Plasma Concentrations ◽  
Left Ventricular ◽  
Cross Sectional

Purpose: Low plasma concentrations of the amino acid homoarginine (HA) have been shown to correlate with adverse cardiovascular outcome, particularly in patients with chronic kidney disease. The present study sought to investigate the effect of HA treatment on cardiac remodeling in rats undergoing artificially induced renal insufficiency by 5/6 nephrectomy (5/6 Nx). Methods: A total of 33 male Wistar rats were randomly divided into sham and 5/6 Nx groups, receiving either placebo treatment or 400 mg·kg−1·day−1 HA over a 4-week period. Results: 5/6 Nx per se resulted in adverse myocardial remodeling with aggravated cardiac function and associated cardiac overload as the most obvious alteration (−23% ejection fraction, P < 0.0001), as well as increased myocardial fibrosis (+80%, P = 0.0005) compared to placebo treated sham animals. HA treatment of 5/6 Nx rats has led to an improvement of ejection fraction (+24%, P = 0.0003) and fractional shortening (+21%, P = 0.0126), as well as a decrease of collagen deposition (−32%, P = 0.0041), left ventricular weight (−14%, P = 0.0468), and myocyte cross-sectional area (−12%, P < 0.0001). These changes were accompanied by a downregulation of atrial natriuretic factor (−65% P < 0.0001) and collagen type V alpha 1 chain (−44%, P = 0.0006). Sham animals revealed no significant changes in cardiac function, myocardial fibrosis, or any of the aforementioned molecular changes after drug treatment. Conclusion: Dietary HA supplementation appears to have the potential of preventing cardiac remodeling and improving heart function in the setting of chronic kidney disease. Our findings shed new light on HA as a possible new therapeutic agent for patients at high cardiovascular risk.

scholarly journals The Copenhagen chronic kidney disease echo study (COInCYDE)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Landler ◽  
S Bro ◽  
B Feldt-Rasmussen ◽  
D Hansen ◽  
A.L Kamper ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Funding Source ◽  
Ckd Stage ◽  
Significant Difference ◽  
Stage 1

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark

scholarly journals Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease

Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 520 ◽  
Author(s):  
Shanmugakumar Chinnappa ◽  
Yu-Kang Tu ◽  
Yi Chun Yeh ◽  
Griet Glorieux ◽  
Raymond Vanholder ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Dysfunction ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Cross Sectional Study ◽  
Left Ventricular ◽  
Uremic Toxins ◽  
Cross Sectional ◽  
The Individual

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2–5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.

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 A tertiary care centre profile of heart diseases among diagnosed cases of chronic kidney disease

2020 ◽  
Vol 8 (2) ◽  
pp. 652
Author(s):  
Vijay Bakhtar ◽  
Niyati Bakhtar ◽  
Neha Pandey ◽  
Nikhil Bakhtar
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Heart Diseases ◽  
Tertiary Care ◽  
Cross Sectional Study ◽  
Left Ventricular ◽  
Tertiary Care Centre ◽  
Cross Sectional ◽  
Cardiac Evaluation

Background: Chronic Kidney Disease (CKD) is a risk factor for development of cardiovascular diseases. Cardiovascular diseases are the predominant cause of morbidity and mortality in patients with CKD. There is limited data on cardiovascular diseases among CKD patients from developing countries including India. With the present study, the prevalence and patterns of cardiac diseases among patients with CKD were profiled.Methods: This was a cross sectional study in which 217 patients with CKD were studied over a period of two years and six months. Data on demographic characteristics and risk factors for cardiovascular diseases were collected using a standardized questionnaire. Cardiac evaluation was done using resting ECG and echocardiography.Results: One hundred eighteen (54.4%) patients had either eccentric or concentric LVH. Patients with LVH were more likely to be hypertensive (p<0.001) or anemic (p=0.034). Up to 9.2% of study subjects had valvular heart disease (rheumatic or degenerative) and 22% had pericarditis. Patients with pericarditis were more likely to have a serum urea concentration greater than 60mg/dl (p=0.327). Forty-one patients (18.9%) had left ventricular systolic failure (EF<50%). There was a statistically insignificant higher prevalence of systolic failure in patients with LVH (21% vs. 16%), (p=0.346). Thirty-eight participants (17.5%) had diastolic failure while 2% had cardiac rhythm abnormalities.Conclusions: Cardiac abnormalities are common in a relatively young Indian population with CKD. Clinicians should routinely screen and manage cardiovascular disease in CKD patients.

scholarly journals Serum levels of matrix metalloproteinases MMP-2, MMP-3, MMP-9 and tissue inhibitor of matrix metalloproteinase TIMP-2 in patients with myocarditis.

2021 ◽  
Author(s):  
Małgorzata Kobusiak-Prokopowicz ◽  
Konrad Kaaz ◽  
Dominik Marciniak ◽  
Bożena Karolko ◽  
Andrzej Mysiak
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Matrix Metalloproteinases ◽  
Ejection Fraction ◽  
Myocardial Damage ◽  
Serum Levels ◽  
Left Ventricular ◽  
Kidney Damage ◽  
Left Ventricular Ejection ◽  
Longitudinal Deformation

Abstract Background: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, certain stimuli cause the upregulation of MMPs, which can lead to pathological remodeling of the ECM. We assessed serum levels of MMPs and TIMP-2 in patients with myocarditis and their relationship(s) to myocardial damage.Methods: In total, 45 patients with myocarditis who underwent cardiac magnetic resonance imaging were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. Results: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with ejection fraction values in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p<0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (p<0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage.Conclusions:1. We demonstrated serum MMP-2, MMP-3, and TIMP-2 concentrations were related to left ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium.2. The occurrence of other heart diseases was an important element in modifying the relationship between MMPs and the degree of myocardial damage.3. Chronic kidney damage in patients with myocarditis results in increased MMP activity. A negative correlation between eGFR and MMP-2, MMP-3 and TIMP-2, and a positive correlation between creatinine and MMP-3 levels, underlines the role of fibrosis in myocarditis with concomitant chronic kidney disease.

scholarly journals The risks and benefits of spironolactone use in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Obertynska
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Left Ventricular Ejection Fraction ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Public Institution ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Purpose Mineralocorticoid receptor antagonists (MRAs) remain underused in cases of heart failure with a reduced left ventricular ejection fraction (HFrEF) and chronic kidney disease (CKD), largely due to the fear of inducing worsening of renal function (RF) and hyperkalemia (HK), particularly in combination with renin angiotensin inhibitors. The aim was to investigate the safety use of spironolactone (SP) in patients with HFrEF (ejection fraction &lt;40%) and CKD and determine predictors of worsening of RF and developing HK. Methods 208 patients with HFrEF (on top of standard therapy including ACE-I or an ARB) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K) and creatinine (C) levels, plasma aldosterone (AS) and NT-proBNP were estimated at baseline and at week 12. After biochemical evaluation, 101 patients started on SP treatment with a median dose of 23 mg daily (titrated). K and RF were checked at weeks 1, 2, 4, 6, 8, 12. Results K and C levels increased significantly after start of SP: mean K levels increased from 4.47±0.59 to 5.23±0.57 mEq/l, (P&lt;0.01) and was dose dependent. After 12 weeks of treatment the incidence of severe HK (K+ ≥6.0 mmol/L) was &lt;5%, K 5.5–5.9 mmol/L occurred in 13 patients (13%) and it was predicted by baseline eGFR≤35 ml/min/1.73 m2. and K ≥5.0 mmol/L/. Subsequently, these patients required a prescription of K binders. Mean eGFR on SP decreased from 48.34±2.23 to 42.19±2.65 ml/min/1.73 m2 (P&lt;0.01) and a significant decrease in GFR was observed only during the first month (P &lt;0.01) with not significant increasing to 6 and 12 weeks after the start of SP. Five patients (5%) on SP experienced significant decline of RF result in withdrew SP. Age, NT-proBNP concentration &gt;1550 ng/L and eGFR ≤35 ml/min/1.73 m2 at baseline had modest discriminative powers for predicting decline of RF (0.456, P&lt;0.01; 0.542, P&lt;0.001; 0.712, P&lt;0.001; respectively). At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.298, p&lt;0.001). The SP treatment resulted in significantly reduced NT-proBNP and AS (P&lt;0.01; P&lt;0.05 respectively). By linear regression analysis in SP group the eGFR was associated with NT-proBNP change (0.362, P&lt;0.05). Conclusion In patient with HFrEF and CKD the risk-benefit ratio of spironolactone with respect to renal failure appears favourable due to improvement of the neurohumoral profile. Although the renal disfunction and hyperkalemia on spironolactone are common: approximately 18% patients required the prescription of K binders and 5% required the withdrew SP duo to decline RF, the occurrence of hyperkalemia was predicted by baseline potassium level and eGFR. Age, higher level of NT-proBNP and eGFR were identified as potential predictors of worsening of RF. So, caution should be advised when using spironolactone in HFrEF with CKD and potassium of ≥5.0 mmol/L and eGFR ≤35 ml/min/1.73 m2 and NT-proBNP concentration &gt;1550 ng/L for safety reasons. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Medical University

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