scholarly journals Association between PCSK9 Levels and Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction in a Population of Nondialysis Chronic Kidney Disease Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Evangelia Dounousi ◽  
Constantinos Tellis ◽  
Paraskevi Pavlakou ◽  
Anila Duni ◽  
Vasillios Liakopoulos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Lipid Metabolism ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Endothelial Damage ◽  
Apo B ◽  
Markers Of Inflammation ◽  
Cardiovascular Morbidity And Mortality

Proprotein convertase subtilisin/kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress, and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress, and endothelial damage in patients with CKD. Patients and Methods. Ninety-two patients with CKD stages II-ΙV (eGFR CKD-EPI 47.3 ± 25.7  ml/min/1.73 m2, mean age 66 years, 51 men) were included in the study. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension, diabetes mellitus, and history of cardiovascular disease), renal function indices (eGFR, proteinuria–UPR/24 h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), APO-A1, and APO-B), and soluble biomarkers of inflammation, oxidative stress, and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, and sVCAM-1). Results. The mean plasma value of PCSK9 was 278.1 ng/ml. PCSK9 levels showed direct correlation with serum triglycerides ( p = 0.03 ), Lp(a) ( p = 0.01 ), and sICAM-1 levels ( p = 0.03 ). There was no significant correlation between PCSK9 levels and indices of the renal function, other lipid profile parameters, inflammatory markers, or comorbidities. Multiple regression analysis showed a significant effect of Lp(a) on PCSK9 levels, and for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935-5.228, p = 0.006 ). At the same time, patients receiving statins are expected to have on average 63.8 ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6-113.5, p = 0.012 ). Conclusion. Plasma levels of PCSK9 in nondialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD.

scholarly journals MO474PCSK9 LEVELS AND MARKERS OF INFLAMMATION, OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION IN A POPULATION OF NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS: IS THERE AN ASSOCIATION?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Evangelia Ntounousi ◽  
Konstantinos Tellis ◽  
Paraskevi Pavlakou ◽  
Anila Duni ◽  
Vassilios Liakopoulos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Lipid Metabolism ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Endothelial Damage ◽  
Apo B ◽  
Markers Of Inflammation ◽  
Ckd Stage

Abstract Background and Aims Proprotein convertase subtilisin / kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress and endothelial damage in patients with CKD. Method Ninety-two patients with CKD stage II-ΙV (eGRF CKD-EPI 47.3 ±25.7ml/min/1,73m2, mean age 66 years, 51 men) were included. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension; diabetes mellitus, history of cardiovascular disease), renal function indices (eGFR, proteinuria – UPR/24h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp (a), APO-A1, APO-B), as well as soluble biomarkers of inflammation, oxidative stress and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, sVCAM-1). Results The mean plasma value of PCSK9 was 278.1ng/ml. PCSK9 levels showed direct correlation with serum triglycerides (p = 0.03), Lp(a) (p = 0.01), and sICAM-1 levels (p = 0.03). There was no significant correlation between PCSK9 levels and indices of renal function, other lipid profile parameters, inflammatory markers or co-morbidities. Multiple regression analysis showed a significant effect of the Lp(a) on PCSK9 levels, for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935 - 5.228, p=0.006). At the same time, patients receiving statins are expected to have on average 63.8ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6 - 113.5 p=0.012). Conclusion Plasma levels of PCSK9 in non-dialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD

scholarly journals Finerenone Attenuates Endothelial Dysfunction and Albuminuria in a Chronic Kidney Disease Model by a Reduction in Oxidative Stress

2018 ◽  
Vol 9 ◽  
Author(s):  
Raquel González-Blázquez ◽  
Beatriz Somoza ◽  
Marta Gil-Ortega ◽  
Miriam Martín Ramos ◽  
David Ramiro-Cortijo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Disease Model

scholarly journals Impact of Intravenous Iron on Oxidative Stress and Mitochondrial Function in Experimental Chronic Kidney Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 498 ◽  
Author(s):  
Faisal Nuhu ◽  
Anne-Marie Seymour ◽  
Sunil Bhandari
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Iron Deficiency ◽  
Glutathione Peroxidase ◽  
Mitochondrial Function ◽  
Iron Deficiency Anaemia ◽  
Deficiency Anaemia ◽  
Iv Iron

Background: Mitochondrial dysfunction is observed in chronic kidney disease (CKD). Iron deficiency anaemia (IDA), a common complication in CKD, is associated with poor clinical outcomes affecting mitochondrial function and exacerbating oxidative stress. Intravenous (iv) iron, that is used to treat anaemia, may lead to acute systemic oxidative stress. This study evaluated the impact of iv iron on mitochondrial function and oxidative stress. Methods: Uraemia was induced surgically in male Sprague-Dawley rats and studies were carried out 12 weeks later in two groups sham operated and uraemic (5/6 nephrectomy) rats not exposed to i.v. iron versus sham operated and uraemic rats with iv iron. Results: Induction of uraemia resulted in reduced iron availability (serum iron: 31.1 ± 1.8 versus 46.4 ± 1.4 µM), low total iron binding capacity (26.4 ± 0.7 versus 29.5 ± 0.8 µM), anaemia (haematocrit: 42.5 ± 3.0 versus 55.0 ± 3.0%), cardiac hypertrophy, reduced systemic glutathione peroxidase activity (1.12 ± 0.11 versus 1.48 ± 0.12 U/mL), tissue oxidative stress (oxidised glutathione: 0.50 ± 0.03 versus 0.36 ± 0.04 nmol/mg of tissue), renal mitochondrial dysfunction (proton/electron leak: 61.8 ± 8.0 versus 22.7 ± 5.77) and complex I respiration (134.6 ± 31.4 versus 267.6 ± 26.4 pmol/min/µg). Iron therapy had no effect on renal function and cardiac hypertrophy but improved anaemia and systemic glutathione peroxidase (GPx) activity. There was increased renal iron content and complex II and complex IV dysfunction. Conclusion: Iron therapy improved iron deficiency anaemia in CKD without significant impact on renal function or oxidant status.

scholarly journals Oxidative Balance and Inflammation in Hemodialysis Patients: Biomarkers of Cardiovascular Risk?

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Daniele La Russa ◽  
Daniela Pellegrino ◽  
Alberto Montesanto ◽  
Paolo Gigliotti ◽  
Anna Perri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Cardiovascular Complications ◽  
Hemodialysis Patients ◽  
Healthy Population ◽  
Oxidative Balance

During chronic kidney disease, the progressive deterioration of renal function induces several biological/clinical dysfunctions, including enhancement of synthesis of inflammation/oxidative stress mediators. Impaired renal function is an independent cardiovascular risk factor; indeed, cardiovascular complications dominate the landscape of both chronic kidney disease and end-stage renal disease. The aim of this study is to explore the correlation between the global oxidative balance in hemodialysis patients and both inflammatory markers and cardiovascular events. Using photometric tests, this study explored plasmatic oxidative balance in 97 hemodialysis patients compared to a healthy population. In the hemodialysis patients, we showed that oxidative stress values were significantly lower than in controls while effectiveness in the antioxidant barrier was significantly increased in the hemodialysis group. Furthermore, we highlighted a strong correlation between oxidative index and blood levels of C-reactive protein. When patients were divided into two groups based on previous cardiovascular events, we found that subjects with previous cardiovascular events had higher values of both oxidative stress and antioxidant barrier than patients without cardiovascular events. Our results indicated that in hemodialysis patients, the clinical and prognostic significance of oxidative status is very different from general population. As cardiovascular complications represent a strong negative factor for survival of hemodialysis patients, the research of new cardiovascular risk biomarkers in these patients takes on particular importance in order to translate them into clinical practice/primary care.

Endothelial damage and vascular calcification in patients with chronic kidney disease

2014 ◽  
Vol 307 (11) ◽  
pp. F1302-F1311 ◽  
Author(s):  
Sagrario Soriano ◽  
Andrés Carmona ◽  
Francisco Triviño ◽  
Mariano Rodriguez ◽  
Marina Alvarez-Benito ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vascular Smooth Muscle Cells ◽  
Endothelial Damage ◽  
Endothelial Microparticles ◽  
Healthy Donors ◽  
Cardiovascular Morbidity And Mortality

Vascular calcification (VC) is a frequent complication of chronic kidney disease (CKD) and is a predictor of cardiovascular morbidity and mortality. In the present study, we investigated the potential involvement of endothelial microparticles (MPs) and endothelial progenitor cells (EPCs) in the generation of VC in CKD patients. The number of circulating EMPs is greater in patients with VC than without VC (307 ± 167 vs. 99 ± 75 EMPs/μl, P < 0.001). The percentage of EPCs is significantly lower in patient with VC than in patients without VC (0.14 ± 0.11% vs. 0.25 ± 0.18%, P = 0.002). The number of EPCs expressing osteocalcin (OCN) was higher in VC patients (349 ± 63 cells/100,000) than in non-VC patients (139 ± 75 cells/100,000, P < 0.01). In vitro, MPs obtained from CKD patients were able to induce OCN expression in EPCs from healthy donors; the increase in OCN expression was more accentuated if MPs were obtained from CKD patients with VC. MPs from CKD patients also induced OCN expression in vascular smooth muscle cells and fibroblasts. In CKD patients, the rise in endothelial MPs associated with a decrease in the number of EPCs, suggesting an imbalance in the processes of endothelial damage and repair in CKD patients, mainly those with VC. Our results suggest that EPCs, through OCN expression, may directly participate in the process of VC.

scholarly journals Thrombomodulin as a New Marker of Endothelial Dysfunction in Chronic Kidney Disease in Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Dorota Drożdż ◽  
Monika Łątka ◽  
Tomasz Drożdż ◽  
Krystyna Sztefko ◽  
Przemko Kwinta
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Cystatin C ◽  
Oxidized Ldl ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Oxidative Stress Biomarkers ◽  
Ckd Stage

Endothelial dysfunction (ED) and oxidative stress are potential new pathomechanisms of cardiovascular diseases in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between endothelial dysfunction, oxidative stress biomarkers, and cardiovascular risk factors in children with CKD. Serum oxidized LDL (oxLDL), protein carbonyl group, urea, creatinine, cystatin C, thrombomodulin, asymmetric dimethylarginine (ADMA), von Willebrand factor, brain natriuretic peptide (BNP), lipids, high sensitivity C-reactive protein, intercellular adhesion molecule-1 levels, and albuminuria were measured. Anthropometric, ambulatory blood pressure (BP) measurements and echocardiography were performed. The studied group consisted of 59 patients aged 0.7–18.6 (mean 11.1) years with stages 1 to 5 CKD. Thrombomodulin strongly correlated with creatinine (R=0.666; p<0.001), cystatin C (R=0.738; p<0.001), BNP (R=0.406; p=0.001), ADMA (R=0.353; p=0.01), oxLDL (R=0.340; p=0.009), 24-hour systolic (R=0.345; p=0.011) and mean (R=0.315; p<0.05) BP values, and left ventricular mass index (LVMI, R=0.293; p=0.024) and negatively with estimated glomerular filtration rate (R=−0.716; p<0.001). In children with CKD, TM strongly depended on kidney function parameters, oxLDL levels, and 24-hour systolic and mean BP values. Thrombomodulin seems to be a valuable marker of ED in CKD patients, correlating with CKD stage as well as oxidative stress, BP values, and LVMI.

scholarly journals Lipid spectrum and function of kidneys before and after liver transplantation

Kardiologiia ◽  
2019 ◽  
Vol 59 (6S) ◽  
pp. 17-23
Author(s):  
E. D. Kosmacheva ◽  
A. E. Babich
Keyword(s):  
Chronic Kidney Disease ◽  
Liver Transplantation ◽  
Renal Function ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Total Cholesterol ◽  
Renal Dysfunction ◽  
Inverse Correlation ◽  
Study Results ◽  
Lipid Spectrum

Background. In patients after liver transplantation cardiovascular complications is the third main reason of death afer allograf failure and infections. The most important factors in the development of cardiovascular diseases are dyslipidemia and impaired renal function. The aim of the study was to investigate the lipid spectrum and renal function in liver recipients in real clinical practice and the correspondence of their correction to current clinical recommendations for the diagnosis and treatment of dyslipidemia and chronic kidney disease (CKD). Methods. A retrospective analysis of lipid spectrum and renal function in patients who underwent OLT in Research Institute – Regional Clinical Hospital №1, Krasnodar was performed. The level of creatinine, GFR and lipid spectrum was studied before and 36 months after liver transplantation. The GFR was calculated using the formula CKD‑EPI (Chronic Kidney Disease Epidemiology Collaboration). Statistical analysis of the study results was made using the program Statistica 10. Results. Liver recipients have a significantly higher total cholesterol by 31.0% (p<0.01) in comparison with the baseline before surgery. Total cholesterol was increased in 13.7% (p<0.01), triglycerides in 12.3% (p<0.01) before transplantation. Tree years after transplantation, the increasion in cholesterol was registered in 42.6% (p<0.01) and triglycerides in 37.9% (p <0.01), respectively. 3 years after transplantation reduction of GFR was observed in comparison with the baseline by 22.6% (p=0.00006). Verification of chronic kidney disease and statin administration in patients were carried out in some cases. The levels of total cholesterol and triglycerides had a reliable inverse correlation with GFR (r = ‑0.42; p<0.01 and r = ‑0.36; p<0.05). Conclusions. In the long‑term postoperative period there was an impaired lipid metabolism and decreased level of GFR. Dyslipidemia was closely related to the progression of renal dysfunction in liver recipients, an inverse correlation was established between the glomerular filtration rate and the increasion in cholesterol and triglyceride levels. It is necessary to increase the attention of physicians with regard to timely correction of lipid metabolism disorders and detection of initial manifestations of renal dysfunction.

scholarly journals EVALUATION OF INFLAMMATION AND ENDOTHELIAL DYSFUNCTION BIOMARKERS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS IN SOKOTO, NIGERIA

2021 ◽  
Vol 1 (1) ◽  
pp. 1-9
Author(s):  
C. A. Otitolaiye ◽  
D. M. Sahabi ◽  
A. M. Makusidi ◽  
Y. Saidu ◽  
L. S. Bilbis
Keyword(s):  
Chronic Kidney Disease ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Progressive Increase ◽  
Necrosis Factor Alpha ◽  
Reactive Protein ◽  
Cardiovascular Morbidity And Mortality ◽  
Tnf Α ◽  
Variable Equation

Inflammation and endothelial dysfunction have been known to be involved in the pathogenesis of cardiovascular diseases. As such, examining the levels of inflammation and endothelial dysfunction is very critical to the prevention of cardiovascular diseases among chronic kidney disease (CKD) patients. This study aimed to investigate the progression of inflammation and endothelial dysfunction among CKD patients in Sokoto. A total of 67 CKD patients were divided into 5 groups based on the stages of their kidney disease calculated using the MDRD 4-variable equation for estimated glomerular filtration rate (eGFR). The presence of inflammation was determined by C-Reactive Protein (CRP) and Tumor Necrosis Factor alpha, while endothelial dysfunction was determined by the levels of Asymmetric dimethylarginine (ADMA) using ELISA kits. The mean eGFR of the patients was 49.97 ± 4.69 ml/min/1.73m2. There was significant increase (p<0.05) in CRP, TNF-α and ADMA of the CKD patients across the stages as compared to the non-CKD subjects. It was observed that as the CRP, TNF-α and ADMA increase, the eGFR significantly (p<0.05) decreases. Both CRP and TNF-α indicated a significantly positive correlation (p<0.05) with ADMA. The results indicated progressive increase in inflammation and endothelial dysfunction as CKD deteriorates. In addition, increased levels of inflammation could directly affect endothelial dysfunction, thereby aggravating cardiovascular morbidity and mortality among CKD patients in Sokoto. Otitolaiye, C. A. | Department of Biochemistry, Sokoto State University, Sokoto, Nigeria

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