scholarly journals Finerenone Reduces Intrinsic Arterial Stiffness in Munich Wistar Frömter Rats, a Genetic Model of Chronic Kidney Disease

2020 ◽  
Vol 51 (4) ◽  
pp. 294-303 ◽  
Author(s):  
Marta Gil-Ortega ◽  
Elena Vega-Martín ◽  
Miriam Martín-Ramos ◽  
Raquel González-Blázquez ◽  
Helena Pulido-Olmo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Superoxide Anion ◽  
Genetic Model ◽  
Mesenteric Arteries ◽  
Mineralocorticoid Receptor Antagonist ◽  
No Bioavailability

Background: Development of albuminuria and arterial stiffness in Munich Wistar Frömter (MWF) rats, a model of chronic kidney disease, is related to alterations in extracellular matrix, increased oxidative stress, and endothelial dysfunction. Finerenone (FIN), a novel, nonsteroidal, potent, and selective mineralocorticoid receptor antagonist, improves endothelial dysfunction through enhancing nitric oxide (NO) bioavailability and decreasing superoxide anion levels due to an upregulation in vascular and renal superoxide dismutase activity. We hypothesize that FIN reduces arterial stiffness in this model associated to the reduction in albuminuria and matrix metalloproteinase (MMP)-2/9 activity. Methods: Twelve-week-old MWF rats with established albuminuria and age-matched normoalbuminuric Wistar (W) rats were treated with FIN (10 mg/kg/day, once-daily oral gavage) or with vehicle (control, C) for 4 weeks. Results: Arterial stiffness was significantly higher in mesenteric arteries (MA) of MWF-C as compared to W-C. FIN treatment significantly lowered β-index, a measure of intrinsic stiffness independent of geometry, in MWF (βMWF-FIN = 7.7 ± 0.4 vs. βMWF-C = 9.2 ± 0.5, p < 0.05) positively correlating with urinary albumin excretion. Elastin fenestrae area in the internal elastic lamina of MA from MWF-FIN was significantly larger (+377%, p < 0.05). FIN increased plasma pro-MMP-2 and decreased plasma MMP-2 and MMP-9 activities, correlating with reductions in β-index. MA from MWF-FIN exhibited higher NO bioavailability and reduced superoxide anion levels compared to MWF-C. Conclusion: FIN treatment reduces intrinsic arterial stiffness in MA from MWF rats associated with changes in elastin organization, normalization of MMP-2 and MMP-9 activities, and reduction of oxidative stress. Moreover, reduction of arterial stiffness correlates with reduction in albuminuria.

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 Endothelial Dysfunction in Chronic Kidney Disease, from Biology to Clinical Outcomes: A 2020 Update

2020 ◽  
Vol 9 (8) ◽  
pp. 2359 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Francesca Mallamaci ◽  
Carmine Zoccali
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Inflammatory Responses ◽  
Fibroblast Growth Factor 23 ◽  
Active Form ◽  
High Risk Population ◽  
Advanced Phase ◽  
No Bioavailability

The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of atherosclerosis and cardiovascular disease. Reduced nitric oxide (NO) bioavailability is a hallmark of chronic kidney disease (CKD), with this disturbance being almost universal in patients who reach the most advanced phase of CKD, end-stage kidney disease (ESKD). Low NO bioavailability in CKD depends on several mechanisms affecting the expression and the activity of endothelial NO synthase (eNOS). Accumulation of endogenous inhibitors of eNOS, inflammation and oxidative stress, advanced glycosylation products (AGEs), bone mineral balance disorders encompassing hyperphosphatemia, high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23), and low levels of the active form of vitamin D (1,25 vitamin D) and the anti-ageing vasculoprotective factor Klotho all impinge upon NO bioavailability and are critical to endothelial dysfunction in CKD. Wide-ranging multivariate interventions are needed to counter endothelial dysfunction in CKD, an alteration triggering arterial disease and cardiovascular complications in this high-risk population.

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 The effect of L-arginine on arterial stiffness and oxidative stress in chronic kidney disease

2012 ◽  
Vol 22 (5) ◽  
pp. 340 ◽  
Author(s):  
Sk Annavarajula ◽  
KV Dakshinamurty ◽  
M. U. R. Naidu ◽  
CPrabhakar Reddy
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
And Oxidative Stress

scholarly journals MP119INFLUENCE OF PROTEINURIA ON ENDOTHELIAL DYSFUNCTION AND ARTERIAL STIFFNESS IN CHRONIC KIDNEY DISEASE

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii471-iii472
Author(s):  
Vagner Meira ◽  
Mário Neves ◽  
Cláudio Loivos ◽  
Carla Lemos ◽  
Márcia Klein ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Arterial Stiffness
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