Endothelial dysfunction in patients with chronic kidney disease: prognostic potential of endothelin-1

Nephrology ◽  
2021 ◽  
Vol 4_2021 ◽  
pp. 8-15
Author(s):  
M.Z. Gasanov Gasanov ◽  
M.G. Panchenko Panchenko ◽  
M.M. Batyushin Batyushin ◽  
N.A. Bronovitskaya Bronovitskaya ◽  
A.V. Razina Razina ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Endothelin 1

scholarly journals Microelemental Status In Chronic Kidney Disease

2021 ◽  
Vol 03 (04) ◽  
pp. 184-188
Author(s):  
Razhabov Nodir Mukhammedovich ◽  
◽  
Akhmedova Nilufar Sharipovna ◽  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Serum Magnesium ◽  
Blood Pressure Level ◽  
Stage Iii ◽  
Endothelin 1 ◽  
Ckd Stage ◽  
Elemental Status

Evaluation of markers of endothelial dysfunction (endothelin-1 and nitric oxide) and elemental status (zinc, iron, magnesium) of chronic kidney disease (CKD). The study includes 104 patients with different stages of CKD: 63 patients with I stage of CKD, and 26 patients with CKD stage III and 15 patients with CKD V stage. Results: in patients with CKD, endothelin-1 increased with simultaneous decrease in production of nitric oxide in the progression of CKD from I to V stage. The increase of the content of endothelin-1 by 2.5 times determined in patients with stage V CKD, which was accompanied by a decline of the ratio of the concentrations of NO/ET-1 by 5.5 times. In patients with CKD, elemental status impairments were detected, manifested by a decrease in the content of zinc, iron, and magnesium in the serum of blood at the first stage, with the maximum implementation in stage III CKD. Hypertension was detected in 68.3% of patients with CKD. Direct correlations were found between the content of serum iron and magnesium with the level of arterial pressure in patients with stage I CKD. In III and V stage CKD, a direct correlation of serum magnesium with blood pressure level and nitric oxide concentration was established. Conclusion: children with CKD have endothelial dysfunction and elemental status disorders, beginning with the first stage of CKD development, which can be considered as factors determining the progression of the pathological process in the kidneys.

scholarly journals Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis: a randomized clinical trial

2020 ◽  
Author(s):  
Dominique M. Bovée ◽  
Lodi C. W. Roksnoer ◽  
Cornelis van Kooten ◽  
Joris I. Rotmans ◽  
Liffert Vogt ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Sodium Chloride ◽  
Kidney Disease ◽  
Sodium Bicarbonate ◽  
Renin Angiotensin System ◽  
Ammonium Excretion ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Endothelin 1 ◽  
Plasma Bicarbonate

Abstract Background Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis. Methods Patients with CKD stage G4 and plasma bicarbonate 15–24 mmol/l were randomized to receive sodium bicarbonate (3 × 1000 mg/day, ~ 0.5 mEq/kg), sodium chloride (2 × 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed. Results Forty-five patients were included (62 ± 15 years, eGFR 21 ± 5 ml/min/1.73m2, plasma bicarbonate 21.7 ± 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or α1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and α1-microglobulin (all P < 0.05). Conclusions Despite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity. Graphic abstract

Abstract 346: Mice Overexpressing Renin: a New Model of Progressive Chronic Kidney Disease

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Anne-Cecile Huby ◽  
Ahmed Abed ◽  
Panos Kavvadas ◽  
Carlo Alfieri ◽  
Maria-Pia Rastaldi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cell Adhesion ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Renal Disease ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Filtration Barrier ◽  
Human Pathology ◽  
Cell Adhesion Molecule 1

Background: Hypertension-induced chronic kidney disease in mouse models is quite fast and consequently away from the human pathology. There is an increasing need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. Aim: Our objective was dual: to investigate whether mice overexpressing renin ectopically at constant and high levels by genetic clamping (RenTg) could mimic kinetics and the physiopathological characteristics of hypertension-induced CKD and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD. Results: We found that RenTg mice are hypertensive (123±7 vs to 90±2 mm Hg for the wt age-matched animals, p<0.05) and slightly albuminuric (22.1±5.3 vs. 5.2±0.4 g/mol, p<0.01) as early as 3 month old. At this age, the expressions of adhesion markers such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 are 4-5 fold increased in the renal cortical vasculature indicating the beginning of endothelial dysfunction. Five month-old RenTg mice show perivascular and periglomerular infiltrations of macrophages and their GFR is starting to decrease(-10%). At 8 months, the renal cortex of RenTg mice is altered by leukocyte invasion, decreased expression of nephrin (a protein controlling filtration barrier), increased expression of KIM-1 (a protein typical of tubular cell stress) and of several pro-fibrotic agents of the TGFbeta family, and establishment of fibrotic lesions. At the age of 12 months, RenTg mice display several lesions of renal structure typical of hypertensive renal disease (such as glomerular ischemia, glomerulo- and nephroangio-sclerosis, mesangial expansion, tubular dilation), important proteinuria (138±20 g/mol) and a 55% fall of GFR. Conclusions: The RenTg strain develops progressively with age CKD. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide a useful tool allowing to gain new insights into the mechanisms of chronic renal failure and to identify new targets for arresting and/or reversing the development of 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 Statins and antiplatelet agents are associated with changes in the circulatory markers of endothelial dysfunction in chronic kidney disease

2019 ◽  
Vol 39 (3) ◽  
pp. 287-293
Author(s):  
Estefanya García Menéndez ◽  
María Marques Vidas ◽  
Matilde Alique ◽  
Julia Carracedo ◽  
Patricia de Sequera ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Antiplatelet Agents

scholarly journals Syndecan-1 and Free Indoxyl Sulfate Levels Are Associated with miR-126 in Chronic Kidney Disease

2021 ◽  
Vol 22 (19) ◽  
pp. 10549
Author(s):  
Ophélie Fourdinier ◽  
Griet Glorieux ◽  
Benjamin Brigant ◽  
Momar Diouf ◽  
Anneleen Pletinck ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Internal Control ◽  
Univariate Analysis ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Endothelial Glycocalyx ◽  
Correlated Parameters

Chronic kidney disease (CKD) is a major cause of death worldwide and is associated with a high risk for cardiovascular and all-cause mortality. In CKD, endothelial dysfunction occurs and uremic toxins accumulate in the blood. miR-126 is a regulator of endothelial dysfunction and its blood level is decreased in CKD patients. In order to obtain a better understanding of the physiopathology of the disease, we correlated the levels of miR-126 with several markers of endothelial dysfunction, as well as the representative uremic toxins, in a large cohort of CKD patients at all stages of the disease. Using a univariate analysis, we found a correlation between eGFR and most markers of endothelial dysfunction markers evaluated in this study. An association of miR-126 with all the evaluated uremic toxins was also found, while uremic toxins were not associated with the internal control, specifically cel-miR-39. The correlation between the expression of endothelial dysfunction biomarker Syndecan-1, free indoxyl sulfate, and total p-cresyl glucuronide on one side, and miR-126 on the other side was confirmed using multivariate analysis. As CKD is associated with reduced endothelial glycocalyx (eGC), our results justify further evaluation of the role of correlated parameters in the pathophysiology of CKD.

Abstract P099: The Relation of Kidney Disease to Measures of Digital Arterial Tonometry in the Jackson Heart Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Eric McClendon ◽  
Solomon Musani ◽  
Sushante Khaire ◽  
Herman Taylor ◽  
Ervin Fox
Keyword(s):  
Chronic Kidney Disease ◽  
African Americans ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Least Square ◽  
Jackson Heart Study ◽  
Pulse Wave Amplitude ◽  
Arterial Tonometry ◽  
Heart Study ◽  
Age And Sex

Background: The presence of chronic kidney disease is greater in African Americans than in non-Hispanic whites. Though there is data to show a relation between endothelial dysfunction and end-stage kidney disease, the relation to mild and moderate chronic kidney disease (particularly in African Americans) is unclear. Methods and Results: Digital arterial tonometry was performed during Exam 2 and 3 of the Jackson Heart Study using the endoPAT2000. Data from digital arterial tonometry included baseline pulse wave amplitude (BPA) as a measure of endothelial tone and reactive hyperemic index (F-RHI) as a measure of endothelial function. For this study, the estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation. Those participants with eGFR < 60 ml/min/1.73m2 were defined as having CKD. Participants with eGFR < 15 ml/min/1.73m2 were excluded from the analysis. Microalbuminuria in this study was defined as a urinary albumin:creatinine ratio ≥ 17mg/g in men and ≥ 25 mg/g in women. We compared the differences in least square means adjusted for age and sex, and adjusted for multiple traditional clinical covariates using a generalized linear model. Results: There were 834 participants in the study population (mean age 58.5 years, 61% women); 87 (10.4%) participants with CKD and 108 (13.0%) with microalbuminuria. In age and sex adjusted samples, we found that both BPA and F-RHI were significantly associated with CKD in the pooled samples. However in multivariable adjusted analysis the relation was no longer significant in either the pooled or sex-specific samples. In the multivariable adusted analysis,BPA was significantly (P=0.036) associated with microalbuminuria in men and F-RHI was weakly significantly (P=0.08) associated with microalbuminuria in women. Conclusion: We found that endothelial dysfunction as measured by digital arterial tonometry is not significantly associated with chronic kidney disease. There is an association of endothelial tone in men and endothelial dysfunction in women with microalbuminuria.

scholarly journals Antioxidant and Anti-Inflammatory Strategies Based on the Potentiation of Glutathione Peroxidase Activity Prevent Endothelial Dysfunction in Chronic Kidney Disease

2018 ◽  
Vol 51 (3) ◽  
pp. 1287-1300 ◽  
Author(s):  
Manel Vera ◽  
Sergi Torramade-Moix ◽  
Susana Martin-Rodriguez ◽  
Aleix Cases ◽  
Josep M. Cruzado ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Glutathione Peroxidase ◽  
Antioxidant Properties ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Oxygen Species ◽  
Radical Oxygen Species ◽  
Anti Inflammatory

Background/Aims: Accelerated atherosclerosis in chronic kidney disease (CKD) is preceded by endothelial dysfunction (ED), which exhibits a proinflammatory and prothrombotic phenotype and enhanced oxidative stress. In this study, the effect of several compounds with anti-inflammatory and/or antioxidant properties on uremia-induced endothelial dysfunction has been evaluated in an in vitro model. Methods: Endothelial cells (ECs) were exposed to sera from uremic patients in the absence and presence of the flavonoids apigenin, genistein and quercetin, the antioxidant enzyme mimetics (AEM) ebselen (glutathione peroxidase mimetic), EUK-134 and EUK-118 (both superoxide dismutase mimetics), and the pharmacological drug N-acetylcysteine (NAC). We explored changes in the expression of adhesion receptors on the cell surface, by immunofluorescence, the production of radical oxygen species (ROS), by fluorescence detection, and the activation of signaling proteins related to inflammation, by both a phosphospecific antibody cell-based ELISA and immunoblotting techniques. Results: Uremic media induced a significantly increased expression of ICAM-1, overproduction of radical oxygen species (ROS) and activation of p38 mitogen activated protein kinase (p38MAPK) and Nuclear Factor kB (NFkB) in ECs. Quercetin, the AEM and NAC showed a significant inhibitory effect on both ICAM-1 expression and ROS generation (p<0.05). All the compounds reduced p38MAPK activation, but only the AEM, especially ebselen, and NAC, both potentiating the glutathione peroxidase pathway, also inhibited NFkB activation. These two compounds were capable of increasing endothelial glutathione levels, especially in response to uremia. Conclusion: Our results indicate that the potentiation of the antioxidant pathways can be an effective strategy to improve endothelial dysfunction in uremia and a potential target to reduce the cardiovascular risk in this population.

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