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.

scholarly journals SP620ANTIOXIDANT AND ANTIINFLAMMATORY STRATEGIES TO PREVENT ENDOTHELIAL DYSFUNCTION IN CHRONIC KIDNEY DISEASE: THE ROLE OF N-ACETYL CYSTEINE

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i302-i302
Author(s):  
Aleix Cases ◽  
Manel Vera ◽  
Marta Palomo ◽  
Susana Martin-Rodriguez ◽  
Josep Maria Cruzado ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Acetyl Cysteine

scholarly journals Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 367 ◽  
Author(s):  
Wen-Chih Liu ◽  
Yasuhiko Tomino ◽  
Kuo-Cheng Lu
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Large Scale ◽  
Interstitial Fibrosis ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Inflammatory Reactions

Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

scholarly journals P0921ROLE OF UREMIC TOXIN, INDOXYL SULFATE IN SARCOPENIA OF NONDIALYSIS DEPENDENT-CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jun Chul Kim ◽  
Seok Hui Kang ◽  
Miyeun Han ◽  
Su-Hyun Kim ◽  
Ran-Hui Cha ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Mass ◽  
Bioelectrical Impedance ◽  
Impedance Analysis ◽  
Indoxyl Sulfate ◽  
High Rate ◽  
Uremic Toxin ◽  
Inverse Association

Abstract Background and Aims Sarcopenia in patients with chronic kidney disease (CKD) is highly prevalent and leads to high rate of morbidity and mortality. The role of indoxyl sulfate (IS) to develop muscle wasting has been researched and proved in several animal model studies. However, there is no human data showing this relationship in CKD population. The aim of the present study was to evaluate the association between serum IS levels and each component of sarcopenia in nondialysis dependent-CKD (NDD-CKD) patients. Method We enrolled 150 NDD-CKD adult patients from 6 medical centers and collected data of demographics, blood chemistry such as indoxyl sulfate, interleukin (IL)-6, and estimated glomerular filtration rate using MDRD equation (eGFR), and body mass index (BMI, kg/m2). We also measured hand-grip strength (HGS, kg), walking speed (WS, m/s), skeletal muscle mass (SMM, kg) by bioelectrical impedance analysis (BIA). Results The numbers of male sex was 97 (64.7%). Mean age was 63.7±10.8 years old. The numbers of patients with diabetes mellitus was 77 (52.0%). Charlson comorbidity index (CCI) score was 3.9 ± 1.9. The stage of CKD ranged from 3 to 5 (eGFR=33.7±12.0 ml/min/1.73m2, mean±SD). Correlation coefficients with indoxyl sulfate levels were 0.211 for serum IL-6 level (P = 0.010), -0.212 for HGS (P = 0.009), -0.188 for WS (P = 0.021), -0.237 for SMM (P = 0.004), and -0.168 for BMI (P = 0.041), respectively. Correlation analysis showed that indoxyl sulfate levels had inverse association significantly with HGS, WS, SMM, and BMI and were positively associated with serum IL-6 levels. Conclusion Our study shows that higher serum indoxyl sulfate level was significantly associated with lower levels of muscle mass, strength, and physical performance function and higher inflammation status in non-dialysis dependent CKD patients. We suggest that the role of AST120 in prevention or treatment of sarcopenia be studied in this CKD population.

scholarly journals Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic Toxins

Nephron ◽  
2017 ◽  
Vol 137 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jessyca S. Brito ◽  
Natália A. Borges ◽  
Marta Esgalhado ◽  
D''Angelo C. Magliano ◽  
Christophe O. Soulage ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Uremic Toxins ◽  
Aryl Hydrocarbon

scholarly journals Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model

2018 ◽  
Vol 315 (4) ◽  
pp. F824-F833 ◽  
Author(s):  
Eikan Mishima ◽  
Shinji Fukuda ◽  
Yoshitomi Kanemitsu ◽  
Daisuke Saigusa ◽  
Chikahisa Mukawa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Kidney Disease ◽  
Therapeutic Option ◽  
Short Chain Fatty Acids ◽  
Inhibitory Effect ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Vehicle Group ◽  
Microbiota Composition

Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins, including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium-glucose cotransporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice. Two-week canagliflozin (10 mg/kg po) treatment did not influence the impaired renal function; however, it significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate in renal failure mice (a 75% and 26% reduction, respectively, compared with the vehicle group). Additionally, canagliflozin significantly increased cecal short-chain fatty acids in the mice, suggesting the promotion of bacterial carbohydrate fermentation in the intestine. Analysis of the cecal microbiota showed that canagliflozin significantly altered microbiota composition in the renal failure mice. These results indicate that canagliflozin exerts intestinal effects that reduce the accumulation of uremic toxins including p-cresyl sulfate. Reduction of accumulated uremic toxins by canagliflozin could provide a potential therapeutic option in chronic kidney disease.

Role of Uremic Toxins and Oxidative Stress in the Development of Chronic Kidney Disease–Mineral and Bone Disorder

2012 ◽  
Vol 22 (1) ◽  
pp. 98-101 ◽  
Author(s):  
Hisae Tanaka ◽  
Hirotaka Komaba ◽  
Masahiro Koizumi ◽  
Takatoshi Kakuta ◽  
Masafumi Fukagawa
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Uremic Toxins ◽  
Mineral And Bone Disorder ◽  
Bone Disorder ◽  
And Oxidative Stress

scholarly journals Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Toxins ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 688
Author(s):  
Kullaya Takkavatakarn ◽  
Pongpratch Puapatanakul ◽  
Jeerath Phannajit ◽  
Warumphon Sukkumme ◽  
Pajaree Chariyavilaskul ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Randomized Controlled Trial ◽  
Calcium Carbonate ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Total Serum ◽  
Randomized Controlled ◽  
Significant Difference

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.

scholarly journals Indoxyl sulfate has a dominant role regarding the risks during different stages of chronic kidney disease

2020 ◽  
Author(s):  
Cheng-Hsu Chen ◽  
Shih-Chien Huang ◽  
Pei-Chih Lin ◽  
Shang-Feng Tsai ◽  
Yi-Chia Huang
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Dominant Role ◽  
Plasma Homocysteine ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Antioxidant Enzyme Activities ◽  
Uremic Toxin ◽  
Ckd Stage

Abstract Background: Increased levels of uremic toxins and decreased antioxidant capacities have a significant impact on the progression of chronic kidney disease (CKD). However, it is unclear whether they interact with each other in order to mediate the damage of renal function. The purpose of this study was to determine whether uremic toxins [i.e., homocysteine and indoxyl sulfate (IS)] and glutathione-dependent antioxidant enzyme activities are dependently or independently associated with each other in affecting renal function during different stages of CKD patients.Methods: One hundred thirty-two patients diagnosed with CKD stage 1 to 5 participated in this cross-sectional study.Results: Patients who had reached an advanced CKD stage experienced a gradual increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activities. Plasma homocysteine, cysteine and IS concentrations were positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS and GSH-Px levels were significantly associated with renal function, only plasma IS levels still had a significant association with renal function after these parameters were simultaneously adjusted.Conclusions: IS plays a more dominant role than other factors in affecting renal function, where a higher IS concentration needs to be controlled in order to defer the progressive loss of renal function.

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