Role of gut-derived uremic toxins on oxidative stress and inflammation in patients with chronic kidney disease

Background: Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. Methods: We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Results: Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. Conclusions: In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

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

International Journal of Molecular Sciences ◽

10.3390/ijms221910549 ◽

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.

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Uremic toxins, oxidative stress, and inflammation in chronic kidney disease

Journal of Renal Nutrition and Metabolism ◽

10.4103/jrnm.jrnm_57_19 ◽

2019 ◽

Vol 5 (2) ◽

pp. 48

Author(s):

Ratan Jha ◽

KiranKumar Mukku

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Uremic Toxins

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

Toxins ◽

10.3390/toxins10090367 ◽

2018 ◽

Vol 10 (9) ◽

pp. 367 ◽

Cited By ~ 38

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.

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The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis

Journal of Cellular Physiology ◽

10.1002/jcp.27797 ◽

2018 ◽

Vol 234 (7) ◽

pp. 11411-11423 ◽

Cited By ~ 7

Author(s):

Mohammad Khabbaz Shirazi ◽

Asaad Azarnezhad ◽

Mohammad Foad Abazari ◽

Mansour Poorebrahim ◽

Pegah Ghoraeian ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Chronic Kidney Disease ◽

Hydrogen Sulfide ◽

Kidney Disease ◽

Nitric Oxide Signaling

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Impact of the oral adsorbent AST-120 on oxidative stress and uremic toxins in high-risk chronic kidney disease patients

International Journal of Cardiology ◽

10.1016/j.ijcard.2014.09.196 ◽

2014 ◽

Vol 177 (2) ◽

pp. 705-707 ◽

Cited By ~ 5

Author(s):

Shigeru Toyoda ◽

Migaku Kikuchi ◽

Takaaki Komatsu ◽

Yuichi Hori ◽

Shiro Nakahara ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

High Risk ◽

Kidney Disease ◽

Uremic Toxins ◽

Oral Adsorbent

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Role of matrix metalloproteinase-9 in chronic kidney disease: a new biomarker of resistant albuminuria

Clinical Science ◽

10.1042/cs20150517 ◽

2016 ◽

Vol 130 (7) ◽

pp. 525-538 ◽

Cited By ~ 26

Author(s):

Helena Pulido-Olmo ◽

Concha F. García-Prieto ◽

Gloria Álvarez-Llamas ◽

María G. Barderas ◽

Fernando Vivanco ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 9 ◽

Metalloproteinase 9

Resistant albuminuria developed under chronic RAS blockade is strongly associated with increased circulating MMP-9 activity mediated by oxidative stress.

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