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

Gouroju, S.; Rao, Pragna; Bitla, Aparna R.; Vinapamula, Kiranmayi S; Manohar, Suchitra M.; Vishnubhotla, Sivakumar

doi:10.4103/ijn.ijn_71_17

Cited by 28 publications

(17 citation statements)

References 33 publications

(39 reference statements)

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“…These results are in line with a different study showing higher TAC in a rat model of AKI than in sham-operated animals [52]. Another study involving CKD patients has shown higher FRAP concentrations in patients than in controls [53]. In addition, urinary FRAP levels were also elevated in 5/6 Nex, confirming the situation observed in plasma.…”

Section: Discussionsupporting

confidence: 88%

Oxidative Stress in Animal Models of Acute and Chronic Renal Failure

et al. 2019

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Introduction. Kidney disease is a worldwide health and economic burden, with rising prevalence. The search for biomarkers for earlier and more effective disease screening and monitoring is needed. Oxidative stress has been linked to both, acute kidney injury (AKI) and chronic kidney disease (CKD). The aim of our study was to investigate whether the concentrations of systemic markers of oxidative stress and antioxidant status are affected by AKI and CKD, and to identify potential biomarkers. Methods. In adult male Wistar rats, AKI was induced by bilateral nephrectomy, and CKD was induced by 5/6 nephrectomy. Blood was collected 48 hours after surgery in AKI and 6 months after surgery in CKD. Advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGEs), fructosamine, total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP) were measured. Results. Impaired renal function was confirmed by high concentrations of plasma creatinine and urea in AKI and CKD animals. AOPP and fructosamine were higher by 100% and 54% in AKI, respectively, and by 100% and 199% in CKD, respectively, when compared to corresponding control groups. Similarly, there was approximately a twofold increase in AGEs (by 92%) and TAC (by 102%) during AKI. In CKD, concentrations of FRAP, as an antioxidative status marker, were doubled (by 107%) when compared to the control group, but concentration of TAC, another marker of antioxidative status, did not differ between the groups. Conclusions. AKI and CKD led to increased systemic oxidative stress. AOPP and fructosamine could be considered potential biomarkers for both, acute and chronic kidney damage. On the other hand, AGEs, TAC, and FRAP seem to be disease specific, which could help to differentiate between acute and chronic kidney injuries. However, this needs further validation in clinical studies.

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Section: Discussionsupporting

confidence: 88%

Oxidative Stress in Animal Models of Acute and Chronic Renal Failure

et al. 2019

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“…By contrast, in advanced CKD, the elevated levels of circulating UTs may promote atherosclerotic calcification and be responsible for the development of Monckeberg’s medial calcification. Several UTs (notably indoxyl sulphate (IS) and paracresyl sulphate (pCS)) display pro-inflammatory properties, and their serum concentrations are correlated with inflammatory markers in patients with CKD [103]. Some of these inflammatory markers (such as TNF-α, IL-6 and IL-1β) are themselves classified as UTs [104].…”

Section: The Impact Of Ckd On Macrophage Functions: Consequences Fmentioning

confidence: 99%

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

Hénaut¹,

Candellier

Boudot³

et al. 2019

Toxins

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Cardiovascular disease (CVD) is an important cause of death in patients with chronic kidney disease (CKD), and cardiovascular calcification (CVC) is one of the strongest predictors of CVD in this population. Cardiovascular calcification results from complex cellular interactions involving the endothelium, vascular/valvular cells (i.e., vascular smooth muscle cells, valvular interstitial cells and resident fibroblasts), and monocyte-derived macrophages. Indeed, the production of pro-inflammatory cytokines and oxidative stress by monocyte-derived macrophages is responsible for the osteogenic transformation and mineralization of vascular/valvular cells. However, monocytes/macrophages show the ability to modify their phenotype, and consequently their functions, when facing environmental modifications. This plasticity complicates efforts to understand the pathogenesis of CVC—particularly in a CKD setting, where both uraemic toxins and CKD treatment may affect monocyte/macrophage functions and thereby influence CVC. Here, we review (i) the mechanisms by which each monocyte/macrophage subset either promotes or prevents CVC, and (ii) how both uraemic toxins and CKD therapies might affect these monocyte/macrophage functions.

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“…Here we review gut-derived, protein-bound uremic toxins, separating them into two categories: (1) diet-ingested toxins and (2) toxins generated by gut microbial metabolism. Both PBUT categories impact gut microflora composition, and the intake, intestinal absorption, and serum levels of these toxins are altered with each progressing stage of kidney disease [ 20 ]. We outline the derivation and pathological mechanisms of each class of gut-derived PBUT, as well as their relationship to the gut microbiota, and we present recent approaches to reduce PBUT levels by targeting the gut microbiome.…”

Section: Introductionmentioning

confidence: 99%

Gut-Derived Protein-Bound Uremic Toxins

Graboski

Redinbo

2020

Toxins

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Chronic kidney disease (CKD) afflicts more than 500 million people worldwide and is one of the fastest growing global causes of mortality. When glomerular filtration rate begins to fall, uremic toxins accumulate in the serum and significantly increase the risk of death from cardiovascular disease and other causes. Several of the most harmful uremic toxins are produced by the gut microbiota. Furthermore, many such toxins are protein-bound and are therefore recalcitrant to removal by dialysis. We review the derivation and pathological mechanisms of gut-derived, protein-bound uremic toxins (PBUTs). We further outline the emerging relationship between kidney disease and gut dysbiosis, including the bacterial taxa altered, the regulation of microbial uremic toxin-producing genes, and their downstream physiological and neurological consequences. Finally, we discuss gut-targeted therapeutic strategies employed to reduce PBUTs. We conclude that targeting the gut microbiota is a promising approach for the treatment of CKD by blocking the serum accumulation of PBUTs that cannot be eliminated by dialysis.

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

Cited by 28 publications

References 33 publications

Oxidative Stress in Animal Models of Acute and Chronic Renal Failure

Oxidative Stress in Animal Models of Acute and Chronic Renal Failure

New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease

Gut-Derived Protein-Bound Uremic Toxins

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