Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update

Toxins, Journal Year: 2018, Volume and Issue: 10(1), P. 33 - 33

Published: Jan. 8, 2018

In this narrative review, the biological/biochemical impact (toxicity) of a large array known individual uremic retention solutes and groups is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble or groups, protein bound middle molecules. All but one solute (glomerulopressin) affected at least mechanism with potential to contribute syndrome. general, several mechanisms were influenced for each group solutes, some impacting up 7 different biological systems 11 considered. The inflammatory, cardio-vascular fibrogenic those most frequently they are by major actors in high morbidity mortality CKD also that have been studied. A scoring system was built intention classify reviewed according experimental evidence toxicity (number affected) overall clinical evidence. Among highest globally 3 [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl indole acetic acid; kynurenines; phenyl acid;] molecules [β2-microglobulin; ghrelin; parathyroid hormone). more data provided almost half them missing spite robust data. picture emanating complex disorder, where multiple factors multisystem complication profile, so it seems not much use pursue decrease concentration single compound.

Language: Английский

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High Amylose Resistant Starch Diet Ameliorates Oxidative Stress, Inflammation, and Progression of Chronic Kidney Disease

PLoS ONE, Journal Year: 2014, Volume and Issue: 9(12), P. e114881 - e114881

Published: Dec. 9, 2014

Inflammation is a major mediator of CKD progression and partly driven by altered gut microbiome intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting dominance urease-possessing bacteria; disruption epithelial urea-derived ammonia leading to endotoxemia bacterial translocation; restriction potassium-rich fruits vegetables common sources fermentable fiber. Restriction these foods leads depletion bacteria that convert indigestible carbohydrates short chain fatty acids important nutrients for colonocytes regulatory T lymphocytes. We hypothesized high resistant starch diet attenuates progression. Male Sprague Dawley rats were fed chow containing 0.7% adenine 2 weeks induce CKD. Rats then diets supplemented with amylopectin (low-fiber control) or fiber (amylose maize starch, HAM-RS2) 3 weeks. consuming low exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation NFkB, upregulation pro-inflammatory, pro-oxidant, pro-fibrotic molecules; impaired Nrf2 activity, down-regulation antioxidant enzymes, colonic tight junction. The significantly attenuated abnormalities. Thus retards oxidative stress inflammation rats. Future studies needed explore impact HAM-RS2 patients.

Language: Английский

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Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats

AJP Renal Physiology, Journal Year: 2016, Volume and Issue: 310(9), P. F857 - F871

Published: Feb. 11, 2016

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts microbial composition, increased fecal pH, blood levels of microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter milieu CKD rat models leads markedly improved function. aim present study was identify specific cecal bacteria cecal, blood, urinary that associate changes function potential mechanisms involved amelioration response resistant starch. Male Sprague-Dawley rats adenine-induced were fed a semipurified low-fiber diet or high-fiber [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). microbiome characterized, contents, serum, urine analyzed. HAMRS2-fed displayed decreased diversity, an Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes altered urine, many which had strong correlations abundances, i.e., serum indoxyl sulfate reduced by 36% 66%, respectively, p-cresol 47% rats. Outcomes from this coincident improvements indexes outcomes previously reported these rats, suggesting important role microbial-derived factors microbe metabolism regulating host

Language: Английский

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Protein Nutrition and Malnutrition in CKD and ESRD

Nutrients, Journal Year: 2017, Volume and Issue: 9(3), P. 208 - 208

Published: Feb. 27, 2017

Elevated protein catabolism and malnutrition are common in patients with chronic kidney disease (CKD) end‐stage renal (ESRD). The underlying etiology includes, but is not limited to, metabolic acidosis intestinal dysbiosis; systemic inflammation activation of complements, endothelin‐1 renin‐angiotensin‐aldosterone (RAAS) axis; anabolic hormone resistance; energy expenditure elevation; uremic toxin accumulation. All these derangements can further worsen function, leading to poor patient outcomes. Many CKD‐related be prevented substantially reversed, representing an area great potential improve CKD ESRD care. This review integrates known information recent advances the nutrition ESRD. Management recommendations summarized. Thorough understanding pathogenesis will undoubtedly facilitate design development more effective strategies optimize

Language: Английский

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Gut microbiome in chronic kidney disease: challenges and opportunities

Translational research, Journal Year: 2016, Volume and Issue: 179, P. 24 - 37

Published: May 1, 2016

Language: Английский

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Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets

Toxins, Journal Year: 2021, Volume and Issue: 13(2), P. 142 - 142

Published: Feb. 13, 2021

Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in function leads to an accumulation toxins normally cleared by the kidneys, resulting uremia. Uremic are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound and middle molecules. CKD patients have increased risk developing cardiovascular (CVD), due assortment CKD-specific factors. uremic circulation tissues associated with progression its co-morbidities, including CVD. Although numerous been identified date many them believed play role CVD, very few extensively studied. pathophysiological mechanisms must be investigated further for better understanding their roles develop therapeutic interventions against toxicity. This review discusses toxicity indoxyl sulfate, p-cresyl hippuric acid, TMAO, ADMA, TNF-α, IL-6. A focus also placed on potential targets

Language: Английский

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Probiotics and chronic kidney disease

Kidney International, Journal Year: 2015, Volume and Issue: 88(5), P. 958 - 966

Published: Sept. 16, 2015

Language: Английский

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Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases

Clinical & Translational Immunology, Journal Year: 2016, Volume and Issue: 5(5)

Published: May 1, 2016

It is now convincingly clear that diet one of the most influential lifestyle factors contributing to rise inflammatory diseases and autoimmunity in both developed developing countries. In addition, modern 'Western diet' has changed recent years with increased caloric intake, changes relative amounts dietary components, including lower fibre higher levels fat poor quality carbohydrates. Diet shapes large‐bowel microbial ecology, this may be highly relevant human diseases, as gut microbiota composition are associated many diseases. Recent studies have demonstrated a remarkable role for diet, their metabolites—the short‐chain fatty acids (SCFAs)—in pathogenesis several such asthma, arthritis, bowel disease, colon cancer wound‐healing. This review summarizes how metabolites (particularly SCFAs) can modulate progression autoimmunity, reveal molecular mechanisms (metabolite‐sensing G protein‐coupled receptor (GPCRs) inhibition histone deacetylases (HDACs)). Therefore, considerable benefit could achieved simply through use probiotics prevention treatment autoimmunity.

Language: Английский

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Gut–organ axis: a microbial outreach and networking

Letters in Applied Microbiology, Journal Year: 2020, Volume and Issue: 72(6), P. 636 - 668

Published: May 30, 2020

Human gut microbiota (GM) includes a complex and dynamic population of microorganisms that are crucial for well‐being survival the organism. It has been reported as diverse relatively stable with shared core microbiota, including Bacteroidetes Firmicutes major dominants. They key regulators body homeostasis, involving both intestinal extra‐intestinal effects by influencing many physiological functions such metabolism, maintenance barrier inflammation hematopoiesis. Any alteration in GM community structures not only trigger disorders but also influence other organs cause associated diseases. In recent past, defined 'vital organ' its involvement organs; thus, establishing link or bi‐ multidirectional communication axis between via neural, endocrine, immune, humoral metabolic pathways. Alterations have linked to several diseases known humans; although exact interaction mechanism is yet be defined. this review, bidirectional relationship vital human was envisaged discussed under headings. Furthermore, disease symptoms were revisited redefine network microbes organs. Significance Impact Study: Gut metabolites play role maintaining health various Literature review evidences suggest any composition diversity triggers influences cause‐associated we attempted provide readers broad overview connection Our effort will foster development personalized treatment can adopted evolved targeting microbiome deliberately controlled manner.

Language: Английский

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Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS–based metabolomics approach

Kidney International, Journal Year: 2017, Volume and Issue: 92(3), P. 634 - 645

Published: April 8, 2017

Gut microbiota is involved in the metabolism of uremic solutes. However, precise influence to retention solutes CKD obscure. To clarify this, we compared adenine-induced renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining metabolite profiles plasma, feces, urine using a capillary electrophoresis time-of-flight mass spectrometry-based approach. Mice with conditions demonstrated significant changes plasma metabolites. Among 183 detected solutes, levels 11 including major toxins, were significantly lower than SPF failure. These considered microbiota-derived included indoxyl sulfate, p-cresyl phenyl cholate, hippurate, dimethylglycine, γ-guanidinobutyrate, glutarate, 2-hydroxypentanoate, trimethylamine N-oxide, phenaceturate. Metabolome profiling showed that these classified into three groups depending on their origins: completely derived from (indoxyl sulfate), both host (dimethylglycine), dietary components (trimethylamine N-oxide). Additionally, resulted disappearance colonic short-chain fatty acids, decreased utilization intestinal amino more severe damage Microbiota-derived acids efficient acid may have renoprotective effect, loss factors exacerbate Thus, contributes substantially production harmful but conversely, growth without has effects progression.

Language: Английский

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