INTRODUCTION: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine-related factors on IS concentration. METHODS: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA) that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. RESULTS: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 μmol/L) in comparison with a wild-type genotype (360.5 μmol/L). CONCLUSION: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.
Indoxyl sulfát je intenzivně studovaný uremický toxin. Jedná se o malou molekulu, která vzniká z aminokyseliny tryptofanu působením střevních bakterií, v krvi je vázána z 90 % na plazmatické proteiny. Za fyziologického stavu je indoxyl sulfát z těla vylučován ledvinami, avšak v případě jejich poškození dochází k retenci indoxyl sulfátu v organismu. Indoxyl sulfát jako retinovaná látka zasahuje do celého organismu, podílí se na progresi imunitní dysfunkce, kardiovaskulárního poškození, kostních poruch, renální a srdeční fibrózy a dalších dysfunkcí a komplikací spojených s pokročilým onemocněním a selháním ledvin, s nejzávažnější manifestací u pacientů v dialyzačním programu. Vzhledem k tomu, že odstranění indoxyl sulfátu dialyzačními technikami je velmi obtížné a v nejlepším případě pouze částečné, je třeba hledat i jiné cesty k omezení vysoké koncentrace indoxyl sulfátu v plazmě pacientů s pokročilým renálním onemocněním, a zejména s renálním selháním.
Indoxyl sulfate is an intensively studied uremic toxin. It is a small molecule that is derived from the amino acid tryptophan by action of intestinal bacteria, in the blood 90 % of indoxyl sulfate is bound to plasma proteins. In physiological state, indoxyl sulfate is excreted from the body by the kidneys, however in the case of kidney damage indoxyl sulfate is retained in the body. Indoxyl sulfate as a retined substance affects the whole organism, it participates in the progression of immune dysfunction, cardiovascular damage, bone disorders, renal and cardiac fibrosis and others dysfunctions and complications associated with advanced renal disease and failure, with the most severe manifestation in patients in dialysis program. Because the removal of indoxyl sulfate by dialysis techniques is very difficult and at best only partial, other ways to limit the high plasma concentration of indoxyl sulfate in patients with advanced renal disease, especially with chronic kidney disease, should be sought
- MeSH
- chronické selhání ledvin komplikace MeSH
- dialýza ledvin MeSH
- indican * biosyntéza škodlivé účinky toxicita MeSH
- lidé MeSH
- střevní mikroflóra fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- chronické selhání ledvin * dietoterapie epidemiologie metabolismus MeSH
- indican škodlivé účinky MeSH
- kresoly škodlivé účinky MeSH
- lidé MeSH
- placeba terapeutické užití MeSH
- potravní vláknina terapeutické užití MeSH
- prebiotika MeSH
- škrob terapeutické užití MeSH
- střevní mikroflóra účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- randomizované kontrolované studie MeSH
Indoxyl sulfate has been identified as a major factor in the dysregulation of several genes. It is classified as a poorly dialyzable uremic toxin and thus a leading cause in the poor survival rate of dialysis patients. A monocentric, prospective, open cohort study was performed in 43 male patients undergoing chronic renal replacement therapy in a single hemodialysis center. The aim of the study was to determine the influence of acetate- versus citrate-buffered dialysis fluids in hemodialysis (HD) and postdilution hemodiafiltration (HDF) settings on the elimination of indoxyl sulfate. Also, additional factors potentially influencing the serum concentration of indoxyl sulfate were evaluated. For this purpose, the predialysis and postdialysis concentration ratio of indoxyl sulfate and total protein was determined. The difference was of 1.15 (0.61; 2.10), 0.89 (0.53; 1.66), 0.32 (0.07; 0.63), and 0.44 (0.27; 0.77) μmol/g in acetate HD and HDF and citrate HD and HDF, respectively. Acetate HD and HDF were superior when concerning IS elimination when compared to citrate HD and HDF. Moreover, residual diuresis was determined as the only predictor of lower indoxyl sulfate concentration, suggesting that it should be preserved as long as possible. This trial is registered with EU PAS Register of Studies EUPAS23714.
- MeSH
- acetáty farmakologie MeSH
- dialýza ledvin metody MeSH
- dialyzační roztoky chemie farmakologie MeSH
- hemodiafiltrace metody MeSH
- hydrogenuhličitany MeSH
- indican krev farmakokinetika MeSH
- kyselina citronová krev farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci ledvin terapie MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- MeSH
- acylkarnitin krev MeSH
- časové faktory MeSH
- chronická renální insuficience * krev MeSH
- dialýza ledvin metody MeSH
- estery kyseliny sírové krev MeSH
- indican krev MeSH
- kresoly krev MeSH
- lidé MeSH
- metabolom MeSH
- methylaminy krev MeSH
- prospektivní studie MeSH
- větvené aminokyseliny krev MeSH
- Check Tag
- lidé MeSH
- MeSH
- albuminurie MeSH
- biologické toxiny škodlivé účinky MeSH
- gastrointestinální trakt patofyziologie MeSH
- indican krev MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- renální insuficience * krev mikrobiologie MeSH
- rizikové faktory MeSH
- střevní mikroflóra * účinky léků MeSH
- synbiotika * MeSH
- Check Tag
- lidé MeSH
Pathogenesis of adenine-induced chronic renal failure may involve inflammatory, immunological and/or oxidant mechanisms. Gum arabic (GA) is a complex polysaccharide that acts as an anti-oxidant which can modulate inflammatory and/or immunological processes. Therefore, we tested here the effect of GA treatment (15 % in the drinking water for 4 weeks) in plasma and urine of rats, on a novel cytokine that has been shown to be pro-inflammatory, viz, DNA-binding high-mobility group box-1 protein (HMGB1). Adenine (0.75 % in the feed, 4 weeks) significantly increased indoxyl sulphate, urea and creatinine concentrations in plasma, and significantly decreased the creatinine clearance. GA significantly abated these effects. The concentrations of HMGB1 in urine before the start of the experiment were similar in all four groups. However, 24 h after the last treatment, adenine treatment increased significantly the concentration of HMGB1 when compared with the control. GA treatment did not affect the HMGB1 concentration in urine. Moreover, the concentration of HMGB1 in plasma obtained 24 h after the last treatment in rats treated with adenine was drastically reduced compared with the control group. This may explain its significant rise in urine. In conclusion, HMGB1 can be considered a potentially useful biomarker in adenine induced CRF and its treatment.
- MeSH
- adenin * MeSH
- arabská guma farmakologie MeSH
- biologické markery krev moč MeSH
- časové faktory MeSH
- chronické selhání ledvin chemicky indukované farmakoterapie metabolismus patofyziologie MeSH
- indican krev MeSH
- kreatinin krev MeSH
- ledviny účinky léků metabolismus patofyziologie MeSH
- mediátory zánětu krev metabolismus moč MeSH
- močovina krev MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- protein HMGB1 krev metabolismus moč MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Indoxyl sulfate (IS), a uremic toxin, is considered as a risk factor for accelerated atherosclerosis in patients with chronic kidney disease. As uptake of oxidized low-density lipoprotein (Ox-LDL) in macrophages is a key event in the progression of atherosclerosis, the aim of this study was to determine direct effects of IS on uptake of Ox-LDL in macrophages. Flow cytometric analysis revealed that IS significantly stimulated Ox-LDL uptake by THP-1 macrophages in both dose- and time-dependent manners. A CD36 inhibitor, sulfosuccinimidyl oleate (SSO), and ERK1/2 inhibitors, PD98059 and U0126, could suppress the IS-stimulated Ox-LDL uptake. IS also stimulated CD36 expression, which was inhibited by PD98059 and U0126. Western blotting analysis showed that IS significantly activated ERK1/2 mitogen-activated protein kinase (MAPK) pathway by increasing its phosphorylation level. Further, CCK-8 assay showed that IS exerted its effects without affecting cell viability. In conclusion, IS stimulated Ox-LDL uptake through up-regulation of CD36 expression in THP-1 macrophages, partly via ERK1/2 MAPK pathway. This might be one of the mechanisms underlying the progression of atherosclerosis in patients with chronic kidney disease.
- MeSH
- antigeny CD36 fyziologie MeSH
- ateroskleróza * patofyziologie MeSH
- chronická renální insuficience * komplikace MeSH
- extracelulárním signálem regulované MAP kinasy fyziologie MeSH
- indican * fyziologie škodlivé účinky MeSH
- lipoproteiny LDL fyziologie MeSH
- makrofágy fyziologie MeSH
- MAP kinasový signální systém fyziologie účinky léků MeSH
- nádorové buněčné linie fyziologie MeSH
- průtoková cytometrie MeSH
- techniky in vitro MeSH
- viabilita buněk účinky léků MeSH
- Publikační typ
- práce podpořená grantem MeSH
Urine contains a variety of organic and inorganic chemicals including a number of natural fluorophores. Most of them are formed by tryptophan metabolites. But there are also metabolites of riboflavin, catecholamines and porphyrins. The alternation in the autofluorescence of urine and the alternation in the concentration of these substances are developed by both physiological and pathological changes such as disorder of body metabolism, dietary intake, age and etc. In this work we present fluorescent properties of chosen urine fluorophores – i.e. 5-hydroxyindole-3-acetic acid (5-HIAA), indoxyl sulphate (urine indican), serotonin (5-HT), vanillylmandelic (VMA) and homovanillic (HVA) acids typical for various diseases. Differences of fluorescent parameters of individual fluorophores measured in vitro in the water solutions and in natural environment of urine are significant and can lead to false results and conclusions. Therefore, we present the most common influence that can occur in urine (e.g. pH, ionic strength, proteins, and other fluorophores). The aim is to elaborate the exact “know-how” for direct complex fluorescent measurement in urine related to particular diagnoses.
