316 research outputs found

    The intestine and the kidneys : a bad marriage can be hazardous

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    The concept that the intestine and chronic kidney disease influence each other, emerged only recently. The problem is multifaceted and bidirectional. On one hand, the composition of the intestinal microbiota impacts uraemic retention solute production, resulting in the generation of essentially protein-bound uraemic toxins with strong biological impact such as vascular damage and progression of kidney failure. On the other hand, the uraemic status affects the composition of intestinal microbiota, the generation of uraemic retention solutes and their precursors and causes disturbances in the protective epithelial barrier of the intestine and the translocation of intestinal microbiota into the body. All these elements together contribute to the disruption of the metabolic equilibrium and homeostasis typical to uraemia. Several measures with putative impact on intestinal status have recently been tested for their influence on the generation or concentration of uraemic toxins. These include dietary measures, prebiotics, probiotics, synbiotics and intestinal sorbents. Unfortunately, the quality and the evidence base of many of these studies are debatable, especially in uraemia, and often results within one study or among studies are contradictory. Nevertheless, intestinal uraemic metabolite generation remains an interesting target to obtain in the future as an alternative or additive to dialysis to decrease uraemic toxin generation. In the present review, we aim to summarize (i) the role of the intestine in uraemia by producing uraemic toxins and by generating pathophysiologically relevant changes, (ii) the role of uraemia in modifying intestinal physiology and (iii) the therapeutic options that could help to modify these effects and the studies that have assessed the impact of these therapies

    Uraemic toxins and new methods to control their accumulation : game changers for the concept of dialysis adequacy

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    The current concept of an adequate dialysis based only on the dialysis process itself is rather limited. We now have considerable knowledge of uraemic toxicity and improved tools for limiting uraemic toxin accumulation. It is time to make use of these. A broader concept of adequacy that focusses on uraemic toxicity is required. As discussed in the present review, adequacy could be achieved by many different methods in combination with, or instead of, dialysis. These include preservation of renal function, dietary intake, reducing uraemic toxin generation rate and intestinal absorption, isolated ultrafiltration and extracorporeal adsorption of key uraemic toxins. A better measure of the quality of dialysis treatment would quantify the uraemic state in the patient using levels of a panel of key uraemic toxins. Treatment would focus on controlling uraemic toxicity while reducing harm or inconvenience to the patient. Delivering more dialysis might not be the best way to achieve this

    Comparison of five assays for DNA extraction from bacterial cells in human faecal samples

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    Aim To determine the most effective DNA extraction method for bacteria in faecal samples. Materials and Results This study assessed five commercial methods, that is, NucliSens easyMag, QIAamp DNA Stool Mini kit, PureLink Microbiome DNA purification kit, QIAamp PowerFecal DNA kit and RNeasy PowerMicrobiome kit, of which the latter has been optimized for DNA extraction. The DNA quantity and quality were determined using Nanodrop, Qubit and qPCR. The PowerMicrobiome kit recovered the highest DNA concentration, whereby this kit also recovered the highest gene copy number of Gram positives, Gram negatives and total bacteria. Furthermore, the PowerMicrobiome kit in combination with mechanical pre-treatment (bead beating) and with combined enzymatic and mechanical pre-treatment (proteinase K+mutanolysin+bead beating) was more effective than without pre-treatment. Conclusion From the five DNA extraction methods that were compared, the PowerMicrobiome kit, preceded by bead beating, which is standard included, was found to be the most effective DNA extraction method for bacteria in faecal samples. Significance and Impact of the Study The quantity and quality of DNA extracted from human faecal samples is a first important step to optimize molecular methods. Here we have shown that the PowerMicrobiome kit is an effective DNA extraction method for bacterial cells in faecal samples for downstream qPCR purpose

    p-Cresyl sulfate

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    If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden

    Gut-derived metabolites and their role in immune dysfunction in chronic kidney disease

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    Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H2S affect the intestinal barrier structure and function while in the circulation the related uremic toxins stimulate cells of the immune system. Both conditions contribute to the pro-inflammatory status of patients with chronic kidney disease (CKD). Generation and/or absorption of these toxin precursors could be targeted to decrease plasma levels of their respective uremic toxins and to reduce micro-inflammation in CKD

    Looking beyond endotoxin: a comparative study of pyrogen retention by ultrafilters used for the preparation of sterile dialyis fluid

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    Sterile single-use ultrafilters are used in dialysis for the preparation of the substitution fluid given to patients undergoing dialysis treatments with high convective fluid removal. The retention of pyrogenic agents by the ultrafilters is crucial to avoiding inflammatory responses. The performance of a new single-use ultrafilter (NUF) with a positively charged flat sheet membrane of relatively small membrane area and large pore size was compared to a reference ultrafilter (RUF) with a hollow fiber membrane. Filter performance was tested with various pyrogen-contaminated dialysis fluids by direct pyrogen quantification and by measuring inflammatory responses in cell-based bioassays. The NUF completely retained oligodeoxynucleotides (ODN), whereas the RUF was fully permeable. Both filters tended to decrease biological activity of DNA in filtered bacterial lysates. The NUF reduced lipopolysaccharides (LPS) and LPS-induced biological activity by 100%, whereas the RUF produced filtrates with low but detectable levels of LPS in most cases. Peptidoglycans (PGN) were fully retained both by the NUF and the RUF. The new ultrafilter retained biologically active ODN, which has not yet been described for any other device used in dialysis, and it showed better or equal retention of LPS and PGN even with a smaller membrane surface and larger pore size

    Where and when to inject low molecular weight heparin in hemodiafiltration? : a cross over randomised trial

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    Background and Objective : Low molecular weight heparins (LMWHs) are small enough to pass large pore dialysis membranes. Removal of LMWH if injected before the start of the session is possible during high-flux dialysis and hemodiafiltration. The aim of this study was to determine the optimal mode (place and time) of tinzaparin administration during postdilution hemodiafiltration. Study Design, Setting, Patients : In 13 chronic hemodiafiltration patients, 3 approaches of injection were compared in a randomised cross over trial: i) before the start of the session at the inlet blood line filled with rinsing solution (IN0), ii) 5 min after the start at the inlet line filled with blood (IN5) and iii) before the start of the session at the outlet blood line (OUT0). Anti-Xa activity, thrombin generation, visual clotting score and reduction ratios of urea and beta2microglobulin were measured. Results : Anti-Xa activity was lower with IN0 compared with IN5 and OUT0, and also more thrombin generation was observed with IN0. No differences were observed in visual clotting scores and no clinically relevant differences were observed in solute reduction ratio. An anti-Xa of 0.3 IU/mL was discriminative for thrombin generation. Anti-Xa levels below 0.3 IU/mL at the end of the session were associated with worse clotting scores and lower reduction ratio of urea and beta2microglobulin. Conclusions : Injection of tinzaparin at the inlet line before the start of postdilution hemodiafiltration is associated with loss of anticoagulant activity and can therefore not be recommended. Additionally, we found that an anti-Xa above 0.3 IU/mL at the end of the session is associated with less clotting and higher dialysis adequacy
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