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Uremic toxins

Valentina Talarico, Monica Aloe, Alice Monzani, Roberto Miniero, Gianni Bona
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption...
December 2016: Minerva Pediatrica
James Tattersall
Current guidelines focus on conventional dialysis defined as 3-5 hours, three times per week, and suggest that longer or more frequent dialysis be considered. This paper presents the case for considering that shorter or less frequent dialysis should also be considered. More frequent and/or longer dialysis facilitates control of fluid overload, blood pressure, and phosphate levels. These benefits will require time to translate into probable hard outcome improvement. Patients are unlikely to participate in productive or pleasurable activities while undergoing dialysis in center or traveling to treatment...
October 20, 2016: Seminars in Dialysis
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belén Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Kunal K Sindhu
Chronic kidney disease (CKD) is characterized by the progressive reduction of glomerular filtration rate and subsequent retention of organic waste compounds called uremic toxins. While patients with CKD are at a higher risk of premature death due to cardiovascular complications, this increased risk cannot be completely explained by classical cardiovascular risk factors such as hypertension, diabetes mellitus, and obesity. Instead, recent research suggests that uremic toxins may play a key role in explaining this marked increase in cardiovascular mortality in patients with CKD...
October 19, 2016: Renal Failure
Natália A Borges, Amanda F Barros, Lia S Nakao, Carla J Dolenga, Denis Fouque, Denise Mafra
OBJECTIVE: Protein-bound uremic toxins from gut microbiota tend to accumulate in chronic kidney disease (CKD) patients and are poorly removed by current dialysis techniques. These toxins induce inflammation and are associated with cardiovascular disease (CVD). The aim of this study was to report the relationship between uremic toxins and inflammatory and cardiovascular markers in CKD patients. DESIGN: This was a cross sectional study. SUBJECTS: Twenty-one nondialysis patients were included (43% men, 63...
November 2016: Journal of Renal Nutrition
Suman Pradhan, Christine Pellino, Kayleigh MacMaster, Dennis Coyle, Alison A Weiss
Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli, and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed...
2016: Frontiers in Cellular and Infection Microbiology
Stephen B Freedman, Mohamed Eltorki, Linda Chui, Jianling Xie, Sharon Feng, Judy MacDonald, Andrew Dixon, Samina Ali, Marie Louie, Bonita E Lee, Lara Osterreicher, Jennifer Thull-Freedman
OBJECTIVE: To identify the gaps in the care of children infected with Shiga toxin-producing Escherichia coli (STEC), we sought to quantitate care received and management timelines. Such knowledge is crucial to the design of interventions to prevent the development of hemolytic uremic syndrome (HUS). STUDY DESIGN: We conducted a retrospective case-series study of 78 children infected with STEC in Alberta, Canada, through the linkage of microbiology and laboratory results, telephone health advice records, hospital charts, physician billing submissions, and outpatient antimicrobial dispensing databases...
October 10, 2016: Journal of Pediatrics
Ingrid Palma-Martínez, Andrea Guerrero-Mandujano, Manuel J Ruiz-Ruiz, Cecilia Hernández-Cortez, José Molina-López, Virgilio Bocanegra-García, Graciela Castro-Escarpulli
Shiga-like toxins (Stx) represent a group of bacterial toxins involved in human and animal diseases. Stx is produced by enterohemorrhagic Escherichia coli, Shigella dysenteriae type 1, Citrobacter freundii, and Aeromonas spp.; Stx is an important cause of bloody diarrhea and hemolytic uremic syndrome (HUS). The aim of this study was to identify the stx1/stx2 genes in clinical strains and outer membrane vesicles (OMVs) of Aeromonas spp., 66 strains were isolated from children who live in Mexico City, and Stx effects were evaluated in Vero cell cultures...
2016: Frontiers in Microbiology
Dineke Westra, Elena B Volokhina, Renate G van der Molen, Thea J A M van der Velden, Annelies Jeronimus-Klaasen, Joop Goertz, Valentina Gracchi, Eiske M Dorresteijn, Antonia H M Bouts, Mandy G Keijzer-Veen, Joanna A E van Wijk, Jaap A Bakker, Anja Roos, Lambert P van den Heuvel, Nicole C A J van de Kar
BACKGROUND: The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS. METHODS: Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS...
October 7, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Krzysztof Mikołajczyk, Radosław Kaczmarek, Marcin Czerwiński
Transcription factor EKLF (Erythroid Krüppel-Like Factor) belongs to the group of Krüppellike factors, which regulate proliferation, differentiation, development and apoptosis of mammalian cells. EKLF factor is present in erythroid cells, where it participates in regulation of hematopoiesis, expression of genes encoding transmembrane proteins (including blood group antigens), and heme biosynthesis enzymes. It is also a key factor in downregulation of γ-globins and activation of β-globin gene expression...
October 6, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Denys Pavlenko, Esmée van Geffen, Mies J van Steenbergen, Griet Glorieux, Raymond Vanholder, Karin G F Gerritsen, Dimitrios Stamatialis
Hemodialysis is a widely available and well-established treatment for patients with End Stage Renal Disease (ESRD). However, although life-sustaining, patient mortality rates are very high. Several recent studies corroborated the link between dialysis patients' outcomes and elevated levels of protein-bound uremic toxins (PBUT) that are poorly removed by conventional hemodialysis. Therefore, new treatments are needed to improve their removal. Recently, our group showed that the combination of dialysis and adsorption on one membrane, the mixed matrix membrane (MMM), can effectively remove those toxins from human plasma...
October 5, 2016: Scientific Reports
Mami Kikuchi, Mariko Ueno, Yoshiharu Itoh, Wataru Suda, Masahira Hattori
BACKGROUND: In patients with chronic kidney disease (CKD), many metabolites of gut microbiota retain in the body as uremic toxins (UTs). However, the kinds of bacteria producing UTs are rarely discussed. METHODS: We analyzed UT production and the composition of gut microbiota in CKD rats and cecectomized rats. AST-120, a spherical carbon adsorbent, was administrated to evaluate how the precursors of UT affect gut microbiota. Serum and urine levels of UTs were quantified by liquid chromatography/electrospray ionization-tandem mass spectrometry...
October 5, 2016: Nephron
Akitomo Shibata, Yu Ishima, Mayumi Ikeda, Hirokazu Sato, Tadashi Imafuku, Victor T G Chuang, Yuya Ouchi, Takaya Abe, Hiroshi Watanabe, Tatsuhiro Ishida, Masaki Otagiri, Toru Maruyama
Recently, hydropersulfide (RSSH) was found to exist in mammalian tissues and fluids. Cysteine hydropersulfide can be found in free cysteine residues as well as in proteins, and it has potent antioxidative activity. Human serum albumin (HSA) is the most abundant protein in mammalian serum. HSA possesses a free thiol group in Cys-34 that could be a site for hydropersulfide formation. HSA hydropersulfide of high purity as a positive control was prepared by treatment of HSA with Na2S. The presence of HSA hydropersulfide was confirmed by spectroscopy and ESI-TOFMS analysis where molecular weights of HSA hydropersulfide by increments of approximately 32 Da (Sulfur atom) were detected...
October 21, 2016: Biochemical and Biophysical Research Communications
Dorota Wirkus, Aleksandra Jakubus, Radosław Owczuk, Piotr Stepnowski, Monika Paszkiewicz
Continous renal replacement therapy (CRRT) is particularly recommended for septic shock patients in intensive care units. The CRRT technique used most frequently is high volume continuous veno-venous haemofiltration. It provides a high rate of clearance of uremic toxins and inflammatory cytokines. However, it should also be taken into account that substances important for homeostasis may be concurrently unintentionally removed. Accordingly, water-soluble vitamins can be removed during continuous renal replacement therapy, and the estimate of the loss is critical to ensure appropriate supplementation...
September 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Janice Crespo-Salgado, V Matti Vehaskari, Tyrus Stewart, Michael Ferris, Qiang Zhang, Guangdi Wang, Eugene E Blanchard, Christopher M Taylor, Mahmoud Kallash, Larry A Greenbaum, Diego H Aviles
BACKGROUND: End-stage renal disease (ESRD) is associated with uremia and increased systemic inflammation. Alteration of the intestinal microbiota may facilitate translocation of endotoxins into the systemic circulation leading to inflammation. We hypothesized that children with ESRD have an altered intestinal microbiota and increased serum levels of bacterially derived uremic toxins. METHODS: Four groups of subjects were recruited: peritoneal dialysis (PD), hemodialysis (HD), post-kidney transplant and healthy controls...
2016: Microbiome
Diana Karpman, Ramesh Tati
Complement is activated during Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS). There is evidence of complement activation via the alternative pathway in STEC-HUS patients as well as from in vivo and in vitro models. Ozaki et al. demonstrate activation of the mannose-binding lectin (MBL) pathway in Shiga toxin-treated mice expressing human MBL2, but lacking murine Mbls. Treatment with anti-human MBL2 antibody was protective, suggesting that MBL pathway activation also contributes to Shiga toxin-mediated renal injury...
October 2016: Kidney International
Fatemeh Saheb Sharif-Askari, Syed Azhar Syed Sulaiman, Narjes Saheb Sharif-Askari
Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding...
September 15, 2016: Advances in Experimental Medicine and Biology
Daniel Tapia, Brittany N Ross, Anjana Kalita, Mridul Kalita, Christopher L Hatcher, Laura A Muruato, Alfredo G Torres
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a leading cause of foodborne illnesses worldwide and is a common serotype linked to hemorrhagic colitis and an important cause of hemolytic uremic syndrome (HUS). Treatment of EHEC O157:H7 infections is complicated, as antibiotics can exacerbate Shiga toxin (Stx) production and lead to more severe symptoms including HUS. To date, no vaccines have been approved for human use, exposing a void in both treatment and prevention of EHEC O157:H7 infections. Previously, our lab has shown success in identifying novel vaccine candidates via bio- and immunoinformatics approaches, which are capable of reducing bacterial colonization in an in vivo model of intestinal colonization...
2016: Frontiers in Cellular and Infection Microbiology
Jimena S Cadona, Ana V Bustamante, Juliana González, A Mariel Sanso
Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen responsible for severe disease in humans such as hemolytic uremic syndrome (HUS) and cattle, the principal reservoir. Identification of the clones/lineages is important as several characteristics, among them propensity to cause disease varies with STEC phylogenetic origin. At present, we do not know what STEC clones, especially of non-O157:H7, are circulating in Argentina. To fill this knowledge gap we assessed the genetic diversity of STEC strains isolated in Argentina from various sources, mostly cattle and food, using multilocus sequence typing (MLST)...
2016: Frontiers in Cellular and Infection Microbiology
Armando Navarro, Ulises Hernández-Chiñas, Delia Licona-Moreno, Edgar Zenteno, Alejandro Cravioto, Carlos A Eslava-Campos
Escherichia coli O157:H7 is a subtype of Shiga toxin-producing E. coli (STEC) that is associated with haemorrhagic colitis and haemolytic uremic syndrome (HUS). Studies of populations in endemic areas have reported that the presence of specific antibodies against the O157 lipopolysaccharide (LPS) is associated with a lower incidence of diarrhoea and HUS. Phage display and IgG anti-O157 LPS antibodies were used in this study to select peptide mimotopes of O157 LPS expressed in protein III of the M13 phage. Synthetic peptides (SP) were designed using the derived amino acid sequences obtained from DNA nucleotides of 63 selected phagotopes...
September 13, 2016: Biochemical Journal
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