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Uremic toxins

Qiong Wu, Huan Zhang, Jia-Rong Ding, Zhan-Ying Hong, Hao Wu, Zhen-Yu Zhu, Zhi-Yong Guo, Yi-Feng Chai
As one of the most troublesome complications in patients with chronic renal disease, the etiology of uremic pruritus remains unknown, and the current therapeutic approaches are limited and unsatisfactory. To identify potential biomarkers for improving diagnosis and treatment and obtain a better understanding of the pathogenesis of uremic pruritus, we compared serum metabolome profiles of severe uremic pruritus (HUP) patients with mild uremic pruritus (LUP) patients using ultraperformance liquid chromatography-quadruple time-of-flight mass spectrometry (UPLC-QTOF MS)...
2018: BioMed Research International
Yong Li, Peggy Sekula, Matthias Wuttke, Judith Wahrheit, Birgit Hausknecht, Ulla T Schultheiss, Wolfram Gronwald, Pascal Schlosser, Sara Tucci, Arif B Ekici, Ute Spiekerkoetter, Florian Kronenberg, Kai-Uwe Eckardt, Peter J Oefner, Anna Köttgen
Background The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions. Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD. Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios...
March 15, 2018: Journal of the American Society of Nephrology: JASN
Takuya Wakamatsu, Suguru Yamamoto, Toru Ito, Yoko Sato, Koji Matsuo, Yoshimitsu Takahashi, Yoshikatsu Kaneko, Shin Goto, Junichiro James Kazama, Fumitake Gejyo, Ichiei Narita
In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay...
March 15, 2018: Toxins
James Gilbert Atherton, David S Hains, John J Bissler, Bradford D Pendley, Erno Lindner
Current dialysis dosing calculations provide an incomplete assessment of blood purification. They do not include clearances of protein-bound uremic toxins like polyamines, p-cresol sulfate, and indoxyl sulfate, relying solely on the clearance of urea as a surrogate for all molecules accumulating in patients with end stage renal disease (ESRD). Protein-bound uremic toxins clear differently in dialysis but also during normal renal function. The kidney clears protein bound toxins via the process of secretion, while it clears urea through filtration...
March 14, 2018: American Journal of Physiology. Renal Physiology
Kinnosuke Yahiro, Sayaka Nagasawa, Kimitoshi Ichimura, Hiroki Takeuchi, Kohei Ogura, Hiroyasu Tsutsuki, Takeshi Shimizu, Sunao Iyoda, Makoto Ohnishi, Hirotaro Iwase, Joel Moss, Masatoshi Noda
Shiga toxigenic Escherichia coli (STEC) are responsible for a worldwide foodborne disease, which is characterized by severe bloody diarrhea and hemolytic uremic syndrome (HUS). Subtilase cytotoxin (SubAB) is a novel AB5 toxin, which is produced by Locus for Enterocyte Effacement (LEE)-negative STEC. Cleavage of the BiP protein by SubAB induces endoplasmic reticulum (ER) stress, followed by induction of cytotoxicity in vitro or lethal severe hemorrhagic inflammation in mice. Here we found that steroids and diacylglycerol (DAG) analogues (e...
December 2018: Cell Death Discovery
Wei Ling Lau, Javad Savoj, Michael B Nakata, Nosratola D Vaziri
In chronic kidney disease (CKD), influx of urea and other retained toxins exerts a change in the gut microbiome. There is decreased number of beneficial bacteria that produce short-chain fatty acids, an essential nutrient for the colonic epithelium, concurrent with an increase in bacteria that produce uremic toxins such as indoxyl sulphate, p -cresyl sulphate, and trimethylamine-N-oxide (TMAO). Due to intestinal wall inflammation and degradation of intercellular tight junctions, gut-derived uremic toxins translocate into the bloodstream and exert systemic effects...
March 15, 2018: Clinical Science (1979-)
Bin Yang, Shaomeng Wang, Jianxiao Huang, Zhiqiu Yin, Lingyan Jiang, Wenqi Hou, Xiaomin Li, Lu Feng
Enterohemorrhagic Escherichia coli O157:H7 is a major human enteric pathogen capable of causing large outbreaks of severe infections that induce bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Its genome contains 177 unique O islands (OIs) including those carrying the main virulence elements, Shiga toxin-converting phages (OI-45 and OI-93) and locus for enterocyte effacement (OI-148). However, many of these islands harbor only genes of unknown function. Here, we demonstrate that OI-29 encodes a newly discovered transcriptional activator, Z0639 (named GmrA), that is required for motility and flagellar synthesis in O157:H7...
2018: Frontiers in Microbiology
Chisa Fukasawa, Saori Ooishi, Takuma Kumagai, Megumi Koshiisi, Yuki Sueki, Kei Nakajima, Toru Mitsumori, Yoko Yoshida, Hideki Kato, Masaomi Nangaku, Toshiyuki Miyata, Keita Kirito
Herein, we present an elderly onset case of aHUS successfully treated with eculizumab. An 80-year-old woman with severe anemia, thrombocytopenia, and acute renal dysfunction was admitted to our hospital. A laboratory test revealed steep elevation in the LDH level, and the peripheral blood smear showed erythrocyte fragmentations. Accordingly, we diagnosed thrombotic microangiopathy, and treatment with plasma exchange was immediately initiated. In addition, she required hemodialysis because of rapid impairment of the renal function...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Christian Patry, Christian Betzen, Farnoosh Fathalizadeh, Alexander Fichtner, Jens H Westhoff, Thomas Fleming, Volker Eckstein, Tom Bruckner, Martina Bielaszewska, Helge Karch, Georg F Hoffmann, Burkhard Tönshoff, Neysan Rafat
Endothelial injury with consecutive microangiopathy and endothelial dysfunction plays a central role in the pathogenesis of the post-enteropathic hemolytic uremic syndrome (D+HUS). To identify new treatment strategies, we examined the regenerative potential of endothelial progenitor cells (EPC) in an in vitro model of Shiga toxin (Stx) 2a-induced glomerular endothelial injury present in D+HUS and the mechanisms of EPC-triggered endothelial regeneration. We simulated the pro-inflammatory milieu present in D+HUS by priming human renal glomerular endothelial cells (HRGEC) with Tumor Necrosis Factor (TNF)-α prior to stimulation with Stx2a...
March 7, 2018: American Journal of Physiology. Renal Physiology
Shuo Niu, John Paluszynski, Zhen Bian, Lei Shi, Koby Kidder, Yuan Liu
Shiga toxin (Stx)-induced hemolytic uremic syndrome (HUS) is a life-threatening complication associated with Stx-producing Escherichia coli infection. One critical barrier of understanding HUS is how Stx transports from infected intestine to kidney to cause HUS. Passive dissemination seems unlikely, while circulating blood cells have been debated to serve as the toxin carrier. Employing a murine model of Stx2-induced HUS with LPS priming (LPS-Stx2), we investigate how Stx causes HUS and identify possible toxin carrier...
March 5, 2018: Scientific Reports
Martin Wolley, Meg Jardine, Colin A Hutchison
Dialysis technologies have continued to advance over recent decades; however, these advancements have not always been met with improved patient outcomes. In part, the high morbidity and mortality associated with dialysis have been attributed to a group of uremic toxins, which are described as "difficult to remove." With a new generation of hemodialysis membranes now making meaningful clearance of these molecules possible, it is an apt time to review the clinical relevance of these middle molecules...
March 5, 2018: Clinical Journal of the American Society of Nephrology: CJASN
J D Tanaro, L A Pianciola, B A D'Astek, M C Piaggio, M L Mazzeo, G Zolezzi, M Rivas
Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a worldwide concern. Cattle are their main reservoir and may contaminate watercourses through manure. We characterized a collection of 38 STEC O157:H7 strains isolated from surface water in feedlots areas (puddles inside pens formed after the rainfall or by spill around drinking troughs, and small water courses and lagoons, formed by runoff). Nineteen (50.0%) strains harbored stx2a /stx2c genes, 18 (47.4%) stx2c and one stx1a /stx2c . All strains harbored eae, ehxA, rfbO157 , and fliCH 7 genes, and the putative virulence determinants ECSP_0242, ECSP_2687 and ECSP_3620...
March 3, 2018: Letters in Applied Microbiology
Evelien Snauwaert, Wim Van Biesen, Ann Raes, Griet Glorieux, Raymond Vanholder, Johan Vande Walle, Sunny Eloot
No abstract text is available yet for this article.
March 2, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Robert Alvin Bernedo-Navarro, Ema Romão, Tomomasa Yano, Joar Pinto, Henri De Greve, Yann G-J Sterckx, Serge Muyldermans
BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) are a subset of pathogens leading to illnesses such as diarrhea, hemolytic uremic syndrome and even death. The Shiga toxins are the main virulence factors and divided in two groups: Stx1 and Stx2, of which the latter is more frequently associated with severe pathologies in humans. RESULTS: An immune library of nanobodies (Nbs) was constructed after immunizing an alpaca with recombinant Shiga toxin-2a B subunit (rStx2aB), to retrieve multiple rStx2aB-specific Nbs...
March 1, 2018: Toxins
Ke Wang, Bryan Kestenbaum
The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane...
February 28, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Violeta Cazaña-Pérez, Pilar Cidad, Javier Donate-Correa, Ernesto Martín-Núñez, José R López-López, M Teresa Pérez-García, Teresa Giraldez, Juan F Navarro-González, Diego Alvarez de la Rosa
Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular disease (CVD). The high concentration of circulating uremic toxins and alterations in mineral metabolism and hormone levels produce vascular wall remodeling and significant vascular damage. Medial calcification is an early vascular event in CKD patients and is associated to apoptosis or necrosis and trans-differentiation of vascular smooth muscle cells (VSMC) to an osteogenic phenotype. VSMC obtained from bovine or rat aorta and cultured in the presence of increased inorganic phosphate (Pi) have been extensively used to study these processes...
2018: Frontiers in Physiology
Jun Lai, Gael Akindavyi, Qiang Fu, Zhi-Liang Li, Hui-Min Wang, Li-Hua Wen
Objective: Coronary artery calcification (CAC) is thought to be a controlled metabolic process that is very similar to the formation of new bone. In patients with chronic renal failure (CRF), CAC is very common, and CAC severity correlates with the deterioration of renal function. We summarized the current understanding and emerging findings of the relationship between CAC and CRF. Data Sources: All studies were identified by systematically searching PubMed, Embase, and CNKI databases for the terms "coronary calcification", "chronic renal failure", "vascular smooth muscle cell", and their synonyms until September 2017...
March 5, 2018: Chinese Medical Journal
Adriana Albanese, Flavia Sacerdoti, E Abril Seyahian, Maria Marta Amaral, Gabriela Fiorentino, Romina Fernandez Brando, Daniel A Vilte, Elsa C Mercado, Marina S Palermo, Angel Cataldi, Elsa Zotta, Cristina Ibarra
E. coli O157:H7 is a foodborne pathogen responsible for bloody diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS). The objective of the present work was to evaluate the ability of colostral IgG obtained from Stx2-immunized cows to prevent against E. coli O157:H7 infection and Stx2 cytotoxicity. Hyperimmune colostrum (HC) was obtained from cows intramuscularly immunized with inactivated Stx2 or vehicle for controls. Colostral IgG was purified by affinity chromatography. Specific IgG antibodies against Stx2 and bovine lactoferrin (bLF) levels in HC and the corresponding IgG (HC-IgG/bLF) were determined by ELISA...
February 23, 2018: Vaccine
Victor Ntuli, Patrick M K Njage, Paolo Bonilauri, Andrea Serraino, Elna M Buys
This study was conducted to estimate the hemolytic uremic syndrome (HUS) risk associated with consumption of producer-distributor bulk milk (PDBM) contaminated with Shiga toxin-producing Escherichia coli (STEC) in South Africa. Data were obtained from recently completed studies in South Africa taking into account prior collected prevalence data of STEC in raw and pasteurized PDBM and survey information from producer-distributor outlets and households. Inputs for the models were complemented with data from published and unpublished literature...
February 23, 2018: Journal of Food Protection
Arlène Ghajarzadeh-Wurzner, Maxime Berney, Daniel Teta, Laurence Genton, Menno Pruijm
Recent studies have found a relationship between the kidney and the intestinal microbiome, called the colo-renal axis. Mounting evidence suggests that patients suffering from chronic kidney disease (CKD) have an altered composition of gut microbiota. This leads to 1) the increased fermentation of intestinal proteins to uremic toxins such as p-cresyl sulphate and indoxyl sulphate, 2) an altered, more 'leaky' intestinal barrier, and 3) translocation of bacteria and toxins from the gut lumen to the circulation, inducing systemic inflammation...
February 21, 2018: Revue Médicale Suisse
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