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Uremic toxins

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https://www.readbyqxmd.com/read/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#1
Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya-Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y Yang, Xin Wang, Eric T Choi, Rongshan Li, Hong Wang, Xiao-Feng Yang
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80(th) of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28930030/mild-illness-during-outbreak-of-shiga-toxin-producing-escherichia-coli-o157-infections-associated-with-agricultural-show-australia
#2
Bhakti R Vasant, Russell J Stafford, Amy V Jennison, Sonya M Bennett, Robert J Bell, Christine J Doyle, Jeannette R Young, Susan A Vlack, Paul Titmus, Debra El Saadi, Kari A J Jarvinen, Patricia Coward, Janine Barrett, Megan Staples, Rikki M A Graham, Helen V Smith, Stephen B Lambert
During a large outbreak of Shiga toxin-producing Escherichia coli illness associated with an agricultural show in Australia, we used whole-genome sequencing to detect an IS1203v insertion in the Shiga toxin 2c subunit A gene of Shiga toxin-producing E. coli. Our study showed that clinical illness was mild, and hemolytic uremic syndrome was not detected.
October 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28928007/removal-of-uremic-retention-products-by-hemodialysis-is-coupled-with-indiscriminate-loss-of-vital-metabolites
#3
Zhi-Hao Zhang, Jia-Rong Mao, Hua Chen, Wei Su, Yuan Zhang, Li Zhang, Dan-Qian Chen, Ying-Yong Zhao, Nosratola D Vaziri
BACKGROUND: Although dialysis ameliorates uremia and fluid and electrolytes disorders, annual mortality rate remains high in dialysis population reflecting its shortcoming in replacing renal function. Unlike the normal kidney, dialysis causes dramatic shifts in volume and composition of body fluids and indiscriminate removal of vital solutes. Present study was undertaken to determine the impact of hemodialysis on plasma metabolites in end-stage renal disease (ESRD) patients. METHODS: 80 hemodialysed patients and 80 age/gender-matched healthy controls were enrolled in the study...
September 16, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28925976/shiga-toxin-therapeutics-beyond-neutralization
#4
REVIEW
Gregory Hall, Shinichiro Kurosawa, Deborah J Stearns-Kurosawa
Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells...
September 19, 2017: Toxins
https://www.readbyqxmd.com/read/28925349/real-time-genomic-investigation-underlying-the-public-health-response-to-a-shiga-toxin-producing-escherichia-coli-o26-h11-outbreak-in-a-nursery
#5
J Moran-Gilad, A Rokney, D Danino, M Ferdous, F Alsana, M Baum, L Dukhan, V Agmon, E Anuka, L Valinsky, R Yishay, I Grotto, J W A Rossen, M Gdalevich
Shiga toxin-producing Escherichia coli (STEC) is a significant cause of gastrointestinal infection and the haemolytic-uremic syndrome (HUS). STEC outbreaks are commonly associated with food but animal contact is increasingly being implicated in its transmission. We report an outbreak of STEC affecting young infants at a nursery in a rural community (three HUS cases, one definite case, one probable case, three possible cases and five carriers, based on the combination of clinical, epidemiological and laboratory data) identified using culture-based and molecular techniques...
September 19, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28922657/methods-employed-in-cytofluorometric-assessment-of-eryptosis-the-suicidal-erythrocyte-death
#6
Mohamed Jemaà, Myriam Fezai, Rosi Bissinger, Florian Lang
Suicidal erythrocyte death or eryptosis contributes to or even accounts for anemia in a wide variety of clinical conditions, such as iron deficiency, dehydration, hyperphosphatemia, vitamin D excess, chronic kidney disease (CKD), hemolytic-uremic syndrome, diabetes, hepatic failure, malignancy, arteriitis, sepsis, fever, malaria, sickle-cell disease, beta-thalassemia, Hb-C and G6PD-deficiency, Wilsons disease, as well as advanced age. Moreover, eryptosis is triggered by a myriad of xenobiotics and endogenous substances including cytotoxic drugs and uremic toxins...
September 1, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28918555/prognostic-factors-for-mortality-in-middle-aged-and-older-hemodialysis-patients-a-5-year-observational-study
#7
Kojiro Nagai, Motokazu Matsuura, Kenji Tsuchida, Hiro-Omi Kanayama, Toshio Doi, Jun Minakuchi
Clinical guidelines for hemodialysis therapy have been described in an evidence-based manner with most evidence from randomized control trials or retrospective studies in which all generations of the hemodialysis patients were enrolled. Therefore, the question still remains whether these guidelines can be applied to increasing older patients. This study is an observational study, including 735 patients who received maintenance hemodialysis in April 2006. At baseline, the participants' age was 62.1 ± 12...
September 16, 2017: Journal of Artificial Organs: the Official Journal of the Japanese Society for Artificial Organs
https://www.readbyqxmd.com/read/28910801/large-middle-molecule-and-albumin-removal-why-should-we-not-rest-on-our-laurels
#8
Nans Florens, L Juillard
Large middle molecules (LMM) are an important subclass of uremic toxins. Many of them have been linked with poor outcomes in hemodialysis (HD) patients. The onset of high-flux membranes and convective techniques allowed to dramatically improve their clearance but without a clear and undebatable reduction of mortality in HD patients. Despite the real effect on the removal of selected toxins, little is known about the influence of modern HD techniques on the global removal of uremic toxins. Mostly explained by a lack of knowledge and selective assays, LMM removal is not evaluated appropriately...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910800/the-place-of-large-pore-membranes-in-the-treatment-portfolio-of-patients-on-hemodialysis
#9
Wim Van Biesen, Raymond Vanholder, Eva Schepers, Griet Glorieux, Annemieke Dhondt, Sunny Eloot
Cardiovascular disease is a major concern in patients with end-stage kidney disease (ESKD). Inflammation induced by retention of uremic toxins, of which a substantial fraction has a molecular weight in the middle molecular range, has been associated with increased cardiovascular risk. In an attempt to reduce inflammation and thus cardiovascular toxicity in patients with ESKD, hemodiafiltration (HDF) has been promoted to enhance the clearance of middle molecular weight substances during dialysis. However, HDF increases the technical complexity and costs, and requires ultrapure dialysis fluid...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910799/effects-of-hemodialysis-therapy-using-dialyzers-with-medium-cut-off-membranes-on-middle-molecules
#10
Alexander H Kirsch, Alexander R Rosenkranz, Raphael Lyko, Detlef H Krieter
The removal of larger middle molecules, such as free immunoglobulin light chains (FLC), is poor with most currently used dialysis technologies. While hemodiafiltration (HDF) provides enhanced clearance of middle molecules compared to high-flux hemodialysis (HD), this technique is currently not approved in some regions and, hence, not accessible for all patients. The retention of middle molecules is thought to be one factor, which contributes to excessive morbidity and mortality in HD patients. The development of medium cut-off (MCO) dialysis membranes is aimed at a more efficient clearance of larger uremic toxins while retaining albumin and may extend the benefit of enhanced solute removal to more patients...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910797/the-rationale-for-expanded-hemodialysis-therapy-hdx
#11
Colin A Hutchison, Martin Wolley
As dialysis membrane technologies have advanced, the ability to clear increasing numbers of uremic toxins has occurred. To date, however, the class of uremic toxins known as large middle-molecules has been classified as "difficult to remove." Expanded hemodialysis utilizes a new generation of high-retention-onset hemodialysis membranes; these membranes provide the ability to remove large middle-molecules effectively for the first time, without significant albumin loss. In this review, we evaluate the removal of large middle-molecules by the new high-retention-onset membranes, the clinical relevance of these molecules, and how expanded hemodialysis can be prescribed...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910796/modeling-of-internal-filtration-in-theranova-hemodialyzers
#12
Anna Lorenzin, Mauro Neri, William R Clark, Francesco Garzotto, Alessandra Brendolan, Federico Nalesso, Nicola Marchionna, Monica Zanella, Marco Sartori, Gianfranco B Fiore, Claudio Ronco
High retention onset (HRO) is the designation for a new class of hemodialysis membranes. A unique characteristic of this class is the highly selective and controlled porosity resulting in sieving properties that provide a clinically desirable balance between middle/large molecular weight solute removal and albumin loss. Another defining feature of this membrane class is the relatively small fiber diameter, which produces high convective volumes in the form of internal filtration. The aim of the present study was to estimate, by semi-empirical methods, convective volumes for 2 new HRO dialyzers: Theranova 400 and Theranova 500 (Baxter International Inc...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910794/membrane-innovation-in-dialysis
#13
Adriana Boschetti-de-Fierro, Werner Beck, Helmut Hildwein, Bernd Krause, Markus Storr, Carina Zweigart
Despite advances in renal replacement therapy, the adequate removal of uremic toxins over a broad molecular weight range remains one of the unmet needs in hemodialysis. Therefore, membrane innovation is currently directed towards enhanced removal of uremic toxins and increased membrane permeability. This chapter presents a variety of opportunities where innovation is brought into dialysis membranes. It covers the membrane formation from solution, describing different approaches to control the phase inversion process through additives that either swell in the polymer solution or influence the pore shrinkage during the membrane drying process...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910788/uremia-retention-molecules-and-clinical-outcomes
#14
Fellype Carvalho Barreto, Daniela Veit Barreto, Maria Eugênia Fernandes Canziani
Chronic kidney disease is characterized by the accumulation of organic compounds in the bloodstream that may exert a variety of toxic effects in the body. These compounds, collectively known as uremic toxins, may be classified according to their physicochemical properties as free water-soluble low molecular weight molecules, middle molecules or protein-bound uremic toxins. Most of these retention molecules, due to either their size and/or binding to protein, constitute a complex therapeutic challenge to the nephrologist, particularly in end-stage renal disease, because of their limited removal by conventional dialysis therapies...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910787/middle-molecule-uremic-toxins-and-outcomes-in-chronic-kidney-disease
#15
Ziad A Massy, Sophie Liabeuf
In patients with chronic kidney disease (CKD), uremic toxins constitute a specific nontraditional risk factor. Research in this field started in the early 1990s, and a growing body of preclinical and epidemiological evidence suggests that elevated levels of uremic toxins are associated with poor outcomes in a CKD setting. The present review focuses on a specific class of uremic toxins (the "middle molecules"), which includes well-known candidates like beta-2 microglobulin and fibroblast growth factor 23. Here, we summarize the epidemiological evidence linking the middle-molecule uremic toxin (and especially the larger ones) with hard clinical end points...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28910786/the-evolving-patterns-of-uremia-unmet-clinical-needs-in-dialysis
#16
Xueqing Yu
End-stage renal disease (ESRD) has become a challenging health problem worldwide. Currently, ESRD patients treated with hemodialysis mainly undergo low-flux hemodialysis, high-flux hemodialysis (HF-HD), or hemodiafiltration (HDF). The clearance of middle and large molecules is, however, quite insufficient as regards HF-HD, HDF, and on-line HDF. An unsatisfactory prognosis has led to improved dialysis technology and materials; both protein-leaking membranes and high cut-off membranes increase the clearance of uremic toxin, but in clinical application they may induce albumin loss...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28905671/microbiota-derived-uremic-retention-solutes-perpetrators-of-altered-nonrenal-drug-clearance-in-kidney-disease
#17
Alexander J Prokopienko, Thomas D Nolin
Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease...
September 14, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28904431/role-of-gut-derived-uremic-toxins-on-oxidative-stress-and-inflammation-in-patients-with-chronic-kidney-disease
#18
S Gouroju, P V L N Srinivasa Rao, A R Bitla, K S Vinapamula, S M Manohar, S Vishnubhotla
Several cardiovascular disease (CVD) risk factors have been identified among patients with chronic kidney disease (CKD). Gut-derived uremic toxins (GDUT) are important modifiable contributors in this respect. There are very few Indian studies on GDUT changes in CKD. One hundred and twenty patients older than 18 years diagnosed with CKD were enrolled along with forty healthy subjects. The patients were classified into three groups of forty patients based on stage of CKD. Indoxyl sulfate (IS), para cresyl sulfate (p-CS), indole acetic acid (IAA), and phenol were estimated along with the assessment of oxidative stress (OS), inflammatory state, and bone mineral disturbance...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28902232/advanced-glycation-end-products-ages-accumulation-in-skin-relations-with-chronic-kidney-disease-mineral-and-bone-disorder
#19
Renata de Almeida França, André de Barros Albuquerque Esteves, Cynthia de Moura Borges, Kélcia Rosana da Silva Quadros, Luiz Carlos Nogueira Falcão, Jacqueline Costa Teixeira Caramori, Rodrigo Bueno de Oliveira
Introduction: Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients...
August 28, 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/28900874/effect-of-renal-transplantation-on-cognitive-function-in-hemodialysis-patients-a-longitudinal-study
#20
Yogesh K Chhabra, Sanjay Sood, Omprakash Rathi, Sandeep Mahajan
BACKGROUND: The literature notes high prevalence of cognitive function (CF) impairment among hemodialysis patients. Renal transplantation by reversing metabolic factors should improve cognitive function; however, results in post-transplant patients are inconsistent. Lack of longitudinal studies, variable and small patient population, variable renal function and post-transplantation period and use of non-specific tests make results difficult to interpret. We looked at CF in stable hemodialysis patients just prior to live renal transplantation and approximately 3 months subsequently using well-validated electrophysiological study of P300 cognitive potential obtained by auditory oddball paradigm using multiple scalp electrodes...
September 12, 2017: International Urology and Nephrology
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