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Uremic toxins

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https://www.readbyqxmd.com/read/28211788/hemolytic-uremic-syndrome-complicated-by-clostridium-septicum-bacteremia-and-new-onset-type-1-diabetes-mellitus-report-of-a-case%C3%A2
#1
Anna C Iddings, Asha N Shenoi, Alba Morales Pozzo, Stefan G Kiessling
We report the unusual case of a 5-year-old male hospitalized for management of diabetic ketoacidosis (DKA) and new-onset type 1 diabetes mellitus (T1DM) who developed acute renal injury secondary to hemolytic uremic syndrome (HUS). He was diagnosed with Shiga toxin-producing entero-hemorrhagic Escherichia coli (EHEC) 0157:H7-positive HUS 48 hours after being diagnosed with new-onset T1DM/DKA. His hospital course was complicated by Clostridium septicum sepsis with colonic perforation. This patient's diagnosis of new-onset T1DM just prior to HUS is novel...
February 17, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28202171/residual-renal-function-a-paradigm-shift
#2
Jerome Lowenstein, Jared J Grantham
Residual renal function (RRF) in patients undergoing dialysis treatments is currently viewed as glomerular filtrate that has escaped tubular reabsorption. RRF has been quantified as a clearance of urea or creatinine, or urea + creatinine. A major paradigm shift has followed the recognition that a substantial number of organic anion retention solutes (possible "uremic toxins") are protein-bound and therefore are not readily filtered. These protein-bound aryl compounds are secreted by renal tubular organic anion transporters (OATs)...
March 2017: Kidney International
https://www.readbyqxmd.com/read/28202164/manipulating-the-gut-microbiome-to-decrease-uremic-toxins
#3
Rabi Yacoub, Christina M Wyatt
The uremic solute indoxyl sulfate has been associated with increased mortality and other adverse outcomes in patients with chronic kidney disease. In a recent study published in Cell Host & Microbe, Devlin et al. describe a novel approach to alter the production of indoxyl sulfate through manipulation of the gut microbiota. Although this approach is far from clinical application, it may allow investigators to determine the contribution of uremic solutes to disease pathogenesis.
March 2017: Kidney International
https://www.readbyqxmd.com/read/28198690/thrombotic-microangiopathies-similar-presentations-different-therapies
#4
REVIEW
Gerald B Appel
Thrombotic thrombocytopenic purpura, Shiga toxin hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and antiphospholipid syndrome are thrombotic microangiopathies that present similarly but arise from different causes. Management depends on distinguishing them promptly and providing targeted therapy.
February 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28185299/incremental-hemodialysis-a-european-perspective
#5
Kamonwan Tangvoraphonkchai, Andrew Davenport
Most patients initiating hemodialysis have residual renal function (RRF). Whereas RRF is monitored prior to commencing hemodialysis, once dialysis is started most centres simply rely on dialyzer urea clearance to determine adequate uremic toxin clearance and disregard the effect of RRF. However sustaining RRF is important for the dialysis patient, as RRF reduces inter-dialytic weight gains, increases middle molecule and protein bound toxin clearances and is associated with better quality of life assessments...
February 9, 2017: Seminars in Dialysis
https://www.readbyqxmd.com/read/28180952/endothelial-dysfunction-during-long-term-follow-up-in-children-with-stec-hemolytic-uremic-syndrome
#6
Martin Kreuzer, Laura Sollmann, Stephan Ruben, Maren Leifheit-Nestler, Dagmar-Christiane Fischer, Lars Pape, Dieter Haffner
BACKGROUND: Shiga-toxin-producing Escherichia coli (STEC)-associated hemolytic-uremic syndrome (HUS) is a major cause of acute kidney injury (AKI), especially in children. Its long-term outcome with respect to endothelial damage remains largely elusive. METHODS: This was a cross-sectional study in 26 children who had suffered from STEC-HUS in the past and achieved a complete recovery of renal function (eGFR >90 ml/min/1.73 m(2)). Skin microcirculation after local heating was assessed by laser Doppler fluximetry, carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (cIMT), 24-h ambulatory blood pressure, and angiopoietin (Ang) 1 and 2 serum levels after a median follow-up period of 6...
February 8, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28178427/pathogenesis-of-colitis-in-germ-free-mice-infected-with-ehec-o157-h7
#7
K A Eaton, C Fontaine, D I Friedman, N Conti, C J Alteri
Enterohemorrhagic Escherichia coli (EHEC) are strains of E. coli that express Shiga toxins (Stx) and cause hemorrhagic colitis. In some cases, disease can progress to hemolytic uremic syndrome, a potentially fatal form of kidney disease. Both enteric and renal disease are associated with the expression of stx genes, which are often carried on lysogenic phage. Toxin is expressed following induction and conversion of the phage to lytic growth. The authors previously used a germ-free mouse model to demonstrate that toxin gene expression is enhanced during growth in vivo and that renal disease is dependent on both prophage induction and expression of Stx2...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28178155/complement-mediated-thrombotic-microangiopathy-secondary-to-sepsis-induced-disseminated-intravascular-coagulation-successfully-treated-with-eculizumab-a-case-report
#8
Tomohiro Abe, Akira Sasaki, Taichiro Ueda, Yoshitaka Miyakawa, Hidenobu Ochiai
Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA secondary to sepsis- induced coagulopathy, who was successfully treated with eculizumab.A 44-year-old woman, who had no special medical history or familial history of TMAs, was admitted on suspicion of septic shock...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28176471/subclinical-atypical-haemolytic-uremic-syndrome-relapse-following-discontinuation-of-eculizumab
#9
REVIEW
Shi Zhou Choo, Fiona Brown
A 25-year-old man presented with microangiopathic haemolytic anaemia and acute kidney injury. With a normal ADAMTS-13 level, negative faecal shiga-toxin test and strong family history of atypical haemolytic uremic syndrome, he was commenced on eculizumab to good clinical response. Subsequent genetic testing revealed a heterozygous complement factor H mutation. Eculizumab was discontinued after 44 months of treatment, and he relapsed within 6 months, with the first sign being downtrending haptoglobin levels, with no other markers of haemolysis or thrombocytopaenia, 5 weeks prior to development of acute kidney injury...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28158302/host-cell-interactions-of-outer-membrane-vesicle-associated-virulence-factors-of-enterohemorrhagic-escherichia-coli-o157-intracellular-delivery-trafficking-and-mechanisms-of-cell-injury
#10
Martina Bielaszewska, Christian Rüter, Andreas Bauwens, Lilo Greune, Kevin-André Jarosch, Daniel Steil, Wenlan Zhang, Xiaohua He, Roland Lloubes, Angelika Fruth, Kwang Sik Kim, M Alexander Schmidt, Ulrich Dobrindt, Alexander Mellmann, Helge Karch
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28146081/p-cresyl-sulfate
#11
REVIEW
Tessa Gryp, Raymond Vanholder, Mario Vaneechoutte, Griet Glorieux
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...
January 29, 2017: Toxins
https://www.readbyqxmd.com/read/28134751/efficacy-of-urtoxazumab-tma-15-humanized-monoclonal-antibody-specific-for-shiga-toxin-2-against-post-diarrheal-neurological-sequelae-caused-by-escherichia-coli-o157-h7-infection-in-the-neonatal-gnotobiotic-piglet-model
#12
Rodney A Moxley, David H Francis, Mizuho Tamura, David B Marx, Kristina Santiago-Mateo, Mojun Zhao
Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 × 10⁸ colony-forming units of EHEC O157:H7 strain EDL933 (Stx1⁺, Stx2⁺) when 22-24 h old...
January 26, 2017: Toxins
https://www.readbyqxmd.com/read/28122514/indoxyl-sulfate-the-uremic-toxin-linking-hemostatic-system-disturbances-with-the-prevalence-of-cardiovascular-disease-in-patients-with-chronic-kidney-disease
#13
Tomasz W Kamiński, Krystyna Pawlak, Małgorzata Karbowska, Michał Myśliwiec, Dariusz Pawlak
BACKGROUND: During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play. The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition. METHODS: Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study...
January 25, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28107445/beta-glucans-supplementation-associates-with-reduction-in-p-cresyl-sulfate-levels-and-improved-endothelial-vascular-reactivity-in-healthy-individuals
#14
Carmela Cosola, Maria De Angelis, Maria Teresa Rocchetti, Eustacchio Montemurno, Valentina Maranzano, Giuseppe Dalfino, Carlo Manno, Annapaola Zito, Michele Gesualdo, Marco Matteo Ciccone, Marco Gobbetti, Loreto Gesualdo
BACKGROUND: Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD)...
2017: PloS One
https://www.readbyqxmd.com/read/28089476/serum-asymmetric-and-symmetric-dimethylarginine-and-morbidity-and-mortality-in-hemodialysis-patients
#15
Tariq Shafi, Thomas H Hostetter, Timothy W Meyer, Seungyoung Hwang, Xin Hai, Michal L Melamed, Tanushree Banerjee, Josef Coresh, Neil R Powe
BACKGROUND: Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. STUDY DESIGN: Post hoc analysis of the Hemodialysis (HEMO) Study. SETTING & PARTICIPANTS: 1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization...
January 12, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28089366/limited-reduction-in-uremic-solute-concentrations-with-increased-dialysis-frequency-and-time-in-the-frequent-hemodialysis-network-daily-trial
#16
Tammy L Sirich, Kara Fong, Brett Larive, Gerald J Beck, Glenn M Chertow, Nathan W Levin, Alan S Kliger, Natalie S Plummer, Timothy W Meyer
The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10...
January 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28077371/markers-of-endothelial-damage-in-patients-with-chronic-kidney-disease-on-hemodialysis
#17
Andrés Carmona, Maria Luisa Agüera, Carlos Luna Ruiz, Paula Buendia, Laura Calleros, Andrea Garcia-Jerez, Manuel Rodríguez-Puyol, Manuel Arias, Marta Arias-Guillen, Gabriel de Arriba, Jose Ballarin, Carmen Bernis, Elvira Fernandez, Sagrario Garcia-Rebollo, Javier Mancha, Gloria Del Peso, Estefania Perez, Esteban Poch, Jose M Portoles, Diego Rodriguez-Puyol, Rafael Sánchez-Villanueva, Felipe Sarro, Armando Torres, Alejandro Martin-Malo, Pedro Aljama, Rafael Ramirez, Julia Carracedo
Patients with stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (REDinREN, Madrid): 80 patients with diabetes mellitus (DM) and 80 patients without DM who were matched for clinical and demographic criteria...
January 11, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28075397/the-sulfur-metabolite-lanthionine-evidence-for-a-role-as-a-novel-uremic-toxin
#18
REVIEW
Alessandra F Perna, Miriam Zacchia, Francesco Trepiccione, Diego Ingrosso
Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis...
January 10, 2017: Toxins
https://www.readbyqxmd.com/read/28067862/impact-of-indoxyl-sulfate-on-progenitor-cell-related-neovascularization-of-peripheral-arterial-disease-and-post-angioplasty-thrombosis-of-dialysis-vascular-access
#19
REVIEW
Chih-Cheng Wu, Szu-Chun Hung, Ko-Lin Kuo, Der-Cherng Tarng
Patients with chronic kidney disease (CKD) have an increased risk of vascular disease, which is associated with considerable health care costs. Vascular disease in CKD differs clinically and pathobiologically from that in patients with normal renal function. Besides the traditional risk factors, retention of uremic toxins contributes to the pathogenesis of vascular disease in patients with CKD. Indoxyl sulfate is a protein-bound uremic toxin and is inefficiently removed by conventional dialysis. Accumulating evidence suggests that indoxyl sulfate is a vascular toxin involved in atherosclerosis, arteriosclerosis, vascular calcification and vascular repair...
January 7, 2017: Toxins
https://www.readbyqxmd.com/read/28067473/role-of-uremic-toxins-on-apoptosis-with-varying-periods-of-hemodialysis
#20
Zeynep Hünkerler, Tülay Köken, Buğra Koca, Ahmet Kahraman
Increased apoptotic cell death in uremic patients has been confirmed by a variety of studies. The present study aimed to investigate the effect of uremic toxins and duration of hemodialysis (HD) therapy on apoptosis by means of measuring serum caspase cleaved CK18 (CCCK-18) levels. Seventy chronic HD patients were recruited and divided into three groups with differing periods of HD, from 6 months to 10 years. Twelve healthy subjects served as controls. Serum CCCK-18 level was found significantly higher in HD patient groups (Group 2; 189 ± 71 IU/L, Group 3; 182 ± 65 IU/L, Group 4; 204 ± 111 IU/L) as compared to the control group (122 ± 20 U/L) (P < 0...
February 2017: Therapeutic Apheresis and Dialysis
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