scholarly journals Shiga Toxin 2a–Induced Endothelial Injury in Hemolytic Uremic Syndrome: A Metabolomic Analysis

2015 ◽  
Vol 213 (6) ◽  
pp. 1031-1040 ◽  
Author(s):  
Christian Betzen ◽  
Kathrin Plotnicki ◽  
Farnoosh Fathalizadeh ◽  
Kirk Pappan ◽  
Thomas Fleming ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Endothelial Injury ◽  
Metabolomic Analysis ◽  
Uremic Syndrome

scholarly journals Heme as Possible Contributing Factor in the Evolvement of Shiga-Toxin Escherichia coli Induced Hemolytic-Uremic Syndrome

2020 ◽  
Vol 11 ◽  
Author(s):  
Kioa L. Wijnsma ◽  
Susan T. Veissi ◽  
Sem de Wijs ◽  
Thea van der Velden ◽  
Elena B. Volokhina ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Plasma Levels ◽  
Nuclear Translocation ◽  
Kidney Injury ◽  
High Plasma ◽  
Endothelial Injury ◽  
Heme Oxygenase 1 ◽  
Uremic Syndrome

Shiga-toxin (Stx)-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) is one of the most common causes of acute kidney injury in children. Stx-mediated endothelial injury initiates the cascade leading to thrombotic microangiopathy (TMA), still the exact pathogenesis remains elusive. Interestingly, there is wide variability in clinical presentation and outcome. One explanation for this could be the enhancement of TMA through other factors. We hypothesize that heme, as released during extensive hemolysis, contributes to the etiology of TMA. Plasma levels of heme and its scavenger hemopexin and degrading enzyme heme-oxygenase-1 (HO-1) were measured in 48 STEC-HUS patients. Subsequently, the effect of these disease-specific heme concentrations, in combination with Stx, was assessed on primary human glomerular microvascular endothelial cells (HGMVECs). Significantly elevated plasma heme levels up to 21.2 µM were found in STEC-HUS patients compared to controls and were inversely correlated with low or depleted plasma hemopexin levels (R2 −0.74). Plasma levels of HO-1 are significantly elevated compared to controls. Interestingly, especially patients with high heme levels (n = 12, heme levels above 75 quartile range) had high plasma HO-1 levels with median of 332.5 (86–720) ng/ml (p = 0.008). Furthermore, heme is internalized leading to a significant increase in reactive oxygen species production and stimulated both nuclear translocation of NF-κB and increased levels of its target gene (tissue factor). In conclusion, we are the first to show elevated heme levels in patients with STEC-HUS. These increased heme levels mediate endothelial injury by promoting oxidative stress and a pro-inflammatory and pro-thrombotic state. Hence, heme may be a contributing and driving factor in the pathogenesis of STEC-HUS and could potentially amplify the cascade leading to TMA.

Tissue-resident macrophages mediate neutrophil recruitment and kidney injury in shiga toxin-induced hemolytic uremic syndrome.

2021 ◽  
Author(s):  
Julia K. Lill ◽  
Stephanie Thiebes ◽  
Judith-Mira Pohl ◽  
Jenny Bottek ◽  
Nirojah Subramaniam ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Kidney Injury ◽  
Neutrophil Recruitment ◽  
Uremic Syndrome

scholarly journals Hemoconcentration and predictors in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS)

2021 ◽  
Author(s):  
Sebastian Loos ◽  
Jun Oh ◽  
Laura van de Loo ◽  
Markus J. Kemper ◽  
Martin Blohm ◽  
...  
Keyword(s):  
Risk Factor ◽  
Serum Creatinine ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Neurological Symptoms ◽  
Fluid Loss ◽  
Good Prediction ◽  
E Coli ◽  
Complicated Course ◽  
Uremic Syndrome

Abstract Background Hemoconcentration has been identified as a risk factor for a complicated course in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS). This single-center study assesses hemoconcentration and predictors at presentation in STEC-HUS treated from 2009–2017. Methods Data of 107 pediatric patients with STEC-HUS were analyzed retrospectively. Patients with mild HUS (mHUS, definition: max. serum creatinine < 1.5 mg/dL and no major neurological symptoms) were compared to patients with severe HUS (sHUS, definition: max. serum creatinine ≥ 1.5 mg/dL ± major neurological symptoms). Additionally, predictors of complicated HUS (dialysis ± major neurological symptoms) were analyzed. Results Sixteen of one hundred seven (15%) patients had mHUS. Admission of patients with sHUS occurred median 2 days earlier after the onset of symptoms than in patients with mHUS. On admission, patients with subsequent sHUS had significantly higher median hemoglobin (9.5 g/dL (3.6–15.7) vs. 8.5 g/dL (4.2–11.5), p = 0.016) than patients with mHUS. The product of hemoglobin (g/dL) and LDH (U/L) (cutoff value 13,302, sensitivity 78.0%, specificity of 87.5%) was a predictor of severe vs. mild HUS. Creatinine (AUC 0.86, 95% CI 0.79–0.93) and the previously published score hemoglobin (g/dL) + 2 × creatinine (mg/dL) showed a good prediction for development of complicated HUS (AUC 0.87, 95% CI 0.80–0.93). Conclusions At presentation, patients with subsequent severe STEC-HUS had a higher degree of hemoconcentration. This underlines that fluid loss or reduced fluid intake/administration may be a risk factor for severe HUS. The good predictive value of the score hemoglobin (g/dL) + 2 × creatinine (mg/dL) for complicated HUS could be validated in our cohort. Graphical abstract

scholarly journals Whole-genome characterization of hemolytic uremic syndrome-causing Shiga toxin-producing Escherichia coli in Sweden

Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1296-1305
Author(s):  
Ying Hua ◽  
Milan Chromek ◽  
Anne Frykman ◽  
Cecilia Jernberg ◽  
Valya Georgieva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Whole Genome ◽  
Genome Characterization ◽  
Uremic Syndrome

scholarly journals Hemolytic Uremic Syndrome Associated withEscherichia coliO8:H19 and Shiga Toxin 2f Gene

2015 ◽  
Vol 21 (1) ◽  
pp. 168-169 ◽  
Author(s):  
Ingrid H.M. Friesema ◽  
Mandy G. Keijzer-Veen ◽  
Marja Koppejan ◽  
Henk S. Schipper ◽  
Arjanne J. van Griethuysen ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Uremic Syndrome

scholarly journals Therapeutic use of a receptor mimic probiotic reduces intestinal Shiga toxin levels in a piglet model of hemolytic uremic syndrome

2014 ◽  
Vol 7 (1) ◽  
Author(s):  
Shannon J Hostetter ◽  
Amy F Helgerson ◽  
James C Paton ◽  
Adrienne W Paton ◽  
Nancy A Cornick
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Therapeutic Use ◽  
Uremic Syndrome

scholarly journals First Shiga Toxin-ProducingEscherichia coliIsolate from a Patient with Hemolytic Uremic Syndrome, Brazil

2002 ◽  
Vol 8 (5) ◽  
pp. 535-536 ◽  
Author(s):  
Beatriz Ernestina C. Guth ◽  
Renato Lopes de Souza ◽  
Tânia Mara I. Vaz ◽  
Kinue Irino
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Uremic Syndrome

Outbreak of Shiga Toxin–Producing Escherichia coli (STEC) O104:H4 Infection in Germany Causes a Paradigm Shift with Regard to Human Pathogenicity of STEC Strains

2012 ◽  
Vol 75 (2) ◽  
pp. 408-418 ◽  
Author(s):  
LOTHAR BEUTIN ◽  
ANNETT MARTIN
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Outbreak Strain ◽  
Fenugreek Seeds ◽  
E Coli ◽  
Aggregative Adherence ◽  
Uremic Syndrome ◽  
Enterocyte Effacement ◽  
The Way

An outbreak that comprised 3,842 cases of human infections with enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104:H4 occurred in Germany in May 2011. The high proportion of adults affected in this outbreak and the unusually high number of patients that developed hemolytic uremic syndrome makes this outbreak the most dramatic since enterohemorrhagic E. coli (EHEC) strains were first identified as agents of human disease. The characteristics of the outbreak strain, the way it spread among humans, and the clinical signs resulting from EAHEC infections have changed the way Shiga toxin–producing E. coli strains are regarded as human pathogens in general. EAHEC O104:H4 is an emerging E. coli pathotype that is endemic in Central Africa and has spread to Europe and Asia. EAHEC strains have evolved from enteroaggregative E. coli by uptake of a Shiga toxin 2a (Stx2a)–encoding bacteriophage. Except for Stx2a, no other EHEC-specific virulence markers including the locus of enterocyte effacement are present in EAHEC strains. EAHEC O104:H4 colonizes humans through aggregative adherence fimbrial pili encoded by the enteroaggregative E. coli plasmid. The aggregative adherence fimbrial colonization mechanism substitutes for the locus of enterocyte effacement functions for bacterial adherence and delivery of Stx2a into the human intestine, resulting clinically in hemolytic uremic syndrome. Humans are the only known natural reservoir known for EAHEC. In contrast, Shiga toxin–producing E. coli and EHEC are associated with animals as natural hosts. Contaminated sprouted fenugreek seeds were suspected as the primary vehicle of transmission of the EAHEC O104:H4 outbreak strain in Germany. During the outbreak, secondary transmission (human to human and human to food) was important. Epidemiological investigations revealed fenugreek seeds as the source of entry of EAHEC O104:H4 into the food chain; however, microbiological analysis of seeds for this pathogen produced negative results. The survival of EAHEC in seeds and the frequency of human carriers of EAHEC should be investigated for a better understanding of EAHEC transmission routes.

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