scholarly journals Clinical Course and the Role of Shiga Toxin–ProducingEscherichia coliInfection in the Hemolytic‐Uremic Syndrome in Pediatric Patients, 1997–2000, in Germany and Austria: A Prospective Study

2002 ◽  
Vol 186 (4) ◽  
pp. 493-500 ◽  
Author(s):  
Angela Gerber ◽  
Helge Karch ◽  
Franz Allerberger ◽  
Hege M. Verweyen ◽  
Lothar B. Zimmerhackl
Keyword(s):  
Prospective Study ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Pediatric Patients ◽  
Clinical Course ◽  
Uremic Syndrome ◽  
A Prospective Study

Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS)

2018 ◽  
Vol 33 (11) ◽  
pp. 2057-2071 ◽  
Author(s):  
Ramon Alfonso Exeni ◽  
Romina Jimena Fernandez-Brando ◽  
Adriana Patricia Santiago ◽  
Gabriela Alejandra Fiorentino ◽  
Andrea Mariana Exeni ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Pathogenic Role ◽  
Uremic Syndrome

scholarly journals Absence of interleukin-10 reduces progression of shiga toxin-induced hemolytic uremic syndrome

2021 ◽  
Vol 135 (3) ◽  
pp. 575-588
Author(s):  
Gonzalo Ezequiel Pineda ◽  
Bárbara Rearte ◽  
María Florencia Todero ◽  
Andrea Cecilia Bruballa ◽  
Alan Mauro Bernal ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Renal Damage ◽  
Polymorphonuclear Neutrophils ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Urea ◽  
Tnf Α ◽  
Uremic Syndrome ◽  
Anti Inflammatory

Abstract Hemolytic Uremic Syndrome (HUS), a disease triggered by Shiga toxin (Stx), is characterized by hemolytic anemia, thrombocytopenia and renal failure. The inflammatory response mediated by polymorphonuclear neutrophils (PMNs) and monocytes is essential to HUS onset. Still, the role of anti-inflammatory cytokines is less clear. The deficiency of IL-10, an anti-inflammatory cytokine, leads to severe pathology in bacterial infections but also to beneficial effects in models of sterile injury. The aim of this work was to analyze the role of IL-10 during HUS. Control and IL-10 lacking mice (IL-10−/−) were intravenously injected with Stx type 2 (Stx2) and survival rate was evaluated. PMN and circulating and renal pro- and anti-inflammatory factors were analyzed by FACS and enzyme-linked immunosorbent assay (ELISA) respectively. IL-10−/− mice showed a higher survival associated with lower renal damage reflected by reduced plasma urea and creatinine levels than control mice. Circulating PMN increased at 72 h in both mouse strains accompanied by an up-regulation of CD11b in control mice. In parallel, renal PMN were significantly increased only in control mice after toxin. Plasma TNF-α, IL-6 and corticosterone levels were higher increased in IL-10−/− than control mice. Simultaneously renal TNF-α raised constantly but was accompanied by increased TGF-β levels in IL-10−/− mice. These results demonstrate that the profile of circulating and renal cytokines after Stx2 differed between strains suggesting that balance of these factors could participate in renal protection. We conclude that IL-10 absence has a protective role in an experimental model of HUS by reducing PMN recruitment into kidney and renal damage, and increasing mice survival.

scholarly journals Carboxypeptidase B2 Is Protective in a Mouse Model of Shiga Toxin-Induced Hemolytic Uremic Syndrome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2804-2804
Author(s):  
Toshihiko Nishimura ◽  
John Morser ◽  
Zhifei Shao ◽  
Lawrence L. Leung
Keyword(s):  
Mouse Model ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Conflicts Of Interest ◽  
Severe Thrombocytopenia ◽  
E Coli ◽  
Potential Efficacy ◽  
Significant Difference ◽  
Uremic Syndrome

Abstract Hemolytic uremic syndrome (HUS) is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The most common cause of HUS is Shiga toxin (STX)-producing E. coli, and eculizumab, a monoclonal antibody against complement C5, has shown clinical efficacy in some patients. Carboxypeptidase B2 (CPB2) is a metalloprotease activated by the thrombin/thrombomodulin complex that inactivates a number of inflammatory mediators, including complement C3a, and C5a by removing their C-terminal arginine. We hypothesized that in a murine model of STX-induced HUS, Cpb2-/- mice would have exacerbated disease compared to wild type (WT) mice due to excessive C3a and/or C5a in the absence of CPB2. A mouse model of STX-induced HUS was established by giving STX and LPS toxins intraperitoneally. Cpb2-/- mice had worse survival than WT (37% survival vs. 87% at 48h, p=0.0156). At 48h, severe thrombocytopenia developed in both WT and Cpb2-/- mice (WT: 0.096x106/μL; Cpb2-/-: 0.054x106/μL) compared to controls (1.2x106/μL; p>0.0001 vs. either WT or Cpb2-/-), with Cpb2-/- mice showing worse thrombocytopenia. Renal insufficiency was worse in Cpb2-/- mice than WT mice (BUN at 48h: 85 mg/dL vs. 37 mg/dL, p=0.0074; creatinine: 1.33 mg/dL vs. 0.23 mg/dL; p=0.0112, for Cpb2-/- and WT mice respectively, compared with normal baseline BUN and creatinine of 19 mg/dL and 0.1 mg/dL). Cpb2-/- mice developed worse anemia than WT (hemoglobin 9.8 g/dL vs. 12.4 g/dL, p=0.001 in Cpb2-/- vs. WT mice respectively). At 48h, liver function was worse in Cpb2-/- mice than WT mice, while plasma LDH was increased in Cpb2-/- mice more than WT mice. Using a standardized health score, the Cpb2-/- mice were worse than WT mice at all time points. Thus this model recapitulates STX-induced HUS with the Cpb2-/- mice having worse disease than WT. If the animals were treated with STX alone, there were no deaths in either genotype at 48h and only 37.5% mortality in Cpb2-/- mice by 60h compared with no deaths in WT mice. BUN, creatinine, liver enzymes and LDH were increased in both genotypes treated with STX alone compared to untreated mice, but there was no significant difference between the genotypes. Treatment with LPS alone caused thrombocytopenia in both WT and Cpb2-/- mice and LDH, BUN and creatinine levels were higher in Cpb2-/- mice than in WT mice, but there was no death at 48h and no drop in hemoglobin. Thus while either STX alone or LPS alone caused pathological conditions in the mice, the typical triad of HUS was only present when STX and LPS were given in combination. The Cpb2-/- mice had worse disease than WT mice consistent with our hypothesis on the role of CPB2 in inactivating C3a and/or C5a in STX-induced HUS. The potential efficacy of C3a and/or C5a blockade and anti-thrombotic agents will be tested in this model. Disclosures No relevant conflicts of interest to declare.

Escherichia coli O157:H7 as the Predominant Pathogen Associated With the Hemolytic Uremic Syndrome: A Prospective Study in the Pacific Northwest

PEDIATRICS ◽  
1987 ◽  
Vol 80 (1) ◽  
pp. 37-40
Author(s):  
Marguerite A. Neill ◽  
Phillip I. Tarr ◽  
Carla R. Clausen ◽  
Dennis L. Christie ◽  
Robert O. Hickman
Keyword(s):  
Escherichia Coli ◽  
Prospective Study ◽  
Hemolytic Uremic Syndrome ◽  
Pacific Northwest ◽  
Enteric Pathogens ◽  
Escherichia Coli O157 ◽  
E Coli ◽  
The Pacific ◽  
Uremic Syndrome ◽  
A Prospective Study

During a 12-month period, 14 patients with the hemolytic uremic syndrome were identified in a prospective study of enteric pathogens associated with this disorder. Of the 12 patients with a diarrheal illness preceding the onset of hemolytic uremic syndrome, fecal Escherichia coli O157:H7 was detected in seven (58%), all of whom had bloody diarrhea. Half of the siblings of these patients had concurrent nonbloody diarrhea. No source for infection with this organism was identified. Enteric infection with E coli O157:H7 occurs in the majority of cases of hemolytic uremic syndrome following diarrheal illness in the Pacific Northwest and may represent a previously overlooked cause of hemolytic uremic syndrome in other locales. Evaluation of all cases of hemolytic uremic syndrome for enteric pathogens should routinely include cultures for E coli O157:H7 until results of additional studies clarify the distribution of agents associated with hemolytic uremic syndrome in different geographic regions. These findings may provide new opportunities for the design of therapeutic and preventive strategies in this disorder.

scholarly journals Role of Polymorphonuclear Leukocytes in the Pathophysiology of Typical Hemolytic Uremic Syndrome

2007 ◽  
Vol 7 ◽  
pp. 1155-1164 ◽  
Author(s):  
Ramón A. Exeni ◽  
Gabriela C. Fernández ◽  
Marina S. Palermo
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Poor Prognosis ◽  
Polymorphonuclear Leukocytes ◽  
Cell Damage ◽  
Experimental Models ◽  
Pathogenic Factor ◽  
Gram Negative ◽  
Uremic Syndrome

Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx), through an interaction with its globotriaosylceramide (Gb3) receptor. Although, Stx is the main pathogenic factor and necessary for HUS development, clinical and experimental evidence suggest that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS) and neutrophils (PMN) represent two central components of inflammation during a Gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. In the present review, we discuss the contribution of experimental models and patient's studies in an attempt to elucidate the pathogenic mechanisms of HUS.

scholarly journals Shiga Toxin Activates Complement and Binds Factor H: Evidence for an Active Role of Complement in Hemolytic Uremic Syndrome

2009 ◽  
Vol 182 (10) ◽  
pp. 6394-6400 ◽  
Author(s):  
Dorothea Orth ◽  
Abdul Basit Khan ◽  
Asma Naim ◽  
Katharina Grif ◽  
Jens Brockmeyer ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Active Role ◽  
Factor H ◽  
Uremic Syndrome

scholarly journals Shiga toxin producing Escherichia coli-associated diarrhea and hemolytic uremic syndrome in young children in Romania

Gut Pathogens ◽  
2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Oana Falup-Pecurariu ◽  
Raluca Ileana Lixandru ◽  
Emanuela Cojocaru ◽  
Katalin Csutak ◽  
Vlad Monescu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Young Children ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Clinical Information ◽  
Surveillance Program ◽  
Industrialized Countries ◽  
E Coli ◽  
Uremic Syndrome ◽  
A Prospective Study

Abstract Background Diarrheagenic Escherichia coli (E. coli) is an important cause of diarrheal diseases in both developing countries and industrialized countries. An outbreak of hemolytic uremic syndrome (HUS) in young children from southern Romania was reported in early 2016 and was attributed to Shiga toxin producing E. coli (STEC) O26 infection. The aim of this study was to determine the prevalence, demographic and clinical characteristics of STEC infections in children hospitalized with diarrhea in Brașov in the central region of Romania. We also described the occurrence of HUS among hospitalized children, close in time to the 2016 HUS outbreak in southern Romania. Methods A prospective study was conducted between March and December 2016 among 722 children aged 1–30 months hospitalized with acute diarrhea. Stool samples obtained from patients with diarrhea were tested for the presence of Shiga toxin type 1 (STX1) and type 2 (STX2) by an immunochromatographic assay, and other enteropathogens. Demographic and clinical information on cases of HUS diagnosed in the same hospital was obtained from medical records. Results Overall 46/722 (6.4%) children (mean age 10.3 months, 32.6% females) hospitalized with diarrhea tested positive for STX1 or STX2; of these 79% were positive for both STX1 and STX2, 16% for STX2 only, and 5% for STX1 only. Bloody diarrhea, vomiting and fever were documented in 32.6%, 52.1% and 50.0%, respectively of patients with STEC infection. Eleven confirmed HUS cases (mean age 20 months, five females) were identified between 2014 and 2016 with prodromal diarrhea reported in 10 of them. Three of the 11 HUS patients required hemodialysis. Conclusions STEC prevalence among young children with diarrhea in Romania was high and the risk of HUS is emerging. The establishment of a systematic laboratory-based surveillance program including identification of the circulating STEC strains coupled with epidemiological investigation of HUS patients is warranted to determine the source and mode of transmission of STEC and prevent of STEC-associated diarrhea and HUS.

Acute Myocarditis and Eculizumab Caused Severe Cholestasis in a 17-Month-Old Child Who Has Hemolytic Uremic Syndrome Associated with Shiga Toxin-Producing Escherichia coli

2020 ◽  
Author(s):  
Osman Yesilbas ◽  
Can Yilmaz Yozgat ◽  
Nurver Akinci ◽  
Sirin Sonmez ◽  
Eser Tekin ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Single Dose ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Pediatric Patients ◽  
Acute Myocarditis ◽  
First Case ◽  
Cardiovascular Involvement ◽  
Uremic Syndrome ◽  
Myocardial Involvement

AbstractCardiovascular involvement is uncommon in pediatric patients with hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC-HUS). We presented a case of 17-month-old toddler who had a sporadic type of STEC-HUS complicated by acute myocarditis. The patient was successfully treated by a single dose of eculizumab after six doses of therapeutic plasma exchange (TPE) were inefficient to prevent the cardiac complication. Hepatotoxicity was observed after a single dose of eculizumab. Hepatic and cholestatic enzyme levels slowly returned to normal within 6 months. To the best of our knowledge, this is the first case of myocarditis/cardiomyopathy treated with eculizumab in STEC-HUS. This case illustrates the need for vigilance regarding myocardial involvement and eculizumab-induced hepatotoxicity in STEC-HUS.

scholarly journals Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic syndrome

2002 ◽  
Vol 62 (4) ◽  
pp. 1338-1348 ◽  
Author(s):  
Graciela I. Dran ◽  
Gabriela C. Fernández ◽  
Carolina J. Rubel ◽  
Emilse Bermejo ◽  
Sonia Gomez ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Protective Role ◽  
Uremic Syndrome
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