Treatment of Typical (Enteropathic) Hemolytic Uremic Syndrome

Bitzan, Martin; Schaefer, Franz; Reymond, D.

doi:10.1055/s-0030-1262881

Cited by 63 publications

(39 citation statements)

References 139 publications

(207 reference statements)

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“…No available therapy protects patients from acute toxin-mediated cellular injury, including apoptosis. 12,13 Chronic renal affection or failure occurs in up to 10% of patients who survive the acute manifestations of the disease. 13 Our group has identified a novel signaling system that protects against apoptosis.…”

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confidence: 99%

Ouabain Protects against Shiga Toxin–Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL

Burlaka

Liu

Rebetz

et al. 2013

Journal of the American Society of Nephrology

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Hemolytic uremic syndrome, a life-threatening disease often accompanied by acute renal failure, usually occurs after gastrointestinal infection with Shiga toxin 2 (Stx2)-producing Escherichia coli. Stx2 binds to the glycosphingolipid globotriaosylceramide receptor, expressed by renal epithelial cells, and triggers apoptosis by activating the apoptotic factor Bax. Signaling via the ouabain/Na,K-ATPase/IP3R/NF-kB pathway increases expression of Bcl-xL, an inhibitor of Bax, suggesting that ouabain might protect renal cells from Stx2-triggered apoptosis. Here, exposing rat proximal tubular cells to Stx2 in vitro resulted in massive apoptosis, upregulation of the apoptotic factor Bax, increased cleaved caspase-3, and downregulation of the survival factor Bcl-xL; co-incubation with ouabain prevented all of these effects. Ouabain activated the NF-kB antiapoptotic subunit p65, and the inhibition of p65 DNA binding abolished the antiapoptotic effect of ouabain in Stx2-exposed tubular cells. Furthermore, in vivo, administration of ouabain reversed the imbalance between Bax and Bcl-xL in Stx2-treated mice. Taken together, these results suggest that ouabain can protect the kidney from the apoptotic effects of Stx2.

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confidence: 99%

Ouabain Protects against Shiga Toxin–Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL

Burlaka

Liu

Rebetz

et al. 2013

Journal of the American Society of Nephrology

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“…The duration of renal failure, haemolysis, and thrombocytopenia, and the long-term outcome were all similar in both control and treated groups. Furthermore, haemorrhagic complications were more common in these trials [57][58][59]. Accordingly, antithrombotic agents are not recommended in patients with STEC-induced HUS because there is no evidence of clinical benefit, and there is an increased risk of haemorrhagic complications.…”

Section: Antithrombotic Agentsmentioning

confidence: 99%

Hemolytic Uremic Syndrome Caused by Shiga Toxin-Producing Escherichia coli Infections: An Overview

Abdullah¹,

Al-Sultan

Jassim³

et al. 2014

Clon Transgen

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The purpose of this manuscript is to provide a current overview on the Shiga Toxin / verotoxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) with emphasis on the epidemiology, clinical and laboratory manifestations, pathogenesis, recommended assessment, treatment strategies and prognosis. Hemolytic uremic syndrome (HUS) is a cause of the community-acquired acute renal insufficiency in young children. The outbreak in Germany illustrated both the emerging importance of non-O157 serotypes as agents of human disease and the potential for large-scale methods of food production and distribution to result in widespread disease. Children with STEC-induced HUS typically have a prodromal illness that can rapidly develop severe and multisystem life-threatening complications. STEC infection is acquired through contaminated food or water. Thrombotic microangiopathy is the mechanism of the development of the characteristic pathologic lesion of HUS. Any patient with a recent history of diarrhea and signs of a multi-organ disorder requires a proper assessment for the possible development of HUS. Appropriate laboratory testing for both O157 and non-O157 serotypes, as well as prompt initiation of infection control procedures for confirmed or suspected cases, will facilitate follow-up investigation to identify the source of disease and will help to prevent secondary transmission. Currently, diagnostic test to predict which patients will develop HUS is not available. Supportive care and intravenous fluid replacement are the cornerstones of treatment because of the current lack of safe and specific therapeutic intervention. Culizumab and/or plasma treatment may be considered in patients with severe CNS involvement who have a poor prognosis. None of the multiple therapeutic agents including antithrombotic agents, plasma exchange and/or plasma infusion, tissue-type plasminogen activator, and oral Shiga toxin-binding agent that have been used is recommended. For most patients with uncomplicated STEC-associated gastroenteritis who are treated with supportive care, the prognosis was excellent. Public health interventions are the key to prevent STEC-associated diarrhea and HUS. Researches will improve the care of patients with different HUS types in the years to come. The identification of genetic factors associated with HUS will contribute to a better insight of the pathogenesis of HUS and will have potential therapeutic and preventive implications.

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“…New findings suggest that STX also directly interferes with the alternative complement pathway and that it is a key pathogenic mechanism. 10 Thrombocytopenia is the first abnormality in STEC infections, either the patient develops HUS or not, and lasts up to one week. It is secondary to thrombocyte consumption and somewhat to voluminous expansion.…”

Section: Pathogenesis and Clinical Presentationmentioning

confidence: 99%

E. coli O104:H4 outbreak and haemolytic–uraemic syndrome

Borgatta¹,

Kmet-Lunaček²,

Rello³

2012

Medicina Intensiva

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Background: The first cases of the European epidemic of Shiga toxin-producing Escherichia coli O104:H4 (STEC-O104:H4) infection were reported in Germany in April 2011. Objectives: To characterize the 2011 STEC-O104:H4 outbreak and its management. A literature review is made to assess the state of the art in STEC---haemolytic---uraemic syndrome (HUS) epidemiology, pathogenesis, management and prognosis, focusing on critically ill adults. Methods: References were obtained from the European Center for Disease Control and World Health Organization epidemiological updates, in addition to a PubMed search covering the period from 1980 to August 2011, including all published work on STEC-014:H4 and reviews on HUS management and prognosis. Results: The epidemic originated from a bean and seed sprouts farm in Lower Saxony, and was caused by the O104:H4 strain ---a highly antibiotic resistant, hybrid enteroaggregative ---Shiga toxin producing E. coli strain (STEC). The infection was characterized by increased HUS (25%) and a higher mortality rate. STEC enteritis and HUS are associated with significant mortality and morbidity, especially amongst patients with severe renal and neurological disorders. Management should center on prompt kidney protection by maintaining adequate renal perfusion, in addition to avoiding diuretics and nephrotoxic agents. Conclusions:The published studies regarding antibiotic treatment lack good quality evidence. However, recent data suggest a potential modulating effect that explains the conflicting data but moreover suggests that azithromycin might be of use. Neutralizing monoclonal antibodies are a promising new therapy for STEC---HUS, with currently ongoing studies. Other treatments have not been shown to be superior to supportive therapy alone. E. coli O104:H4 outbreak and haemolytic---uraemic syndrome 577 PALABRAS CLAVEE. coli O104:H4; STEC-O104; Revisión; Síndrome urémico-hemolítico Brote de E. coli O104:H4 y síndrome hemolítico-urémico ResumenAntecedentes: Los primeros casos de la epidemia europea de infección por E. coli productora de la toxina Shiga (STEC-O104:H4) se detectaron en Alemania en abril de 2011. Objetivos: Caracterizar el brote de STEC-O104:H4 de 2011 y su gestión. Se realiza una revisión bibliográfica para evaluar el estado del arte en epidemiología, patogenia, tratamiento y pronósitico de la STEC-síndrome urémico-hemolítico (SHU), con especial hincapié en los adultos críticamente enfermos. Métodos: Se obtuvieron referencias de las actualizaciones epidemiológicas del Centro Europeo de Control de Enfermedades y de la Organización Mundial de la Salud, además de una búsqueda en PubMed relativa al periodo de 1980 a agosto de 2011, incluidas todas las publicaciones sobre la STEC-014:H4 y las revisiones sobre el tratamiento y el pronóstico del SHU. Resultados: La epidemia tuvo su origen en unos brotes germinados de una plantación de Baja Sajonia y estuvo causada por la cepa O104:H4, una cepa híbrida de E. coli enteroagregativa productora de la toxina Shiga (STEC) con una e...

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Treatment of Typical (Enteropathic) Hemolytic Uremic Syndrome

Cited by 63 publications

References 139 publications

Ouabain Protects against Shiga Toxin–Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL

Ouabain Protects against Shiga Toxin–Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL

Hemolytic Uremic Syndrome Caused by Shiga Toxin-Producing Escherichia coli Infections: An Overview

E. coli O104:H4 outbreak and haemolytic–uraemic syndrome

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