Hyponatremia: a new predictor of mortality in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome

Alconcher, Laura; Coccia, Paula; Suarez, Ángela; Monteverde, Marta Lidia; Gutiérrez, María Graciela Perez Y; Carlopio, Paula M; Missoni, Mabel; Balestracci, Alejandro; Principi, Illiana; Ramirez, Flavia; Estrella, Patricia; Micelli, Susana; Leroy, Daniela C; Quijada, Nahir E; Seminara, Claudia; Giordano, Marta I; Solís, Susana B Hidalgo; Saurit, Mariana; Caminitti, Alejandra; Arias, A. Martínez; Rivas, Marta; Risso, Paula; Liern, Miguel

doi:10.1007/s00467-018-3991-6

Cited by 54 publications

(50 citation statements)

References 13 publications

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“…Neurological damage produced by Stx2 (Ashkenazi et al, 1994;Siegler, 1994) has gained notoriety in Argentina and throughout the world. A multicenter, observational, retrospective, and cross-sectional study recently conducted by the National Epidemiological Surveillance System of Argentina concluded that central nervous system (CNS) involvement by STEC was the main predictor of death in patients with HUS (Alconcher et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Environmental Cues Modulate Microglial Cell Behavior Upon Shiga Toxin 2 From Enterohemorrhagic Escherichia coli Exposure

Berdasco

Vega

Rosato-Siri

et al. 2020

Front. Cell. Infect. Microbiol.

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Shiga toxin (Stx) produced by enterohemorrhagic E. coli produces hemolytic uremic syndrome and encephalopathies in patients, which can lead to either reversible or permanent neurological abnormalities, or even fatal cases depending on the degree of intoxication. It has been observed that the inflammatory component plays a decisive role in the severity of the disease. Therefore, the objective of this work was to evaluate the behavior of microglial cell primary cultures upon Stx2 exposure and heat shock or lipopolysaccharide challenges, as cues which modulate cellular environments, mimicking fever and inflammation states, respectively. In these contexts, activated microglial cells incorporated Stx2, increased their metabolism, phagocytic capacity, and pro-inflammatory profile. Stx2 uptake was associated to receptor globotriaosylceramide (Gb3)-pathway. Gb3 had three clearly distinguishable distribution patterns which varied according to different contexts. In addition, toxin uptake exhibited both a Gb3-dependent and a Gb3-independent binding depending on those contexts. Altogether, these results suggest a fundamental role for microglial cells in pro-inflammatory processes in encephalopathies due to Stx2 intoxication and highlight the impact of environmental cues.

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Section: Introductionmentioning

confidence: 99%

Environmental Cues Modulate Microglial Cell Behavior Upon Shiga Toxin 2 From Enterohemorrhagic Escherichia coli Exposure

Berdasco

Vega

Rosato-Siri

et al. 2020

Front. Cell. Infect. Microbiol.

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“…In this model, only leukocytosis and hyponatremia also resulted independently correlated with higher risk of CNS manifestations in these patients. Previous studies had shown that leukocytosis was associated with a higher risk of poor prognosis ( 39 , 40 ) and hyponatremia was even identified as a predictor of death ( 41 ). Probably our findings underline that clinical neurologic outcome depends not only by the direct effects of Stx but also by secondary effects due to activation of the complement system ( 9 , 23 ) and by neuronal cells dehydration due to hyponatremia ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Low C3 Serum Levels Predict Severe Forms of STEC-HUS With Neurologic Involvement

et al. 2020

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Background: The correlation between the severity of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) and involvement of the complement system has been examined in a small number of studies, with conflicting results. In the present study, we investigated whether serum C3 levels on admission are associated with neurologic involvement. Methods: To this purpose, 68 consecutive STEC-HUS patients were recruited and main clinical and laboratory variables ad hospital admission were compared between those with or without neurologic involvement. Results: STEC-HUS patients who developed neurologic involvement (NI) showed significant higher leukocyte count, C-reactive protein and hemoglobin, and lower sodium levels as compared with those without. Interestingly, baseline serum levels of C3 were significantly lower in patients with NI as compared with those without (p < 0.001). Moreover, when stratified according to need of Eculizumab rescue therapy due to severe NI, patients treated with this drug showed baseline C3 serum levels significantly lower than those who were not (p < 0.001). Low C3 was independent risk factor for NI in our patients' population when entered as covariate in a multivariate logistic regression analysis including other major variables previously proposed as possible predictors of poor prognosis in STEC-HUS (for instance, leukocyte count, c-reactive protein, sodium levels) (HR 6.401, 95%CI 1.617-25.334, p = 0.008 for C3). To underline the role of complement in the worsening of STEC-HUS patients' clinical conditions and outcomes, all patients were divided into two groups according to the baseline lower vs. normal serum levels of C3 and the main data on care needs were assessed. Interestingly more patients with lower C3 serum levels required renal replacement therapy (p = 0.024), anti-hypertensive therapy (p = 0.011), Intensive Care Unit admission (p = 0.009), and longer hospitalization (p = 0.003), thus displaying Netti et al. C3 and Severe Neurologic STEC-HUS significantly more severe disease features as compared with those with normal C3 serum levels. Conclusions: Our data suggests that children with STEC-HUS with decreased C3 concentrations at admission are more likely to develop neurologic involvement and are at increased risk of having severe clinical complications.

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“…Brain: A multi-centric, observational, retrospective and cross-sectional study was recently conducted by the Argentine National Epidemiological Surveillance System of HUS concluded that Central Nervous System (CNS) involvement was the main predictor of death in patients suffering from STEC-HUS [16]. In view of the clinical relevance of neurological disorder derived from HUS, neurobiological research in Latin America has been conducted in the past few years and novel information has emerged from this research.…”

Section: Novel Insights About Shiga Toxins and The Immune Responsesmentioning

confidence: 99%

“…Finally, a summary of the organized efforts as a research community to attack the problem of STEC/EHEC infections using the principles of One Health is discussed. Due to the nature of this review, seminal work by groups outside Latin America was not included or referenced; however, the authors want to recommend these excellent reviews and books for further reading [1,7,11,12,13,14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Shiga Toxin-Producing Escherichia coli Research in Latin America

et al. 2018

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Pathogenic Escherichia coli are known to be a common cause of diarrheal disease and a frequently occurring bacterial infection in children and adults in Latin America. Despite the effort to combat diarrheal infections, the south of the American continent remains a hot spot for infections and sequelae associated with the acquisition of one category of pathogenic E. coli, the Shiga toxin-producing E. coli (STEC). This review will focus on an overview of the prevalence of different STEC serotypes in human, animals and food products, focusing on recent reports from Latin America outlining the recent research progress achieved in this region to combat disease and endemicity in affected countries and to improve understanding on emerging serotypes and their virulence factors. Furthermore, this review will highlight the progress done in vaccine development and treatment and will also discuss the effort of the Latin American investigators to respond to the thread of STEC infections by establishing a multidisciplinary network of experts that are addressing STEC-associated animal, human and environmental health issues, while trying to reduce human disease. Regardless of the significant scientific contributions to understand and combat STEC infections worldwide, many significant challenges still exist and this review has focus in the Latin American efforts as an example of what can be accomplished when multiple groups have a common goal.

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Hyponatremia: a new predictor of mortality in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome

Cited by 54 publications

References 13 publications

Environmental Cues Modulate Microglial Cell Behavior Upon Shiga Toxin 2 From Enterohemorrhagic Escherichia coli Exposure

Environmental Cues Modulate Microglial Cell Behavior Upon Shiga Toxin 2 From Enterohemorrhagic Escherichia coli Exposure

Low C3 Serum Levels Predict Severe Forms of STEC-HUS With Neurologic Involvement

Recent Advances in Shiga Toxin-Producing Escherichia coli Research in Latin America

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