Diarrhea-associated hemolytic uremic syndrome in southern Alberta: A long-term single-centre experience

Grisaru, Silviu; Midgley, Julian; Hamiwka, Lorraine; Wade, Andrew; Samuel, Susan

doi:10.1093/pch/16.6.337

Cited by 14 publications

(14 citation statements)

References 15 publications

(27 reference statements)

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“…In North America and Europe, 0.72 to 1.44 cases of HUS per 100,000 population are reported each year [7]. The largest outbreak of HUS in Europe took place between the months of May and July 2011 and began in northern Germany.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Rescues Neurovascular Unit Integrity from Cell Damage Caused by Systemic Administration of Shiga Toxin 2 and Lipopolysaccharide in Mice Motor Cortex

et al. 2013

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Shiga toxin 2 (Stx2)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome (HUS) that can lead to fatal encephalopathies. Neurological abnormalities may occur before or after the onset of systemic pathological symptoms and motor disorders are frequently observed in affected patients and in studies with animal models. As Stx2 succeeds in crossing the blood-brain barrier (BBB) and invading the brain parenchyma, it is highly probable that the observed neurological alterations are based on the possibility that the toxin may trigger the impairment of the neurovascular unit and/or cell damage in the parenchyma. Also, lipopolysaccharide (LPS) produced and secreted by enterohemorrhagic Escherichia coli (EHEC) may aggravate the deleterious effects of Stx2 in the brain. Therefore, this study aimed to determine (i) whether Stx2 affects the neurovascular unit and parenchymal cells, (ii) whether the contribution of LPS aggravates these effects, and (iii) whether an inflammatory event underlies the pathophysiological mechanisms that lead to the observed injury. The administration of a sub-lethal dose of Stx2 was employed to study in detail the motor cortex obtained from a translational murine model of encephalopathy. In the present paper we report that Stx2 damaged microvasculature, caused astrocyte reaction and neuronal degeneration, and that this was aggravated by LPS. Dexamethasone, an anti-inflammatory, reversed the pathologic effects and proved to be an important drug in the treatment of acute encephalopathies.

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Section: Introductionmentioning

confidence: 99%

Dexamethasone Rescues Neurovascular Unit Integrity from Cell Damage Caused by Systemic Administration of Shiga Toxin 2 and Lipopolysaccharide in Mice Motor Cortex

et al. 2013

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“…In mild cases of D+HUS in previously healthy children, the azotemia may be missed or difficult to document as serum creatinine levels can be within normal range despite a more than 50% increase from baseline. 16 D+HUS is a systemic disease that can affect many organs; however, some of the most serious complications relate to involvement of the central nervous system. Lethargy, which is observed in many patients on presentation, can progress to development of stupor and coma as well as seizures and strokes.…”

Section: Clinical Presentation D+husmentioning

confidence: 99%

“…The highest incidence of D+HUS is reported among children younger than 6 years who typically present in the late summer and autumn months. 8,14,16,[22][23][24][25] Prevalence of D+HUS is closely related to the incidence of EHEC infections and the main reservoir for EHEC pathogens is the gastrointestinal tract of healthy cattle. 26 Higher incidence of D+HUS in rural areas with a developed cattle industry has been reported.…”

Section: Epidemiologymentioning

confidence: 99%

“…8,23 The highest incidence of D+HUS in the world was reported in Argentina, while, in Canada, it has been observed in the province of Alberta; both geographic regions have developed beef production industries. 16,27 Large outbreaks originating in contaminated food have been extensively publicized; one of the most well-known outbreaks in the US was caused by contaminated ground beef hamburgers served in a restaurant chain, hence the popular name for D+HUS: "hamburger disease". 5 However, contrary to popular belief, most cases of D+HUS are sporadic or occur in small clusters and are not related to poorly cooked contaminated ground beef.…”

Section: Epidemiologymentioning

confidence: 99%

“…16,18 Nevertheless, a significant percentage are affected by long-term, mostly renal, sequelae. Unlike mortality rate, risk for long-term renal sequelae has not significantly changed over the years, remaining, on average, around 30%.…”

Section: Complement Inhibitorsmentioning

confidence: 99%

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Management of hemolytic-uremic syndrome in children

Grisaru¹

2014

IJNRD

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Acute renal failure associated with a fulminant, life-threatening systemic disease is rare in previously healthy young children; however, when it occurs, the most common cause is hemolytic-uremic syndrome (HUS). In most cases (90%), this abrupt and devastating illness is a result of ingestion of food or drink contaminated with pathogens that produce very potent toxins. Currently, there are no proven treatment options that can directly inactivate the toxin or effectively interfere with the cascade of destructive events triggered by the toxin once it gains access to the bloodstream and binds its receptor. However, HUS is self-limited, and effective supportive management during the acute phase is proven to be a life saver for children affected by HUS. A minority of childhood HUS cases, approximately 5%, are caused by various genetic mutations causing uncontrolled activation of the complement system. These children, who used to have a poor prognosis leading to end-stage renal disease, now have access to exciting new treatment options that can preserve kidney function and avoid disease recurrences. This review provides a summary of the current knowledge on the epidemiology, pathophysiology, and clinical presentation of childhood HUS, focusing on a practical approach to best management measures.

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Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coli

et al. 2017

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IMPORTANCEThe associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear.OBJECTIVE To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals.DATA SOURCES MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched.STUDY SELECTION Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. DATA EXTRACTION AND SYNTHESISTwo reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models.MAIN OUTCOMES AND MEASURES Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy).RESULTS Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I 2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I 2 = 17%), and death (OR, 5.13 [95% CI,; I 2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I 2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]).CONCLUSIONS AND RELEVANCE Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

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Diarrhea-associated hemolytic uremic syndrome in southern Alberta: A long-term single-centre experience

Cited by 14 publications

References 15 publications

Dexamethasone Rescues Neurovascular Unit Integrity from Cell Damage Caused by Systemic Administration of Shiga Toxin 2 and Lipopolysaccharide in Mice Motor Cortex

Dexamethasone Rescues Neurovascular Unit Integrity from Cell Damage Caused by Systemic Administration of Shiga Toxin 2 and Lipopolysaccharide in Mice Motor Cortex

Management of hemolytic-uremic syndrome in children

Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coli

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