Need for Long-term Follow-up in Enterohemorrhagic Escherichia coli–Associated Hemolytic Uremic Syndrome Due to Late-Emerging Sequelae

Rosales, Alejandra; Hofer, Johannes; Zimmerhackl, L. B.; Jungraithmayr, Therese; Riedl, Magdalena; Giner, Thomas; Strasak, Alexander; Orth‐Höller, Dorothea; Würzner, Reinhard; Karch, Helge

doi:10.1093/cid/cis196

Cited by 160 publications

(161 citation statements)

References 38 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…Unlike mortality rate, risk for long-term renal sequelae has not significantly changed over the years, remaining, on average, around 30%. 18,80 Pneumococcal HUS is managed based on similar principles, but tends to be associated with a worse prognosis. 2 Children with identifiable sequelae such as hypertension, proteinuria, or impaired renal function should be treated accordingly; generally, long-term treatment with an angiotensin-converting enzyme inhibitor is indicated.…”

Section: Complement Inhibitorsmentioning

confidence: 99%

“…However, children that seem to have made a full recovery may also benefit from long-term monitoring for development of hypertension and proteinuria, as the extent of lost nephrons during the acute phase of the disease may be significant but masked by compensation of remaining nephrons. 80 aHUS, particularly the familial form, has been reported to be associated with a poor prognosis; without specific treatment, patients experience relapses and ongoing disease activity leading to end-stage kidney failure in most cases. 77 The disease tends to recur after kidney transplantation, leading to graft loss in a majority of patients.…”

Section: Complement Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Management of hemolytic-uremic syndrome in children

Grisaru¹

2014

IJNRD

View full text Add to dashboard Cite

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.

show abstract

Section: Complement Inhibitorsmentioning

confidence: 99%

Section: Complement Inhibitorsmentioning

confidence: 99%

Management of hemolytic-uremic syndrome in children

Grisaru¹

2014

IJNRD

View full text Add to dashboard Cite

show abstract

“…Typical HUS is mainly associated with gastrointestinal infections by Shiga toxin-producing bacteria, foremost Escherichia coli O157:H7, and patients usually present with preceding diarrhea (1,2). Typical HUS constitutes approximately 90% of all HUS cases in children and occurs mainly in children 0.5-3 years of age (3).…”

Section: Introductionmentioning

confidence: 99%

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Hofer¹,

Janecke

Zimmerhackl³

et al. 2013

Clinical Journal of the American Society of Nephrology

Self Cite

125

108

View full text Add to dashboard Cite

SummaryBackground and objectives This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.Design, setting, participants, & measurements A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA. Questionnaires were administered to evaluate the clinical and laboratory data.Results Homozygous deletion in CFHR1 was detected in 32% of the patients with aHUS tested, compared with 2.5% of controls (P,0.001). CFH antibodies were present in 25% of the patients and none of the controls. CFH antibodies were detected in 82% of patients with homozygous CFHR1 gene deletion and in 6% of patients without. CFH antibody-positive patients with aHUS showed a significantly lower platelet nadir at disease onset and significantly less frequent involvement of the central nervous system than did antibody-negative patients. Antibody-positive patients also received plasma therapy more often.Conclusion Homozygous deletion in CFHR1 is strongly associated with occurrence of CFH antibodies in pediatric patients with aHUS. However, despite this apparent genetic disease predisposition, it cannot be considered an exclusive cause for aHUS. Initial presentation of Shiga toxin-negative HUS with severe thrombocytopenia and no central nervous system complications in pediatric patients is especially suspicious for CFH antibody aHUS.

show abstract

“…Following recovery from the acute phase of the disease, proteinuria may persist; such persistence correlates with a poor long-term renal prognosis (20)(21)(22). Injury of podocytes has emerged as the key mechanism underlying this glomerular dysfunction (23) and may have a critical impact on the course of the disease and renal outcome.…”

mentioning

confidence: 99%

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

et al. 2014

Self Cite

View full text Add to dashboard Cite

jHemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38␣ MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option.

show abstract

Need for Long-term Follow-up in Enterohemorrhagic Escherichia coli–Associated Hemolytic Uremic Syndrome Due to Late-Emerging Sequelae

Abstract: This study identified an association between the use of plasma treatment and poor long-term outcome and confirms already known risk factors for poor prognosis. Follow-up investigations for at least 5 years are recommended to detect late-emerging sequelae.

Cited by 160 publications

References 38 publications

Management of hemolytic-uremic syndrome in children

Management of hemolytic-uremic syndrome in children

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

Contact Info

Product

Resources

About