Hemolytic uremic syndrome

Last reviewed: 28 Oct 2023

Last updated: 22 Jun 2022

Hemolytic uremic syndrome (HUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.

Most cases of HUS occur in children and are diarrhea-associated (D+ HUS). Diarrhea-associated HUS is usually caused by Shiga toxin-producing Escherichia coli.

Rarely other organisms, such as Shigella and Streptococcus pneumoniae, are implicated.

Acute kidney injury necessitating dialysis develops in approximately half of children with diarrhea-associated HUS.

Adequate hydration is important to minimize renal damage in HUS associated with Shiga toxin-producing E coli infections. Avoidance of antibiotics, antimotility agents, and nonsteroidal anti-inflammatory drugs is advised. Cautious use of opioids is advised; there are insufficient data on the effect of opioids on the course of HUS.

Anemia can be treated with red cell transfusion. Platelet transfusions are generally avoided in the absence of active bleeding.

Atypical HUS can occur due to genetic or acquired abnormalities in the alternative complement regulatory pathway. HUS can also occur as a secondary phenomenon due to medications, cancer, and other systemic diseases.

Definition

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Ninety percent of HUS cases occur in the pediatric population, due to Shiga toxin-producing Escherichia coli (STEC).[1][2]

Atypical HUS occurs due to abnormalities in the alternative complement regulatory pathway, resulting in endothelial cell damage and causing microvascular thrombosis. Atypical HUS can occur in adults and children.[3]

History and exam

Key diagnostic factors

diarrhea, especially bloody diarrhea
childhood, especially age <5 years

More key diagnostic factors

Other diagnostic factors

known community outbreak of Shiga toxin-producing E coli
history of ingestion of food that may have been contaminated with Shiga toxin-producing E coli
unusual adverse effect following treatment with cyclosporine, some chemotherapy agents, targeted cancer agents, and quinine
pregnancy or postpartum status
unusual adverse effect following bone marrow transplant
family history of possible HUS-like syndrome

Other diagnostic factors

Risk factors

ingestion of contaminated food or water
known community outbreak of toxicogenic E coli
exposure to infected individuals in institutional settings
genetic predisposition (atypical HUS)
bone marrow transplant
exposure to cyclosporine, some chemotherapy agents, targeted cancer agents, and quinine
pregnancy- or postpartum-related

More risk factors

Diagnostic investigations

1st investigations to order

CBC
peripheral blood smear
renal function/creatinine
serum electrolytes (sodium, potassium, chloride and bicarbonate, calcium and phosphorus)
prothrombin time (PT), PTT
LDH
haptoglobin
stool culture on sorbitol-MacConkey agar to detect Shiga toxin-producing Escherichia coli
polymerase chain reaction (PCR) to detect Shiga toxin 1/Shiga toxin 2
proteins involved in complement regulation

More 1st investigations to order

Investigations to consider

urinalysis
ADAMTS13 level
LFTs
serum amylase, lipase, glucose

More investigations to consider

Treatment algorithm

ACUTE

Shiga toxin-producing Escherichia coli (STEC) HUS

atypical HUS

secondary HUS: not due to Streptococcus pneumoniae

secondary HUS: due to S pneumoniae

Contributors

Authors

Sharon Andreoli, MD

Byron P. and Francis D. Hollet Professor of Pediatrics, Pediatric Nephrology

Indiana University School of Medicine

Indianapolis

Disclosures

SA owns stock in Merck and Pfizer, and has been a consultant for Reata Pharmaceuticals. SA is on the Editorial Board of Pediatric Nephrology and the Journal of Pediatrics.

Myda Khalid, MD

Associate Professor of Pediatric Nephrology

Indiana University School of Medicine

Indianapolis

Disclosures

MK declares that she has no competing interests.

Acknowledgements

Dr Sharon Andreoli and Dr Myda Khalid would like to gratefully acknowledge Dr Ann Zimrin and Dr John Hess, previous contributors to this topic.

Disclosures

AZ and JH declare that they have no competing interests.

Peer reviewers

Rebecca Connor, MD

Chief Fellow

Section of Hematology and Oncology

Department of Internal Medicine

Wake Forest University Baptist Medical Center

Winston-Salem

Disclosures

RC declares that she has no competing interests.

Differentials
- Thrombotic thrombocytopenic purpura (TTP)
- Malignant hypertension
- Systemic lupus erythematosus (SLE)
More Differentials
Guidelines
- Guidelines on hemolytic uremic syndrome by Indian Society of Pediatric Nephrology: key messages
- Hemolytic uremic syndrome in a developing country: consensus guidelines
More Guidelines
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Hemolytic uremic syndrome

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

Shiga toxin-producing Escherichia coli (STEC) HUS

atypical HUS

secondary HUS: not due to Streptococcus pneumoniae

secondary HUS: due to S pneumoniae

Contributors

Authors

Sharon Andreoli, MD

Disclosures

Myda Khalid, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Rebecca Connor, MD

Disclosures

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

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