Hemolytic uremic syndrome

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 4 Apr 2025

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

Full details

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

Full details

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

Full details

Diagnostic tests

1st tests 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

Full details

Tests to consider

urinalysis
ADAMTS13 level
LFTs
serum amylase, lipase, glucose

Full details

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.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Fakhouri F, Zuber J, Frémeaux-Bacchi V, et al. Haemolytic uraemic syndrome. Lancet. 2017 Aug 12;390(10095):681-96. Abstract

Banatvala N, Griffin PM, Greene KD, et al. The United States national prospective hemolytic uremic syndrome study: microbiologic, serologic, clinical and epidemiologic findings. J Infect Dis. 2001 Apr 1;183(7):1063-70. Abstract

Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005 Mar 19-25;365(9464):1073-86. Abstract

Wong CS, Jelacic S, Habeeb RL, et al. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000 Jun 29;342(26):1930-6.Full text Abstract

McKee RS, Schnadower D, Tarr PI, et al; Pediatric Emergency Medicine Collaborative Research Committee and Pediatric Emergency Research Canada. Predicting hemolytic uremic syndrome and renal replacement therapy in Shiga toxin-producing Escherichia coli-infected children. Clin Infect Dis. 2020 Apr 10;70(8):1643-51.Full text Abstract

Loirat C, Fakhouri F, Ariceta G, et al; HUS International. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016 Jan;31(1):15-39. Abstract

Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli O157:H7 and the hemolytic uremic syndrome. N Engl J Med. 1995 Aug 10;333(6):364-8. Abstract

Rathbone J, Kaltenthaler E, Richards A, et al. A systematic review of eculizumab for atypical haemolytic uraemic syndrome (aHUS). BMJ Open. 2013 Nov 4;3(11):e003573.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

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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 tests

1st tests to order

Tests 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

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice