Emergency: requires immediate attention
Hemolytic uremic syndrome
Alerts and Notices
Synopsis
Shiga toxin damages the renal epithelial cells, mesangial cells, and vascular endothelial cells. Drug toxicity, pregnancy, antiphospholipid antibody syndrome, and systemic lupus erythematosus have also been reported to induce HUS. Cases of HUS not associated with an acute stressor are thought to be caused by complement pathway dysregulation. Gene mutations (C3, C4BPA, C4BPB, MCP, CFB, CFH, CFHR1, CFHR3, CFHR4, CFHR5, CFI, DGKE, and THBD) are identified in approximately 70% of nonstressor-induced HUS.
HUS is a rare condition. In children younger than 5 years of age in the United States and Western Europe, the incidence of Shiga toxin-producing HUS is approximately 2-3 per 100 000 children. Escherichia coli O157:H7 is estimated to account for 90% of these cases. HUS without an identifiable trigger is less common, with an estimated incidence of 7 per one million in this population.
HUS triggered by an infection presents with hematochezia, fever, abdominal pain, nausea, and emesis. Clinical findings related to acute renal failure can include anuria or oliguria, hypertension, elevated creatinine, elevated blood urea nitrogen (BUN), proteinuria, microscopic hematuria, and pyuria. Idiopathic HUS will present without concurrent infectious symptoms. Hemolytic anemia, thrombocytopenia, and acute renal failure can present insidiously with lethargy and uremia, or patients may present with a petechial rash, scattered ecchymosis, or hematuria. In these cases, a family history of HUS can help inform consideration of the diagnosis, as many of the complement pathway mutations are inherited.
Treatment is dependent on severity and is mainly supportive, including fluid replacement, blood product transfusions, avoidance of nephrotoxic medications, and dialysis. HUS can progress to end-stage renal disease requiring renal replacement therapy and ultimately renal transplant. However, prognosis is generally good, especially in children. An estimated 25% of children will have acute renal injury, while approximately 3% develop end-stage renal disease requiring hemodialysis with potential renal transplantation. Pneumococcal-associated HUS has a higher mortality, estimated to be around 12%, with approximately 10% developing end-stage renal disease.
Codes
ICD10CM:D59.3 – Hemolytic Uremic Syndrome
SNOMEDCT:
111407006 – Hemolytic uremic syndrome
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Diagnostic Pearls
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Differential Diagnosis & Pitfalls
- Thrombotic thrombocytopenic purpura
- Drug-induced hemolysis (antibiotics, NSAIDs, antimalarials)
- Autoimmune hemolytic anemia
- Acute interstitial nephritis
- Transfusion reaction
- Glucose-6-phosphate dehydrogenase deficiency
- Lymphoma / leukemia
- Myeloproliferative disease
- Paroxysmal nocturnal hemoglobinuria
- Microangiopathic hemolytic anemia
- Hypersplenism
- Alpha thalassemia, beta thalassemia
- Lead poisoning
- Porphyria (eg, porphyria cutanea tarda)
- Anemia of chronic disease
- Aplastic anemia
- Iron-deficiency anemia
- Megaloblastic anemia (vitamin B12 deficiency, folate deficiency)
- Myelodysplastic syndrome
- Infection (malaria, mononucleosis, babesiosis, etc)
- Idiopathic thrombocytopenic purpura
- Ischemic colitis
- Inflammatory bowel disease (Crohn disease, ulcerative colitis)
- Meckel diverticulum
- Intussusception
- Intestinal volvulus
- Disseminated intravascular coagulation
- Sepsis
- Hereditary spherocytosis and other RBC membrane defects
- Acute kidney injury / acute tubular necrosis
- Glomerulonephritis
- Pyelonephritis
- HELLP syndrome
- Vasculitis
- Systemic lupus erythematosus
- Immunoglobulin A vasculitis (formerly Henoch-Schönlein purpura)
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Management Pearls
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Therapy
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.Subscription Required
References
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Last Reviewed:10/21/2018
Last Updated:09/24/2019
Last Updated:09/24/2019