Haemolytic Uraemic Syndrome is a thrombotic microangiopathy which predominantly affects children, manifesting as a triad of haemolytic anaemia, thrombocytopenia, and acute kidney injury, with characteristically abnormal renal imaging.
Description
Haemolytic Uraemic Syndrome (HUS) is a life-threatening, complex condition characterised by the triad of microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. It is most commonly encountered in paediatrics and is a leading cause of acute renal failure in children.
Pathogenesis
The pathogenesis of HUS typically involves damage to the endothelial cells of the glomeruli, caused by bacterial toxins, complement pathway dysregulation, or other unidentified factors. This damage leads to platelet aggregation, thrombosis, and consequent haemolysis. The damage to the kidney’s filtration system then leads to proteinuria and haematuria, culminating in acute kidney injury.
Subtypes
HUS is often categorised into two types based on the underlying cause:
- Typical HUS (90% of cases): Associated with gastroenteritis, usually caused by Shiga toxin-producing bacteria, primarily Escherichia coli
- Atypical HUS (aHUS, 10% of cases): Often associated with genetic mutations affecting the regulation of the complement system.
Epidemiology, Risk Factors & Associations
- Most common in children under 5 years of age.
- E. coli infection is the most common precipitating factor in typical HUS (particularly E. coli O157:H7).
- Familial cases of aHUS are often linked to mutations in genes controlling the complement system.
Clinical Features
The classic triad of symptoms for HUS includes:
- Haemolytic anaemia
- Acute kidney injury
- Thrombocytopenia
Patients often present following a gastrointestinal illness with bloody diarrhoea.
Complications
While not a malignant condition, HUS can lead to severe complications, such as:
- Acute kidney injury (can progress to chronic kidney disease)
- Hypertensive crisis
- Neurological complications (e.g., seizures, stroke)
Pathological Features
Histopathology
- Macroscopic: Kidneys may be swollen and pale.
- Microscopic: Characterised by thrombotic microangiopathy (occlusion of small vessels), glomerular thrombosis, and cortical necrosis.
Serology
Elevated lactate dehydrogenase (LDH), decreased haptoglobin, detection of schistocytes on a blood smear are indicative of haemolysis.
Biochemistry
Evidence of renal impairment (elevated urea and creatinine), electrolyte imbalances, and low platelet count.
Radiological Features
General Features
- Renal imaging usually reveals enlarged and oedematous kidneys during the acute phase.
- Long-term damage can lead to renal atrophy.
CT
- Non-contrast: Enlarged kidneys with hypodense parenchyma due to oedema.
- Contrast-enhanced: Poor cortical enhancement in the nephrographic phase due to impaired renal function.
MRI
- T1WI: Hypointense renal parenchyma.
- T2WI: Hyperintense renal parenchyma due to oedema.
- DWI/ADC: Diffusion restriction can be seen in the acute phase.
US
- B-mode: Enlarged kidneys with increased cortical echogenicity.
- Colour Doppler: May show reduced blood flow due to thrombosis.
Diagnosis
Diagnosis of HUS is primarily clinical, supported by laboratory findings (evidence of haemolytic anaemia, thrombocytopenia, and renal impairment). Renal biopsy, although not always necessary, can confirm the diagnosis.
Differential Diagnosis
- Thrombotic thrombocytopenic purpura: Features a similar triad but also includes fever and neurological symptoms.
- DIC (Disseminated Intravascular Coagulation): May have similar laboratory findings but is typically associated with a different clinical context (e.g., severe sepsis).
- Other causes of acute kidney injury.
Management
Management typically involves supportive care, plasma exchange for aHUS, and dialysis for severe renal impairment. Patients should be referred to nephrology for further care, and genetic counselling may be appropriate in cases of aHUS.