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Pathophysiology and clinical complications of atypical-HUS
Review how TMA manifests in atypical-HUS and can lead to resulting organ damage.1
Chronic, uncontrolled complement activity can result in continuous endothelial damage and ongoing risk of TMA1,6,18
Scan through the cyclical stages of endothelial injury that result from TMA lesions to understand how irreversible tissue damage can progress.5,18,19
In individuals with atypical-HUS, uncontrolled complement activity causes ongoing vascular endothelial injury, resulting in TMA lesions and progressive organ damage5,18,19
The assembly of multiple C5b-9 complexes on the surface of endothelial cells causes endothelial injury, leukocyte recruitment, and platelet activation.6,20-22
Binding of C5a to the C5a receptor results in a decrease in the endothelium’s anticomplement and antithrombogenic properties.6,21,24
Disrupted endothelial cells:
- Release complement-activating microparticles, resulting in a vicious cycle of endothelial activation, complement amplification, and ongoing endothelial injury6,25
- Release prothrombotic coagulation proteins, activate platelets, and recruit leukocytes, resulting in the formation of thrombi in small blood vessels throughout the body6
Biomarkers of complement activation, inflammation, endothelial cell activation and damage, coagulation, and renal damage (eg, Ba, sTNFR1, sVCAM-1, D-dimer, U-cystatin C) are similarly elevated among patients with atypical-HUS receiving or not receiving plasma exchange or plasma infusion.26
Ba=complement factor Ba; sTNFR1=soluble tumor necrosis factor receptor-1; sVCAM-1=soluble vascular cell adhesion molecule-1; U-cystatin C=urinary cystatin C.
Patients with atypical-HUS are at ongoing risk of systemic, life-threatening, and progressive complications1,5,8,10
Atypical-HUS patients can show involvement in more than 1 organ system.2,7,27-29*
- Confusion27
- Stroke2
- Encephalopathy2,28
- Seizure27
- Arterial thrombosis2
- Cardiomyopathy27
- Vascular stenosis28
- Myocardial infarction2,28
- Hypertension27
- Colitis2
- Nausea/vomiting2
- Abdominal pain27
- Gastroenteritis8
- Pancreatitis2
- Diarrhea27
- Elevated creatinine27
- Decreased eGFR5
- Proteinuria29
- Peripheral arterial disease30
- Phalangeal gangrene30
*The organ-specific symptoms associated with atypical-HUS are reported from published literature and are not limited to those listed above.
eGFR=estimated glomerular filtration rate; ESRD=end-stage renal disease