From the Guidelines
Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening form of thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury, and the first-line treatment is eculizumab (Soliris) or ravulizumab (Ultomiris), which are terminal complement inhibitors. The diagnosis of aHUS is based on the presence of hemolytic anemia, thrombocytopenia, and acute kidney injury, with signs and symptoms including bloody diarrhea, decreased urination or blood in the urine, abdominal pain, vomiting, and occasionally fever 1. The treatment of aHUS is focused on inhibiting the complement pathway, which is dysregulated in this condition, and the use of eculizumab or ravulizumab has been shown to be effective in improving outcomes in patients with aHUS 1.
The management of aHUS involves the use of complement inhibitors, such as eculizumab or ravulizumab, which are administered intravenously, with the dosing regimen varying depending on the patient's weight and age. Before starting treatment with eculizumab or ravulizumab, patients must receive meningococcal vaccination at least two weeks prior to treatment due to increased infection risk, and many physicians recommend antibiotic prophylaxis. Plasma exchange or plasma infusion may be used initially while awaiting diagnosis confirmation or in resource-limited settings.
Key points to consider in the management of aHUS include:
- The use of complement inhibitors, such as eculizumab or ravulizumab, as first-line treatment
- The importance of meningococcal vaccination and antibiotic prophylaxis before starting treatment
- The potential need for plasma exchange or plasma infusion in certain situations
- The consideration of kidney transplantation in patients with end-stage renal disease, with the use of complement inhibition to prevent recurrence in the transplanted kidney
- The importance of genetic testing in patients with aHUS, particularly in those with a family history of the condition, to identify potential genetic variants that may be associated with the disease 1.
In terms of genetic evaluation, it is recommended that patients with aHUS undergo genetic testing to identify potential genetic variants that may be associated with the disease, particularly if there is a family history of the condition. This can help to identify patients who may be at risk of developing aHUS and can also inform treatment decisions. Additionally, genetic testing can help to identify patients who may be at risk of developing other conditions, such as focal and segmental glomerulosclerosis (FSGS) or autosomal dominant tubulointerstitial kidney disease (ADTKD), which can also be associated with genetic variants.
From the FDA Drug Label
2 Atypical Hemolytic Uremic Syndrome ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).
2 Atypical Hemolytic Uremic Syndrome (aHUS) SOLIRIS is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.
Atypical HUS type of anemia is associated with complement-mediated thrombotic microangiopathy (TMA).
- Ravulizumab (ULTOMIRIS) and eculizumab (SOLIRIS) are indicated for the treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated TMA 2 3 3.
- These medications can help reduce the risk of thrombotic microangiopathy and improve outcomes in patients with aHUS.
- However, the FDA drug labels do not provide direct information on the type of anemia associated with aHUS.
From the Research
Definition and Characteristics of Atypical HUS
- Atypical hemolytic uremic syndrome (aHUS) is a rare variant of thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment 4.
- aHUS is associated with poor clinical outcomes, high morbidity, and mortality, and predominantly affects the kidneys but can cause multi-organ system dysfunction 4.
- The condition is caused by a genetic abnormality in the complement alternative pathway, resulting in over-activation of the complement system and formation of microvascular thrombi 4, 5.
Diagnosis and Differential Diagnosis
- aHUS is clinically similar to other major thrombotic microangiopathies (TMAs), including Shiga toxin-producing Escherichia coli (STEC)-HUS, thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC) 5.
- Diagnosis of aHUS requires documentation of microangiopathic hemolysis accompanied by thrombocytopenia, and can be distinguished from TTP on the basis of ADAMTS13 activity levels 5, 6.
- aHUS can be distinguished from STEC-HUS through testing for Shiga toxin-producing E. coli, and from TTP by measuring ADAMTS13 activity 5.
Treatment and Management
- Eculizumab, a humanized anti-C5 monoclonal antibody, has been the standard of care for treating aHUS, and has been shown to be effective in improving clinical outcomes 4, 7.
- Ravulizumab, a derivative of eculizumab, has been developed to allow for less frequent administration, and has been shown to be effective in treating aHUS 8, 7.
- Other novel complement inhibitor therapies, including danicopan, crovalimab, and pegcetacoplan, are currently undergoing clinical trials and may offer improved treatment options for aHUS 7.