What is the immediate management for a patient diagnosed with Hemolytic Uremic Syndrome (HUS)?

Immediate Management of Hemolytic Uremic Syndrome (HUS)

The immediate management of Hemolytic Uremic Syndrome (HUS) should focus on urgent supportive care, with complement inhibitors like eculizumab as the standard of care for atypical HUS, while typical HUS (STEC-HUS) requires supportive management with appropriate fluid and electrolyte balance. 1

Initial Assessment and Diagnosis

• Rapidly distinguish between typical HUS (STEC-HUS) and atypical HUS (aHUS) through first-level laboratory tests including complete blood count with peripheral blood smear, ADAMTS13 activity, and stool testing for verocytotoxin-producing Escherichia coli (VTEC) 1
• The diagnosis of HUS is based on the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, though in almost 50% of cases at onset, not all three clinical signs may be clearly present 2
• The presence of schistocytes >1% favors a diagnosis of thrombotic microangiopathy (TMA), but their absence should not exclude an early diagnosis due to the low sensitivity of this test 2
• If neurological involvement is suspected (occurring in 10-20% of aHUS patients), obtain neurological consultation, electroencephalogram (EEG), and brain MRI 2

Immediate Management Based on HUS Type

For Typical HUS (STEC-HUS):

• Provide supportive care with appropriate fluid and electrolyte management 3, 4
• Initiate antihypertensive therapy if necessary 4
• Begin renal replacement therapy when appropriate (approximately two-thirds of children with HUS will require dialysis) 3, 4
• Avoid antibiotics, antimotility agents, narcotics, and non-steroidal anti-inflammatory drugs as they may worsen outcomes 5
• Maintain optimal hydration for nephroprotection 5

For Atypical HUS (aHUS):

• Treat as a medical emergency with urgent supportive measures 1
• Initiate complement inhibitor therapy (eculizumab or ravulizumab) as soon as possible after confirming diagnosis 1, 6
• For adult patients, eculizumab dosing consists of: 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter 6
• For pediatric patients, dosing is weight-based according to established protocols 6
• Vaccinate against meningococcal infection (serogroups A, C, W, Y, and B) at least 2 weeks prior to initiation of complement inhibitor therapy; if urgent therapy is needed, provide antibacterial prophylaxis and administer vaccines as soon as possible 6

Management of Complications

• Monitor for extrarenal involvement, particularly neurological complications which are the most frequent non-renal complication and first cause of death 5
• For severe neurological involvement, consider early initiation of plasmapheresis which might improve prognosis 5
• For pregnancy-triggered aHUS, C5 inhibitors have been shown to be effective in resolving TMA 2
• Be aware that patients of Chinese and/or Japanese descent may not respond to C5 inhibitors due to polymorphic variants of the C5 gene 2

Prevention of Infectious Complications

• Vaccinate all patients with aHUS against pathogenic organisms as soon as possible 2
• For patients receiving anti-C5 treatment (eculizumab, ravulizumab), administer quadrivalent A, C, W, Y meningococcal vaccine and consider long-term antimicrobial prophylaxis 2, 6

Long-term Monitoring

• Establish a long-term renal follow-up plan for any patient with a history of HUS 5
• When considering discontinuation of complement inhibitor therapy in aHUS patients, thoroughly assess risk factors, as the risk of relapse is between 10-20% after discontinuation 2
• Monitor parameters such as C3, C4, CH50, and AP50 if extending the interval of C5 inhibitor administration 2

Special Considerations

• For patients requiring plasma exchange or fresh frozen plasma infusion, supplemental dosing of complement inhibitors is required 6
• For atypical HUS with genetic predisposition, consider genetic counseling due to possible genetic transmission 1
• A multidisciplinary team approach including specialists from hematology, nephrology, and other relevant fields is essential for managing HUS, especially aHUS 1