Eculizumab In The Treatment of aHUS
The National aHUS service will consider patients with a potential diagnosis of aHUS for treatment with eculizumab. These patients should be discussed with the National aHUS service as guided by our EMERGENCY REFERRAL pathway.
The National aHUS service will consider patients with aHUS who have end-stage renal failure and may benefit from the prophylactic use of eculizumab at time of renal transplantation.
What is Eculizumab?
Eculizumab is a recombinant, humanised, monoclonal antibody directed against C5. It binds C5 thus preventing its cleavage by C3bBbC3b, therefore inhibiting the terminal pathway.
Eculizumab has replaced plasma exchange as the gold-standard in the management of complement mediated primary aHUS in adults and children. Eculizumab is given in the treatment of aHUS in the native kidney and also to prevent recurrence of aHUS following renal transplantation.
Initial Treatment of Patients with Suspected aHUS
We recommend that all patients with a potential new diagnosis of complement mediated primary aHUS are offered treatment with eculizumab. The earlier treatment with eculizumab is initiated the greater the chance of recovery of renal function. Although all investigations on the diagnostic checklist must be undertaken at initial presentation in adults only the ADAMTS13 activity must be available prior to authorisation of Eculizumab. Until this is available we recommend that plasma therapy is undertaken where appropriate.
In children due to the rarity of TTP and the difficulty of plasma exchange Kidney Disease: Improving Global Outcomes (KDIGO) recommended that Eculizumab can be commenced prior to the ADAMTS13 result with the caveat that clinical deterioration on eculizumab should necessitate immediate plasma therapy.
Prophylactic use of Eculizumab in patients with aHUS at time of renal transplantation
In patients requiring renal transplantation with a diagnosis of complement mediated aHUS there is a risk of recurrent disease in the allograft. The risk of aHUS relapse is in part determined by the underlying genetic or acquired complement defect. Guidance for clinicians who have a patient with aHUS who are being considered for renal transplantation is available in the next section on eculizumab and transplantation.