Prophylactic use of Eculizumab in patients with aHUS at time of renal transplantation

Patients with complement-mediated aHUS have a risk of recurrent disease in the transplant graft following transplantation. The risk of aHUS relapse is in part determined by the underlying genetic or acquired complement defect. We can screen for abnormalities in patients with a suspected diagnosis of aHUS prior to their transplant to inform of the risk of relapse and to allow a recommendation of if and/or when to recommend treatment with eculizumab.

Patients who have a complement abnormality following testing or if there is a history of recurrent [unexplained TMA] might benefit from treatment with eculizumab at time of transplantation.

Patients with aHUS who are being considered for renal transplantation should be discussed with the National aHUS service. Prophylactic use of eculizumab at time of transplantation can can be pre-approved on a case by case basis.

*if screening for complement abnormalities has not yet been performed, these can be requested here

**a transplanting centre may wish to order in eculizumab on a named patient basis to ensure drug is available when a patient is called up for transplantation – see below.

Management of de-novo TMA following transplantation (post-transplant TMA) is discussed separately.

Post-Transplant TMA

Guidelines for Prophylactic Eculizumab Use

The guidelines make recommendations about the management of patients with atypical haemolytic uraemic syndrome (aHUS) who are being considered for transplantation. The guidelines have been developed specifically to consider the use of prophylactic Eculizumab to prevent aHUS recurrence after transplantation. The guidelines are aimed at healthcare professionals responsible for the assessment and treatment of these patients.

Detailed guidelines on using prophylactic Eculizumab for adult aHUS patients undergoing kidney transplantation are available  here.

Ordering eculizumab for pre-approved patients

Our aHUS specialist nurses have been working closely with clinical teams at transplanting centres to understand some of the issues with obtaining eculizumab quickly at time of transplantation. Alexion now offer a process that allows a transplanting centre to purchase the first two doses of eculizumab on a named patient basis in advance of the drug being required. If the drug is not used for that patient before expiry (because the patient was not transplanted within that timeframe), Alexion will provide replacement stock without further charge.

Detailed information about the service offered by Alexion and how to access this is available here.

Alternatively you can contact us via email ahus.nurses@nhs.net or telephone us on 0191 28 20385

Summary of recommendations for managing patients with aHUS undergoing kidney transplantation

Pre-transplantation:

 The risk of recurrence should be assessed based on genetic screening, presence of autoantibodies and previous transplant history.
 Patients with high or medium risk of recurrence should be offered prophylactic Eculizumab treatment.
 Patients at low risk should be warned of the risk of recurrence and monitored closely.

Treatment: Dosing

 Recommendation: Adult patients should receive eculizumab as follows:

Day 0 – 900mg to be completed prior to the start of surgery

Day 1* – 900mg

Day 7 – 900mg

Day 14 – 900mg

Day 21 – 900mg

Day 28 – 1200mg

Day 42 – 1200mg

*A further dose of eculizumab should be considered if there is significant blood loss requiring administration of FFP or equivalent. The dose and dosing schedule should be adjusted for body weight in children as per paediatric dosing schedule.

Post-Transplant complement blockade monitoring

We would recommend complement blockade is measured in patients undergoing kidney transplantation with concomitant eculizumab as below:

Day 7 – Pre-dose (trough) eculizumab

Day 42 – Immediately prior (trough) to 2nd 1200mg eculizumab dose being given

Annually thereafter [or as clinically indicated where there is suspicion that the complement system may not be adequately blocked]

The blood form for requesting the collection and processing of complement blockade bloods can be found here or by contacting the aHUS Specialist Nurses on ahus.nurses@nhs.net

Treatment: Additional Considerations

 A further dose of Eculizumab should be considered if there is significant blood loss requiring administration of FFP or equivalent.
 Treatment with Eculizumab should continue unless withdrawn with close monitoring as part of a clinical study.
 Patients should receive a Tacrolimus based immunosuppressive regime. The use of anti-IL2 receptor blocking antibody, anti-proliferative agent and steroids should be as per local protocols.
 Rapamycin should be avoided post-transplant in patients at risk of recurrent aHUS.
 Pre-transplant plasma exchange is not required in patients with aHUS prior to transplantation when Eculizumab is being used.
 The guidelines for the prevention of meningococcal disease should be adhered to in all patients with aHUS who are being assessed for kidney transplantation.
 There is a relative contraindication with respect to living related donation but this can be considered in certain circumstances.
 The possibility of liver transplantation should be discussed with all patients considering transplantation but is not the recommended option for most patients.

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