Eculizumab and Transplantation

Eculizumab and 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. If screening for complement abnormalities has not yet been performed, these can be requested here.

Patients with aHUS who are being considered for renal transplantation should be discussed with the National aHUS service. Prophylactic Eculizumab use is authorised on a case by case basis.

The presentation of de-novo TMA following transplantation is discussed below in the post transplant TMA section.

 

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.

 

Below is a summary of the main recommendations in the guidelines.

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 a single dose of 900mg Eculizumab which is completed prior to the start of surgery. The dose and dosing schedule should be adjusted for body weight in children as per paediatric dosing schedule.

● Recommendation: Adult patients should receive 3 further doses of 900mg of Eculizumab at weekly intervals. A dose of 1200mg is administered one week after the final dose of 900mg and every 2 weeks thereafter The dose and dosing schedule should be adjusted for body weight in children as per paediatric dosing schedule.

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.

 

Post-Transplant TMA

Thrombotic microangiopathy occurring in the post-transplant period can be due to several factors including acute antibody mediated rejection and calcineurin inhibitor toxicity. Currently Eculizumab is not licenced for treatment of secondary TMAs. However, there is evidence that some cases of post-transplant TMA may be due to defective complement regulation. These patients may therefore benefit from treatment with Eculizumab. We are happy to discuss any patient with evidence of a post-transplant TMA and can arrange testing for complement activation and for abnormalities in complement regulation.