P-155

Treatment of de novo atypical HUS post kidney pancreas transplant with eculizumab

C. Wilson¹, B. Jaques¹, J. Shaw², D. Talbot¹, D. Manas¹, T. Goodship², N. Sheerin², S. White^1
1 Freeman Hospital, Institute of Transplantation, Newcastle, U.K.; ² Institute of Cellular Medicine, Newcastle University, Newcastle, U.K.

Introduction: Post transplant microangiopathy (atypical Haemolytic Uraemic Syndrome, aHUS) has been associated with a number of initiating insults including calcineurin inhibitors, antibody mediated rejection and ischaemia. The pathogenesis is associated with a failure in local complement regulation. Conversion to sirolimus (Rapamycin®, Wyeth) and plasmapheresis (PEX) have been the mainstays of therapy. Even with this, a high percentage of cases fail to achieve remission and lose their grafts.

Methods and Results: We recently treated a 46 yr old male SPK recipient diagnosed with aHUS on renal biopsy 3 weeks after transplantation. Post op he developed a number of complications including antibody mediated vascular rejection, pyrexia of unknown origin and tacrolimus toxicity precipitated by the use of fluconazole. To treat the thromobotic microangiopathy he was commenced on PEX therapy and switched from tacrolimus to sirolimus. However, after 18 cycles of PEX, he remained dialysis dependent and was started on eculizumab (Soliris ®, Alexion). His platelet count responded to the first infusion of eculizumab and, after only 4 infusions, his renal function had improved and stabilised (6 month follow up) at a predicted GFR of around 40 ml/min/1.73m2. Subsequent genetic testing has failed to find a complement factor mutation.

Conclusion: Eculizumab therapy appears to be effective and can induce persistent remission in cases of aHUS refractory to PEX.

P-155

Treatment of de novo atypical HUS post kidney pancreas transplant with eculizumab

C. Wilson¹, B. Jaques¹, J. Shaw², D. Talbot¹, D. Manas¹, T. Goodship², N. Sheerin², S. White^1
1 Freeman Hospital, Institute of Transplantation, Newcastle, U.K.; ² Institute of Cellular Medicine, Newcastle University, Newcastle, U.K.

Introduction: Post transplant microangiopathy (atypical Haemolytic Uraemic Syndrome, aHUS) has been associated with a number of initiating insults including calcineurin inhibitors, antibody mediated rejection and ischaemia. The pathogenesis is associated with a failure in local complement regulation. Conversion to sirolimus (Rapamycin®, Wyeth) and plasmapheresis (PEX) have been the mainstays of therapy. Even with this, a high percentage of cases fail to achieve remission and lose their grafts.

Methods and Results: We recently treated a 46 yr old male SPK recipient diagnosed with aHUS on renal biopsy 3 weeks after transplantation. Post op he developed a number of complications including antibody mediated vascular rejection, pyrexia of unknown origin and tacrolimus toxicity precipitated by the use of fluconazole. To treat the thromobotic microangiopathy he was commenced on PEX therapy and switched from tacrolimus to sirolimus. However, after 18 cycles of PEX, he remained dialysis dependent and was started on eculizumab (Soliris ®, Alexion). His platelet count responded to the first infusion of eculizumab and, after only 4 infusions, his renal function had improved and stabilised (6 month follow up) at a predicted GFR of around 40 ml/min/1.73m2. Subsequent genetic testing has failed to find a complement factor mutation.

Conclusion: Eculizumab therapy appears to be effective and can induce persistent remission in cases of aHUS refractory to PEX.