Background Eculizumab (EZB) is approved by NHSE in the UK for prevention and managment of recurrent aHUS after kidney transplantation. Purpose We report aggressive recurrence of aHUS post transplant despite EZB and report on a collaborative approach using combination therapy to manage the disease. Report A 58 year old female was called for deceased donor transplantation. She had presented 3 years earlier following viral illness with aHUS with Factor H mutation. Plasma exchange (PLEX) restored haematological parameters but the patient was left dialysis dependent. She received a kidney from a young DCD donor with HLA MM III. EZB 900mg was given preimplantation with basiliximab, tacrolimus, mycophenolate and prednisolone. Delayed graft function occurred and by day 3 platelets and haemoglobin had fallen to 91×10⁹/l and 95g/l respectively with LDH 1500. Fragmentation on blood film was only seen on day 3 and a second dose of EZB 900mg given. Transplant biopsy showed florid TMA with C3 deposition and negative C4d. HLA antibody screen pre and post-transplant was negative. Serum C3 was reduced but CH100 / AP100 showed no lysis zones or activity suggesting effective terminal complement pathway blockade by EZB. Platelets continued to fall with rising LDH and oliguria. Daily centrifugal PLEX was commenced (day 6) (platelets 20) using initially Octaplas then FFP (to provide increased active Factor I and H). ADAMTS13 was 32% and C5 polymorphism conferring EZB resistance excluded. EZB was administered after each PEX. Haematological parameters improved over the first week with subsequent increase in urine output. PEX was discontinued after 15 daily sessions and dialysis discontinued on post-transplant day 23. EZB 1200mg weekly then 1500mg two weekly from week 8 was administered. Repeat biopsy (2 months) showed 40 healthy glomeruli but fibromyxoid changes in 2 vessels. Creatinine at 10 weeks post transplant was 296umol/l. Discussion Aggressive early recurrence of aHUS may occur despite EZB and apparent complement pathway blockade (AP100/CH100). Improved understanding of possible recurrence related factors such as ischaemia-reperfusion injury is needed to risk stratify and identify individuals at risk who may require combination therapies.

CITATION INFORMATION: Morton M, Chinnadurai R, Ahmed S, Sharma A, Dutt T, Bhutani S, Denley H, Augustine T, Goodship T, Sheerin N, Picton M. Management of Recurrent aHUS After Adult Kidney transplantation Despite Eculizumab Prophylaxis. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress