P240
ECULIZUMAB TREATMENT FOR SEVERE ACUTE ANTIBODY-MEDIATED REJECTION
(AMR) IN ABO INCOMPATIBLE RENAL TRANSPLANTATION
Arunachalam, C¹, Brown, A¹, Talbot, D¹, Sheerin, N¹, Baines, L¹, Carter, V2, Watson, E¹, Scuffell,C¹
¹Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, 2Histocompatibility and
Immunogenetics, NHSBT Newcastle.
Introduction
In ABO incompatible (ABOi) renal transplantation, AMR following desensitization protocols usually
responds to reinitiation of standard treatment of plasmapheresis (PP), intravenous immunoglobulin (IVIg)
and anti-CD20 therapy. However in certain cases of severe AMR characterised by a rapid decline in
renal function, oliguria and a concomitant marked rise in donor specific antibodies (DSA), these
treatments have been insufficient to rescue the organ.
Case report
We report a case of severe accelerated AMR treated with Eculizumab (anti-C5 monoclonal antibody). A
57 year old white male with primary disease of IgA nephropathy on haemodialysis was referred for renal
transplantation. Previous deceased donor renal transplant which lasted for 16 years was lost due to
recurrent disease. He received an ABO and HLA incompatible live donor renal transplant from his son
(blood group: donor A1+/recipient O+, 100 HLA mismatch and DSA to HLA-A24 (MFI 3500)). HLAA24 was not a repeat mismatch and he had moderate titres of anti-A antibodies (IgG 1:128, IgM 1:32).
Rituximab was administered 1 month before transplantation and Mycophenolate mofetil (MMF) with low
dose tacrolimus was begun when pre-operative IA was initiated. IA (Therasorb) was performed 8 times to
get the anti-A titres to IgG 1:8, IgM 1:2 on the day of transplantation. IVIg was given after the last IA
treatment. Flow and CDC cross matches were negative. Alemtuzumab induction was followed by
maintenance immunosuppression with tacrolimus, MMF and prednisolone.
The transplant functioned immediately and serum creatinine (sCr) dropped to 69μmol/L on post-operative
day (D) 5. He received 4 more sessions of IA (Therasorb) post-transplant. On D6, there was a sharp rise
in anti-A titres (IgG 1:32 and IgM 1:32). This was followed by worsening sCr (76 to 158μmol/L),
oliguria, drop in platelet count and a LDH rise. USS showed no obstruction with normal blood flow and
HLA-DSA remained low. A clinical diagnosis of acute AMR was made. In our experience with three
previous failed ABOi transplants, similar rises in antibody titres and deteriorating serum creatinine
despite PP/IVIg invariably led to graft thrombosis. This led to the decision to give Eculizumab in this
case and in addition he received IVIg and methylprednisolone.
Over the following 2 days, urine output improved but renal function continued to deteriorate and anti-A
titres continued to rise (both IgG & IgM 1:512). Transplant biopsy was not performed to avoid delay in
IA treatment. On D10, he was commenced on Glycosorb IA (selective removal of anti-A antibodies).
Glycosorb rather than PP was chosen to avoid Eculizumab removal. Absent CH50 levels throughout the
period he was receiving selective IA treatment confirmed that Eculizumab was not removed. On D13 sCr
peaked at 694 μmol/L and he needed haemodialysis. Antibody titres stayed high for 5 days even with IA
and after 7 sessions of Glycosorb the titres dropped (IgG 1: 16 and IgM 1:8). Graft function recovered
with normalization of the platelet count and LDH levels. He received 5 weekly infusions of Eculizumab
with no complications and renal function remains stable (sCr 95 μmol/L) at 2 months with minimal
proteinuria (urine PCR 23mg/mmol)
Conclusion:
In the case presented, presumed severe AMR
was successfully treated with a combination of
Eculizumab and selective antibody removal.
Given the very narrow period to intervene for
accelerated AMR, Eculizumab may offer a
graft-saving treatment option in isolated cases
refractory to standard treatment in ABOi
kidney transplantation.