Early Antibody Mediated Rejection in HLA Antibody Incompatible Kidney Transplantation – A Treatable Condition Without Heavy Induction Immunosuppression

S. Daga,^1,2 N. Krishnan,¹ D. Lowe,³ F. Lam,¹ C. Imray,^1,2 H. Kashi,¹ L. Tan,¹ D. Briggs,³ R. Higgins.^1,2

¹Renal Department, University Hospital, Coventry, United Kingdom
²Warwick Medical School, University of Warwick, Coventry, United Kingdom
³H&I Department, NHSBT, Birmingham, United Kingdom.

Meeting: 2015 American Transplant Congress

Abstract number: A294

Keywords: HLA antibodies, Kidney transplantation, Rejection, Vaccination

Session Information

Session Name: Poster Session A: Late Breaking

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

Transplantation across preformed donor specific HLA antibodies (DSA) not only carries a risk of early acute antibody mediated rejection (AMR) and graft loss, but also increased mortality from excessive immunosuppression. We reviewed our strategy of diagnosis and treatment of early AMR against clinical outcomes at 3 months post transplant.

Between 2003 and 2014, 120 patients received transplantation across a preformed DSA barrier. Six also had ABO incompatibility. Routine immunosuppression was with basiliximab, tacrolimus, mycophenolate and prednisolone (BTMP). Cytotoxic crossmatching (CDC)without anti-human globulin enhancement, Flow cytometric cross match (FC)and DSA using microbead assays were performed.

Of the 120 cases, 54 (45%) had AMR within the first 30 days post-transplant. Of the 66 cases with no rejection, 9 (14%) received ATG or alemtuzumab on demand for delayed graft function and a suspicion of possible AMR, not subsequently confirmed. 15/25 (60%) of transplants with +ve pretreatment CDC had AMR, compared with 32/61 (52%) -ve CDC but +ve FC, and 7/35 (20%) with DSA but –ve CDC and –ve FC. Rejection was sufficiently severe to require dialysis therapy in 7/15 (47%) +ve CDC cases, and 11/39 (28%) –ve CDC.

In –ve CDC cases, reversal of AMR at 3 months was achieved in 39/39 (100%), compared with 12/15 (80%) with +ve CDC (ie 3/15 (20%) early graft loss). Treatment of AMR included combinations of ATG (26 cases), OKT3 (17), plasmapheresis (18), IVIg (6), others (5).Splenectomy or bortezomib were not used. Successful outcome at 3 months was associated with either DSA levels that returned to the –ve CDC baseline post-transplant, or rapidly rising DSA levels which then predictably fell to low levels soon after.

Six patients died in the first 3 months post transplant; 2/57 (3.5%) in patients who did not receive escalation of therapy over BTMP, 4/63 (6%) after escalation.

In summary, early acute AMR can be successfully treated without routine induction therapy above BTMP with a -ve pre treatment CDC crossmatch, using timely escalation of immunosuppression and prediction of changes in DSA levels. This strategy may be associated with reduced mortality. These findings should be confirmed in larger studies.

To cite this abstract in AMA style:

Daga S, Krishnan N, Lowe D, Lam F, Imray C, Kashi H, Tan L, Briggs D, Higgins R. Early Antibody Mediated Rejection in HLA Antibody Incompatible Kidney Transplantation – A Treatable Condition Without Heavy Induction Immunosuppression [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/early-antibody-mediated-rejection-in-hla-antibody-incompatible-kidney-transplantation-a-treatable-condition-without-heavy-induction-immunosuppression/. Accessed May 21, 2025.

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