Background: Antibody mediated rejection (AMR) is associated with poor graft survival. Targeted treatment with bortezomib has been shown to reduce donor specific antibodies (DSA), but its impact on AMR clinical outcomes remains speculative. We investigated whether the addition of bortezomib to conventional therapy improves outcomes after AMR.

Methods: From 2009-2012, 20 kidney transplant patients were treated for biopsy proven AMR with bortezomib, steroids, plasmapheresis (PP), and intravenous immunoglobulin (IVIG). We compared the bortezomib group to a historical group with AMR (n=14) that did not receive bortezomib. Efficacy was evaluated comparing reduction in DSA (>50% decrease), graft function at 3 months, and allograft survival.

Results:

Baseline and treatment data are provided in Table 1. Table 2 shows clinical response. More patients in the bortezomib group had a significant reduction in Class I DSA (P=0.06). There was not a significant difference in reduction of Class II DSA between groups (29% vs. 40%, P=0.99). Three months post-therapy, serum creatinine (SCr) decreased significantly in the bortezomib group from 3.4 ± 2.6 to 2.1 ± 1 mg/dL (P=0.02) but not in the no-bortezomib group, 5 ±3.5 to 3.3 ±2.6 mg/dL (P=0.10). Three month SCr was lower in the bortezomib group but not statistically different (2.1±1 vs. 3.3±2.6 mg/dL, P=0.47). Graft survival was significantly better in the bortezomib group (P=0.04).

Conclusion:

The addition of bortezomib to PP and IVIG was associated with reduction in Class I DSA. Lower 3-month SCr and better graft survival may be attributed to the inclusion of patients with subclinical AMR in the bortezomib group. We hypothesize that early intervention of antibody mediated rejection in renal allografts may have a salutary effect on graft survival.

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