Treatment of Acute Antibody-Mediated Renal Allograft Rejection with Cyclophosphamide.

Background: Antibody-mediated rejection (ABMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated, whether cyclophosphamide combined with plasmapheresis (PPH) and intravenous immunoglobulins (IVIG) is an option for patients with ABMR. Methods: Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute ABMR with i.v. cyclophosphamide pulses (15mg/kg adapted to age and renal function) at 3-week intervals, PPH (6x), and high-dose IVIG (1.5g/kg). Treatment was completed after 6 cyclophosphamide pulses or in case of return to baseline serum creatinine together with reduction of donor-specific HLA antibodies (DSA) below 500 mean fluorescence intensity (MFI). Results: 11/13 patients completed treatment. Median follow-up was 18(12-44) months. At the end of follow-up graft survival was 77%(10/13). The 3 graft losses were caused by non-adherence and premature termination of treatment. Serum creatinine increased from 1.7+/-0.4mg/dL at 3 months before diagnosis to 3.7+/-2.4mg/dL at diagnosis (p=0.01), and decreased to 2.1+/-0.7mg/dL at 3 months after diagnosis (p=0.01). In 7/11(64%) patients, who completed treatment, DSA decreased, in 4/11(36%) DSA were below 500 MFI after treatment. Dose reductions had to be performed in 3/13 patients for leukopenia. We observed 14 hospitalizations in 9/13 patients. Conclusions: To our knowledge, this is the first systematic report on cyclophosphamide-based treatment of acute ABMR based on modern diagnostics. Treatment was effective and relatively safe. Future studies will show, whether cyclophosphamide proves to be a valuable alternative for the treatment of ABMR. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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