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Treatment of Acute Antibody-Mediated Renal Allograft Rejection With Cyclophosphamide

Waiser, Johannes MD1; Duerr, Michael MD1; Budde, Klemens MD1; Rudolph, Birgit MD2; Wu, Kaiyin MD1,2; Bachmann, Friederike MD1; Halleck, Fabian MD1; Schönemann, Constanze PhD3; Lachmann, Nils PhD3

doi: 10.1097/TP.0000000000001617
Original Clinical Science—General

Background Antibody-mediated rejection (AMR) 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 and intravenous immunoglobulins is an option for patients with AMR.

Methods Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute AMR with intravenous cyclophosphamide pulses (15 mg/kg adapted to age and renal function) at 3-week intervals, PPH (6×), and high-dose intravenous immunoglobulin (1.5 g/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.

Results Eleven of 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 at least in part by nonadherence and premature termination of treatment. Serum creatinine increased from 1.7±0.4 mg/dL at 3 months before diagnosis to 3.7±2.4 mg/dL at diagnosis (P = 0.01), and decreased to 2.1 ± 0.7 mg/dL at 3 months after diagnosis (P = 0.01). In 7 (64%) of 11 patients, who completed treatment, DSA decreased, in 4 (36%) of 11 DSA were below 500 mean fluorescence intensity after treatment. Dose reductions had to be performed in 3 of 13 patients for leukopenia. We observed 14 hospitalizations in 9 of 13 patients.

Conclusions To our knowledge, this is the first systematic report on cyclophosphamide-based treatment of acute AMR 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 AMR.

The authors first report on 13 kidney transplant recipients with antibody-mediated rejection treated with cyclophosphamide, plasma exchange and IVIg with a mean follow up of 18 months with a decrease in serum creatinine, in DSA MFI and a small incidence of neutropenia.

1 Medizinische Klinik mit Schwerpunkt Nephrologie, Charité Universitätsmedizin Berlin, Berlin, Germany.

2 Institut für Pathologie, Charité Universitätsmedizin Berlin, Berlin, Germany.

3 HLA-Labor, Zentrum für Tumormedizin, Charité Universitätsmedizin, Berlin, Germany.

Received 22 July 2016. Revision received 14 November 2016.

Accepted 2 December 2016.

J.W. and M.D. contributed equally to the study.

The authors declare no funding or conflicts of interest.

J.W., M.D., N.L. participated in the conception, data acquisition and analysis, preparation and writing of the article. K.B., C.S. participated in the conception, review and proofreading of the article. B.R., K.W., F.B., F.H. participated in the data acquisition and analysis, review and proofreading of the article.

Correspondence: Johannes Waiser, MD, Medizinische Klinik mit Schwerpunkt Nephrologie, Charité Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany. (johannes.waiser@charite.de).

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