Eculizumab for Salvage Treatment of Refractory Antibody-Mediated Rejection in Kidney Transplant Patients: Case Reports B. Kocak, E. Arpali, E. Demiralp, B. Yelken, C. Karatas, S. Gorcin, N. Gorgulu, M. Uzunalan, A. Turkmen, and M. Kalayoglu ABSTRACT Antibody-mediated rejection (AMR) in a group of preoperatively desensitized patients may follow a dreadful course and result in loss of the transplanted kidney. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD 20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present two cases of acute-onset AMR in preoperatively desensitized patients. Eculizumab was used as a salvage agent in addition to conventional therapy. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss. A NTIBODY-MEDIATED REJECTION (AMR) in trans- plant recipients who have antibodies specific for donor HLA (DSA) may cause graft loss or result in decreased graft survival. 1 AMR following desensitization with plasma- pheresis (PP) and intravenous immunoglobulin (IVIg) for HLA- incompatible kidney transplantation is usually responsive to rein- itiation of PP/IVIg and anti-CD20 therapy. 2,3 However, in a group of patients the current protocols may not be enough to clean the burden of DSA, and severe allograft damage occurs dramatically. These severe cases can generally be defined by a rapid onset of renal dysfunction, oliguria, and a marked rise in DSA. 1 A humanized, anti-C5 monoclonal antibody, eculizumab, has been shown to be effective in the treatment of refractory atypical HUS and in the management of patients at high risk for AMR. 4–6 Here, we present two cases that were resistant to conventional therapy and eculizumab was given as a salvage treatment. CASE REPORTS Case 1 A 26-year-old woman with a history of previous living related renal transplant from her brother 2 years previously, which was lost secondary to AMR in the early postoperative period, was evaluated for a second living related kidney transplant from her father. Her cytotoxicity crossmatch (CDCXM) and flow cytometric crossmatch results were found to be negative. However, solid-phase immuno- assays (Luminex) revealed that the patient had DSA against donor’s HLA-B13 (MFI  7000). C1q assay was negative. The patient received five PP and IVIg (500 mg/kg) prior to transplant resulting in reduced DSA titers (MFI  3000). Thymoglobulin induction was used and maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetile, and prednisolone. The graft functioned immediately and her serum creatinine decreased to 1.52 mg/dL on postoperative day (POD) 2. Her serum creatinine level was increased to 2.1 mg/dL and the urine output decreased gradually on POD 3. Transplant kidney scan was unremarkable. DSA titers for HLA-B13 bumped to over 22,000 MFI. Bolus steroid treatment was started on POD 3 (500 mg/d, for 3 days). IVIg was started on POD 5 (500 mg/kg). The patient had throm- bocytopenia and decreasing hemoglobin levels and rising serum LDH levels, consistent with microangiopathic hemolysis. Thymo- globulin was stopped due to severe thrombocytopenia and a single dose of alemtuzumab was given. PP was reinitiated on POD 8. Transplant graft biopsy revealed AMR, Banf type III with severe glomerular and tubular necrosis, diffuse thrombotic microangiopa- thy, and diffuse necrotizing fibrinoid vasculitis. C4d staining was From the Istanbul Memorial Hospital, Department of Solid Organ Transplantation, Okmeydani/Istanbul, Turkey. Address reprint requests to Emre Arpali, Istanbul Memorial Hospital, Department of Solid Organ Transplantation, Piyalepasa Bulvari 34385 Okmeydani/Istanbul, Turkey. E-mail: arpemre@ gmail.com 0041-1345/13/$–see front matter © 2013 by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.transproceed.2013.02.062 360 Park Avenue South, New York, NY 10010-1710 1022 Transplantation Proceedings, 45, 1022–1025 (2013)