Diagnosis and Treatment of Acute Humoral Kidney Allograft Rejection A.M. Gomes, S. Pedroso, L.S. Martins, J. Malheiro, J.R. Viscayno, J. Santos, L. Dias, A.C. Henriques, A.M. Sarmento, and A. Cabrita ABSTRACT Acute humoral rejection (AHR) is a severe form of rejection associated with poor graft survival. Prompt diagnosis and rapid institution of therapy are crucial to improve the prognosis. A therapeutic approach based on plasmapheresis, intravenous imunoglobulin, and rituximab seems to be effective in refractory cases. Herein we have described our experience with 11 patients with biopsy-proven AHR who were treated between January 2005 and June 2008. Seven of these patients had panel reactive antibodies titers more than 50%. The diagnosis was based on Banff 2001 criteria; treatment consisted of a combination of plasmapheresis and intravenous immunoglobulin. Four refractory cases were also treated with a single dose of rituximab. One graft was lost due to thrombosis. All other patients recovered graft function with an average creatinine level of 1.6 mg/dL at 8.6  2.7 months of follow-up. O VER the last decade, acute humoral rejection (AHR) has been recognized as a distinct important mechanism of acute rejection. AHR occurs when alloantibodies attach to endothelial alloantigens, triggering the complement cascade and inducing capillary injury. The main alloantibodies are directed against major histocompatibility complex (MHC) molecules, also known as the human leukocyte antigens (HLA). 1–4 Recently, the development of immunopathologic staining for C4d, a marker of alloantibody-triggered com- plement activation has improved the diagnosis of AHR. Also, a group of high-risk patients has been identified. HLA sensitization results from exposure to various HLA antigens via prior transplantation, blood transfusions, or pregnancy. 1–3,5 The management of AHR is based on alloantibody removal and effective control of their produc- tion. Various therapeutic strategies have been used. 6 In the absence of data from randomized clinical trials, treatment relies on combinations of plasmapheresis (PP) or immuno- adsorption (IA) and intravenous immunoglobulin (IVIg), along with intense immunosuppression (tacrolimus and mycophenolate mofetil) with or without T-cell– depleting antibodies. 1,6 –9 In refractory patients, Rituximab (Rtx), a monoclonal anti-CD 20 antibody, has been increasingly used. 3,9,10 Fortunately, the incidence of AHR is low, ranging from 1.8%–3.2% but can result in 27%– 40% of grafts losses within the first year. 9,11,12 Herein we have described our experience with 11 patients who displayed biopsy-proven AHR between January 2005 and June 2008. PATIENTS AND METHODS We retrospectively reviewed all 292 renal transplantations at our center since C4d staining became available (January 2005), includ- ing 11 (3.7%) cases of AHR (Table 1). All cases occurred among deceased donor kidney transplants except patient number 2 who received a simultaneous renal-pancreas transplant. In all patients, baseline induction immunosuppression included tacrolimus (target blood levels of 12–15 ng/mL), mycophenolate mofetil (1 g twice a day), and steroids: intravenous methylprednisolone 500 mg at the time of transplantation times 3 and then prednisolone tapered to an oral dose of 5 mg daily at 6 months there after. Seven patients also received polyclonal antilymphocyte antibodies (antithymocyte globulin [ATG]; 3–5 mg/kg) over 10 consecutive days and 4 patients, daclizumab (2 times 2 mg/kg) for induction therapy. Biopsy was performed in cases of acute allograft dysfunction (an increase of more than 30% of plasma creatinine from baseline) or of delayed allograft function (requirement for dialysis in the first 7 days posttransplantation). Histological evaluation was made on formalin-fixed paraffin sections stained with hematoxylin and eosin, periodic acid-Schiff, methenamine-silver, and Masson trichrome stains. Polyclonal anti-C4d antibody (Quidel Corporation, San From the Nephrology Department (A.M.G.), Centro Hospitalar Vila Nova Gaia/Espinho, Gaia, Nephrology and Transplant De- partments (S.P., L.S.M., J.M., J.S., L.D., A.C.H., A.M.S., A.C.), and Pathology Department (J.R.V.), Hospital Geral de Santo António, Porto, Portugal. Address reprint requests to Dr Ana Marta Gomes, Nephrology Department, Centro Hospitalar Vila Nova Gaia/Espinho, Rua Conceição Fernandes, 3343-502 Vila Nova de Gaia, Gaia, Por- tugal. E-mail: ampgomes@gmail.com © 2009 by Elsevier Inc. All rights reserved. 0041-1345/09/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2009.01.062 Transplantation Proceedings, 41, 855– 858 (2009) 855