Diagnosis and treatment of acute antibody-mediated rejection in renal transplant: the role of C4d and donor-specific antibody identification

Objective: To evaluate the incidence of antibody-mediated rejection after the C4d and donor specific antibody detection was provided by Luminex in renal transplantation biopsies; to compare acute antibody-mediated rejection characteristics as related to acute cellular rejection; to evaluate the impact on the incidence of acute antibody mediated rejection after the utilization of cross match test by flux cytometry and the detection of pre-transplantation donor specific antibody in patients with previous history of exposition to alloantigens. Methods: One hundred twenty-four renal transplanted patients were evaluated through the detection of C4d in early biopsies of those presenting graft dysfunction and the detection of antibody against donor when C4d was positive. The acute antibody mediated rejection was treated by plasmapheresis and intravenous immunoglobulin. Results: The incidence of acute rejection was 18.8%, being the acute cellular rejection 14.9% and acute antibody mediated rejection 6.6%. When both were compared, the acute antibody-mediated rejection were earlier than the acute cellular rejection (12.5 versus 59.9 days, p = NS), being more frequent in female patients (75 versus 29%, p = 0.05), with deceased donors (75 versus 33%, p = 0.09), with higher dialysis time (87.7 versus 47.4, p = 0.03), greater number of transfusion episodes (4.6 versus 1.4, p = 0.02), greater panel reaction activity (28.0 versus 4.8, p = 0.03) and more frequently in re-transplanted patients (50 versus 5.6%, p = 0.02). Delayed graft function was more frequent in antibody mediated rejection (100 versus 50%, p = 0.02). All patients with acute cellular rejection reversed graft function after treatment, with 100% graft survival after one year. Among patients with acute antibody-mediated rejection, the treatment with plasmapheresis and immunoglobulin was efficient in reducing the titers of donor specific antibody (2605 versus 202 mfi, p < 0.001), but 3/8 of patients evolved to graft loss, making graft survival of 62.5% (p < 0.001). Conclusions: The routine use of detecting C4d and donor specific antibody increased the incidence of acute rejection. Acute antibody-mediated rejection presented clinical profile and therapeutic response different from acute cellular rejection, identifying a worse prognosis as well as therapeutic success. Objetivo: Avaliar a incidencia da rejeicao mediada por anticorpo depois de instituida a pesquisa de C4d em biopsias de rim transplantado e pesquisa de anticorpo especifico de doador pelo Luminex; comparar as caracteristicas da rejeicao aguda mediada por anticorpo em relacao a rejeicao aguda celular; avaliar o impacto na incidencia de rejeicao aguda mediada por anticorpo apos utilizar a prova cruzada por citometria de fluxo e pesquisa de anticorpo especifico de doador pre-transplante em pacientes com historico de exposicao previa a aloantigenos. Metodos: Foram avaliados 124 pacientes transplantados renais, com pesquisa de C4d em biopsias precoces em pacientes com disfuncao do enxerto e pesquisa de anticorpo contra o doador quando o C4d foi positivo. A rejeicao aguda mediada por anticorpo foi tratada com plasmaferese e imunoglobulina intravenosa. Resultados: Foi encontrada uma incidencia de rejeicao aguda de 18,8%, com frequencia de episodios de rejeicao aguda celular de 14,9% e de rejeicao aguda mediada por anticorpo de 6.6%. Quando comparados com rejeicao aguda celular, os episodios de rejeicao aguda mediada por anticorpo foram mais precoces (12,5 versus 59,9 dias, p = NS), sendo mais frequentes em pacientes femininas (75% versus 29%, p = 0,05), com doadores falecidos (75% versus 33%, p = 0.09), com maior tempo de dialise (87,7 versus 47,4, p = 0,03), maior numero de transfusoes (4,6 versus 1,4, p = 0,02), maior atividade contra painel (28,0 versus 4,8, p = 0,03) e mais frequentemente retransplantados (50 versus 5,6%, p = 0,02). Funcao retardada do enxerto foi mais frequente nos pacientes com rejeicao aguda mediada por anticorpo (100 versus 50%, p = 0,02). Todos os pacientes com rejeicao aguda celular reverteram a funcao do enxerto apos o tratamento, com sobrevida do enxerto, em um ano, de 100%. Entre os pacientes com rejeicao aguda mediada por anticorpo, o tratamento com plasmaferese e imunoglobulina foi eficiente em reduzir os titulos de anticorpo especifico de doador (2.605 versus 202 mpi, p < 0,001), mas 3/8 pacientes evoluiram para perda do enxerto, conferindo sobrevida do enxerto de 62,5% (p < 0,001). Conclusoes: O uso rotineiro da pesquisa de C4d e anticorpo doador especifico aumentou a incidencia de rejeicao aguda. A rejeicao aguda mediada por anticorpo apresentou perfil clinico e resposta terapeutica diferentes da rejeicao aguda celular, conferindo-lhe pior prognostico e pior resposta terapeutica.