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

• Published in: Einstein (São Paulo, Brazil) Vol. 7; no. 4; pp. 427 - 435
• Main Authors: Lúcio Roberto Requião Moura, Margareth Afonso Torres, Eduardo José Tonato, Érika Ferraz de Arruda, Eric Roger Wroclawski, Maurício Fregonesi Rodrigues da Silva, Denise Maria Avancine Costa Malheiros, Marcelino de Souza Durão, Alvaro Pacheco-Silva
• Format: Journal Article
• Language: English
• Published: Instituto Israelita de Ensino e Pesquisa Albert Einstein 01.12.2009
• Subjects: Graft rejection/diagnosis; Graft rejection/therapy; HLA antigens; Kidney transplantation; Plasmapheresis
• ISSN: 1679-4508; 2317-6385

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. Rresults: 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). Cconclusions: 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.