Cellular Involvement Rather Than Humoral Characteristics Predict Renal Graft Dysfunction 1 Year After Antibody Mediated Rejection.

Abstract

Antibody-mediated rejection (AMR) after renal transplantation is frequently resistant to conventional anti-rejection therapy and often results in graft dysfunction (Gdys); however, risk factors for Gdys following AMR remain poorly defined. The purpose of this study was to identify predictors of Gdys, defined as graft loss or GFR reduction by ≥50%, at 1 year post-AMR treatment. Kidney transplant recipients treated for biopsy-proven AMR (n=49) were reviewed. Factors approaching significance (p<0.2) in the univariate analysis were included in a multivariate logistic regression backward elimination model to identify independent risk factors for Gdys. Mean time to AMR diagnosis following transplant was 14.5 months. Gdys at 1 year was seen in 22 (45%) patients, with graft loss occurring in 9 patients. Baseline characteristics including age, gender, race, donor type, sensitization, and induction type were similar between groups. The most common anti-humoral therapies administered were IVIG (n=46) and plasma exchange (n=39), with rituximab (n=22) or bortezomib (n=8) given in certain cases; ATG was added to anti-humoral therapies for mixed antibody-cellular rejections. Factors associated with Gdys by univariate analysis were prior cellular rejection, mixed rejection, and plasma cell infiltrates, while bortezomib use was associated with function at 1 year. In contrast, Gdys was not associated with DSA presence, number of antibody specificities, DSA strength, presence of capillaritis or glomerulitis, or other anti-humoral treatments. Multivariate analysis revealed mixed rejection as the only independent predictor of Gdys. Our data suggests that in renal transplantation, concurrent cellular rejection, rather than humoral characteristics, predicts poor graft outcomes at 1 year.Table: No Caption available.Table: No Caption available.