Pretransplant Donor-Specific and Non-Specific Immune Parameters Associated With Early Acute Rejection

Abstract

New immunosuppression protocols have resulted in decreased rates of biopsy-proven acute rejection; however, it is unclear whether recipients without biopsy-proven acute rejection are still at risk for immune complication and chronic allograft dysfunction. The aim of our studies was to determine whether pretransplant immune parameters were associated with posttransplant early acute rejection, unstable creatinine courses, and poor graft outcome. Immune parameters, including human leukocyte antigen (HLA) mismatch, HLA-specific antibodies, global CD4+ cellular response as measured by intracellular adenosine triphosphate (iATP) synthesis, and IFN-gamma precursor frequencies to donor or third-party cells as measured by ELISPOT were determined for a total of 126 kidney recipients treated with a protocol, including rapid discontinuation of prednisone. The donor specific pretransplant parameters of HLA class I mismatches (P=0.04) and total HLA mismatches (P=0.04) with the donor as well as the pretransplant HLA-donor specific antibodies (P=0.002) were associated with biopsy-proven acute rejection. Higher pretransplant iATP levels, a donor nonspecific parameter, were found associated with biopsy proven acute rejection (P=0.04). Pretransplant iATP levels were significantly greater for recipients with early unstable creatinine levels (P=0.01). Recipients with a pretransplant iATP value greater than 375 ng/ml were 3.67 times more likely to experience acute rejection (P=0.03). Pretransplant assessment of donor specific and nonspecific immune parameters may identify recipients who can benefit from closer clinical and immunological surveillance to allow for tailored immunsuppression and selective intervention aimed at optimizing both short and long-term graft outcome.