Donor specific antibodies in the absence of rejection are not a risk factor for allograft failure

Abstract Introduction Donor-specific antibodies (DSA) are considered an important risk factor for graft injury and failure. However, there is limited information on long-term outcomes for kidney transplant recipients with positive DSA in the absence of rejection on biopsy. Methods We evaluated all patients at the University of Wisconsin who underwent a kidney allograft biopsy between 01/01/2013 and 12/31/2016. All patients with clinical indication or protocol biopsies which were negative for acute rejection and lacked significant acute pathological features were included in the study and divided into two groups based on DSA at the time of biopsy. There were a total of 1,102 kidney biopsies during the study period of which 587 fulfilled our selection criteria (DSA+, n=192, and DSA-, n=395). The incidence of subsequent rejection and death-censored graft failure (DCGF) were outcomes of interest. Results There was no difference in acute (i+t+v+C4d+ptc+g=0 in both groups) or chronic (ci+ct+cv+cg=2.4±2.2 vs. 2.7±2.4; cg=0.12±0.48 vs. 0.13±0.48) Banff scores in the index biopsy. Patients were followed for a mean of 33.1±16.8 months. Kaplan-Meier analyses demonstrated a higher incidence of DCGF in DSA- group (n=83) but this was not observed for subsequent rejection (n=76). In multivariate Cox regression analyses, the interval from transplant to biopsy, de novo DSA, younger age, and sum chronicity score remained independently associated with increased risk of subsequent rejection. Notably, there was no association between subsequent rejection or DSA (pre-transplant, de novo , persistant, Class I/II, MFI sum , or MFI max ) and graft failure. Conclusion This study suggests that in the absence of biopsy-proven rejection and acute inflammation, HLA DSA are not associated with increased risk of graft failure.