Impact on mid-term kidney graft outcomes of pretransplant anti-HLA antibodies detected by solid-phase assays: Do donor-specific antibodies tell the whole story?

The detrimental impact of preformed anti-HLA donor-specific antibodies (DSA) is well defined, contrarily to non-donor-specific antibodies (NDSA). We sought to evaluate their clinical impact in a cohort of 724 kidney graft recipients in whom anti-HLA antibodies were thoroughly screened and identified in pre-transplant sera by solid-phase assays. NDSA or DSA were detected in 100 (13.8%) and 47 (6.5%) recipients respectively, while 577 (79.7%) were non-allosensitized (NaS). Incidence of antibody-mediated rejection at 1-year was 0.7%, 4.0% and 25.5% in NaS, NDSA and DSA patients, respectively (NaS vs. NDSA P = 0.004; NaS vs. DSA P < 0.001; NDSA vs. DSA P < 0.001). Graft survival was lowest in DSA (78.7%), followed by NDSA (88.0%) and NaS (93.8%) recipients (NaS vs. NDSA P = 0.015; NaS vs. DSA P < 0.001; NDSA vs. DSA P = 0.378). Multivariable competing risk analysis confirmed both NDSA (sHR = 2.19; P = 0.025) and DSA (sHR = 2.87; P = 0.012) as significant predictors of graft failure. The negative effect of NDSA and DSA on graft survival was significant in patients receiving no induction (P = 0.019) or an anti-IL-2 receptor antibody (P < 0.001), but not in those receiving anti-thymocyte globulin (P = 0.852). The recognition of the immunological risk associated with preformed DSA but also NDSA have important implications in patients' risk stratification, and may impact clinical decisions at transplant.