Pre-transplant donor-specific anti-human leukocyte antigen antibodies are associated with high risk of delayed graft function after renal transplantation

Sensitive screening methods have revealed that many patients have donor-specific human leucocyte antigen antibodies (DSAs) prior to transplantation, regardless of negative crossmatch results. The clinical significance of pre-transplant (pre-Tx) DSAs for early graft function has remained unclear. Our aim was to examine the association of DSAs with delayed graft function (DGF). Pre-Tx sera of 771 patients who received kidney transplants in our single-centre study were retrospectively screened. All transplantations were performed after negative complement-dependent cytotoxicity (CDC) crossmatch. DSAs were detected in 13% of the patients. The overall DGF rate in our study was 29%. Patients with DSAs had a higher incidence of DGF when compared with non-sensitized patients (48 and 26%, respectively; P < 0.0001). Third-party antibodies had no effect for DGF incidence (28%; P = 0.6098). The relative risk (RR) of DGF for patients with DSAs in the multivariate analysis was 2.039 (95% CI 1.246-3.335; P = 0.0046). Analyses of the cumulative mean fluorescent intensity (MFI) value of the DSAs revealed a rate of DGF more than two times higher in patients with a cumulative value of 3000-5000 MFI compared with a cumulative value of 1000-3000 (65 versus 31%; P = 0.0351). DSAs against any loci showed an elevated DGF incidence of 44-69% when compared with patients without DSA (27%). The risk of DGF is twice as high in patients having pre-formed DSAs. Pre-Tx DSAs is a modifiable risk factor that can be obviated with careful organ allocation relying on careful pre-Tx analysis of non-accepted mismatches determined with sensitive solid phase methods.