Although HLA donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR), HLA incompatible (HLAi) transplants may be inevitable within highly sensitized patients. As HLA antibodies recognize epitopes, structurally defined by small polymorphic amino acid sequences named eplets, the aim of this study was to assess AMR risk due to donor-specific eplet (DSE) load in 60 HLAi kidney transplanted patients. HLA intermediate resolution typing was performed for HLA-A, -B, -C and -DRB1 loci and four-digit typing assigned for HLA-A, -B, -C, DRB1/3/4/5 and -DQA1/B1 based on population a frequencies databases and linkage disequilibrium. Pre-transplant HLA antibodies were determined using LabScreen single antigen beads for HLA class I and class II IgG and C1q (One Lambda, Inc) and antibody-verified DSE load assessed with HLAMatchmaker (version 2). AMR was reported in 18 (30.0%) patients and preformed HLA class I and II DSA were identified in 49 (80.0%) and 33 (55.0%) recipients, respectively. Patients with AMR had higher MFIsum (18149 vs 6665; p<0.001), DSE-II (8.9 vs 3.7; p=0.010), DSE-I+II (4.9 vs 1.5; p=0.010) and DSE-I+II-C1q (0.12 vs 1.78; p=0.007) when compared with no AMR. ROC analysis was performed to determine the predictive ability of MFIsum, DSE-I, DSE-II, IgG and C1q, for AMR occurrence. MFIsum higher than 17k (AUC=0.798, NPV=87.2%, PPV=65.0%, ACC=79.7%, p<0.001), DSE-II-IgG>1 (AUC=0.705, NPV=83.3%, PPV=44.8%, ACC=64.4%, p=0.013), DSE-I+II-IgG>8 (AUC=0.718, NPV=80.4%, PPV=69.2%, ACC=78.0%, p=0.008) and DSE-I+II-C1q>1 (AUC=0.638, NPV=76.0%, PPV=66.7%, ACC=74.6%, p=0.095) were significant predictors of AMR, while DSE-I-IgG, DSE-I-C1q and DSE-II-C1q alone were not. Also, MFIsum (OR=12.63; p<0.001), DSE-II-IgG (OR=4.06; p=0.023), DSE-I+II-IgG (OR=9.25; p=0.002) and DSE-I+II-C1q (OR=6.33; p=0.018) were significant risk factors for AMR. Pre-transplant DSE IgG load for HLA class I and both class I and II, but also C1q for HLA class I and II, can to be an additional reliable marker, alongside with MFIsum value, for AMR prediction in HLAi kidney transplantation.