Background:The development of donor-specific antibodies (DSAs) is associated with chronic rejection, inferior graft survival, and poor quality of life. Recent HLA DR/DQ-eplets matching between donor and recipient are better predictors for the development of de novo DSAs and graft outcome. Limited data on the association between proper tacrolimus (Tac) level and HLA class II eplets-mismatch loads on kidney graft outcomes are available. Methods: We examined 194 kidney transplant recipients with molecular HLA typing by Luminex by July 2022. High total eplets MM (≥17), high all Abv eplets MM (≥7), high coefficient variability (CV, ≥17%), and high intrapatient variability (IPV, ≥13%) were defined, respectively. The purpose of our study was to evaluate whether different types of Tac levels (a nadir level, mean trough level, CV, and IPV) are associated with the development of de novo DSA and poor graft outcomes Results: The low nadir of Tac trough level (<6 ng/mL) is a risk factor for the development of de novo DR-DSA and DQ-DSA, respectively. Four different Tac tests; the low nadir of Tac level (<6 ng/mL), low mean Tac level (<7 ng/mL), high CV (≥17%), and high IPV (≥13%), were significantly associated with inferior graft survival. High low IPV and low total eplets MM showed the lowest death censored graft survival rate compared with the low/low group, as a reference. Independent predictors of graft failure on multivariate analysis were chronic ABMR, and the low nadir of Tac trough level (<6 ng/mL). Conclusions: Our study demonstrated that combined high DQ/DR-eplets mismatch with high IPV and/or low Tac trough levels were significantly associated with poor graft outcomes, respectively. We also tested four different Tac levels, which were related to inferior graft survival, but high eplets MM was not associated. Our study needs to verify whether intensifying immunosuppression improves graft outcomes among patients who have high DR, DQ-eplets mismatch.

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