*Purpose: In this study, we aimed to identify the risk factors contributing to the development of donor-specific anti-HLA antibody (DSA) during long-term follow-up of patients post renal transplantation.

*Methods: Among patients who underwent renal transplantation since 2001, 245 patients who underwent anti-HLA antibody testing from 2018 to 2020 were evaluated. LAB Screen PRA® and SingleAntigen® were used to conduct the antibody test, and de novo DSA was determined based on the donor and recipient HLA alleles. The average, CV, and minimum outpatient tacrolimus (Tac) trough values within 1 year, 3 years, and 5 years before conducting the DSA test were calculated and statistically analyzed.

*Results: There were 21 dnDSA-positive individuals, and antibody specificities were 5, 1, 1, 3, 13, and 0 at the A, B, Cw, DR, DQ, and DP loci, respectively. The cumulative incidence of dnDSA was 1.0, 1.5, 3.5, 9.4, and 22.3% in 3, 5, 7, 10, and 15 years, respectively, thereby exhibiting an increase in the positive rate after the 7th year. Upon comparing the Tac trough value parameters and dnDSA production, the mean value within 1 year, 3 years, and 5 years was found to be significantly lower in the dnDSA positive group than in the negative group. No statistical difference was observed in comparison with the CV value and personal minimum value.

*Conclusions: The frequency of dnDSA occurrence and characteristics of high DQ antibody were the same as reported previously. Additionally, we confirmed that the risk of dnDSA production in the long-term follow-up patients with renal transplantation may be related to the difference in the Tac blood concentration of control.

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