*Purpose: Prior studies in kidney transplant recipients (KTR) have demonstrated that lower tacrolimus (TAC) exposure during the first week is associated with an increased incidence of biopsy-proven acute rejection (BPAR), even in the setting of lymphocyte-depleting therapy, such as rabbit antithymocyte globulin. This has not been evaluated in KTR receiving alemtuzumab induction.

*Methods: This was a single-center, retrospective study of adult KTR from 1/2015 to 12/2017 who received alemtuzumab induction and TAC-based maintenance immunosuppression. Patients were divided into two groups according to whether TAC was therapeutic at postoperative day (POD) 7 (>8 ng/mL and <8 ng/mL). The primary outcome was the incidence of BPAR at 12 months between groups. The incidence of antibody-mediated rejection (AMR), allograft function according to estimated glomerular filtration rate (eGFR), delayed graft function (DGF), and patient and graft survival were analyzed.

*Results: Of the 400 patients included, 158 (40%) had a TAC trough >8 ng/mL by POD7. The 242 (60%) patients in the TAC <8 ng/mL group contained a significantly higher proportion of black patients, recipients of deceased donor allografts, and were more likely to be on prednisone at discharge. Overall, 31 (7.8%) experienced BPAR at 12 months, with a significantly higher incidence in the TAC <8 ng/mL group compared to the >8 ng/mL group (9.9% vs 4.4%, p=0.045). This group also had a significantly higher rate of AMR (4.1% vs. 0%, p<0.007) and a 2-fold increase in DGF (22.3% vs 11.4%, p=0.005) compared to the >8 ng/mL. There was no difference in death or graft loss at 12 months, and the only difference in eGFR was at the time of discharge.

*Conclusions: Failure to reach therapeutic tacrolimus troughs within 7 days post-transplant, even in the setting of alemtuzumab induction, was associated with higher BPAR rates.

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