*Purpose: High variability in tacrolimus as assessed by tacrolimus coefficient of variability (TCV) in trough levels of kidney transplant recipients (KTRs) has been associated with an increased risk of rejection, graft loss, and de novo donor specific antibody (dnDSA) development. Limited data exists assessing TCV in patients receiving alemtuzumab induction. This study describes the impact of intrapatient tacrolimus variability in KTR on dnDSA development, infectious complications, and graft outcomes up to 3 years post-transplant under alemtuzumab induction.

*Methods: All KTRs from 1/1/2013-12/31/2017 receiving alemtuzumab induction and tacrolimus-based immunosuppression at a single center were included. Pediatric, prior transplant, ABO incompatible, and dual organ KTRs were excluded. Most patients received mycophenolate de novo with early steroid withdrawal. TCV was calculated at 0-3 and 3-12 months to align with protocol trough goal changes. Patients were categorized into high TCV, defined as greater than 30%, or low TCV, less than 30% in concordance with previous studies. Differences in mortality, dnDSA, BPAR, BK and CMV viremia, and glomerular filtration rate (GFR) were assessed between high and low TCV groups up to 3 years post-transplant.

*Results: 214 KTRs were included (Table 1). The median TCV from 0-3 and 3-12 months was 28.1% and 25.8%, respectively. KTRs with high TCV in the first year had more BPAR (14.3% vs. 5.7%, p=0.048) and decreased GFR at 3 and 12 months (67.7 ± 35.48 vs. 0.7 ± 29.3, p=0.010 and 70.9 ± 35.4 vs. 83.3 ± 30.2, p=0.015, respectively). High TCV in the first year was also associated with increased incidence of CMV viremia (19.6% vs. 9.3% p=0.046) and a numerically higher incidence of BK viremia (32.1% vs. 21.4%, p=0.14) and BK nephropathy (16.1% vs. 7.9%, p=0.115) up to 3 years, although not significant. Fifty-five (27%) KTRs developed dnDSA at a median time of 183 days. No difference in mortality (3.6% vs. 2.9%, p=0.793) or dnDSA development (25.7% vs. 25.0%, p=0.24) at 3 years was seen between high and low TCV.

*Conclusions: High TCV in alemtuzumab-induced KTRs was associated with poorer graft function and increased BPAR, as well as an increased CMV viremia rate and may be associated with increased risk of BK viremia and nephropathy. No difference in survival or dnDSA development was seen. Further research is needed to determine the clinical utility of prospective TCV monitoring in modifying clinical outcomes.

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