LAUSR

BACKGROUND Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intra-patient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor-specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself. METHODS We analyzed the risk of de novo donor-specific antibodies, acute rejection, or death-censored graft loss by non dosed corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow up period of 4.1 years. RESULTS Patients with CV > 44.2% and TTR < 40% (high intra-patient variability and low time in therapeutic range) had a high risk of dnDSA (aOR 4.93, 95% CI 2.02-12.06, p<0.001) and death-censored graft loss by 5 years (aHR 4.00, 95% CI 1.31-12.24, p=0.015) when compared to patients with CV > 44.2% and TTR > 40% (high intra-patient variability and optimal time in therapeutic range), while the latter patients had similar risk to patients with CV < 44.2% (lower intra-patient variability). CONCLUSION These data suggest previously reported immunologic risk associated with high TAC intra-patient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non dose corrected TAC levels irrespective of reason or indication.