Hematocrit-adjusted tacrolimus levels are associated with acute kidney injury but not rejection early after liver transplantation.

Introduction: Tacrolimus (Tac) is highly bound to erythrocytes, with less than 1% present in the pharmacologically active unbound fraction. In anemia, whole-blood trough concentrations may underestimate effective exposure. Hematocrit (Hct) adjustment has been proposed but clinical outcome data are limited. Methods: We conducted a single-center retrospective cohort study of adult liver transplant recipients (2018 to 2022) to examine the relationship between Hct-adjusted Tac and early clinical outcomes. Tac troughs, Hct, and serum creatinine were collected for 90 days. Hct-adjusted Tac was calculated as (0.45 ÷ Hct) × total Tac. The difference between adjusted and measured Tac (delta Tac) was used to represent anemia-related underestimation and modeled as a time-varying covariate in Cox regression for acute kidney injury (AKI) and biopsy-proven T cell-mediated rejection (TCMR), adjusting for established risk factors. Results: Among 344 recipients (median age 59 years; 62% male), TCMR occurred in 15.7% and AKI in 69.8%. Delta Tac was not associated with TCMR (HR 0.93, 95% CI 0.77 to 1.14) but was associated with higher AKI hazard (HR 1.15 per ng/mL, 95% CI 1.08 to 1.24). Discussion: These findings suggest that divergence between Hct-adjusted and measured Tac is associated with increased AKI risk without a corresponding signal for rejection.