2025 Southeastern Residency Conference

Title: Association Between Time-To-Therapeutic Tacrolimus Concentrations and Acute Rejection Following Heart and Kidney Transplant

Authors: Raymond Lin, Kwame Asare, Victoria Burnette

Introduction: Available evidence illustrates that greater time-in-therapeutic range tacrolimus therapy correlates with less acute rejection. There is minimal available evidence demonstrating that faster achievement of therapeutic tacrolimus concentrations is associated with better outcomes in terms of graft rejection and graft loss. Patients are at the highest risk of acute allograft rejection during the first 6 months post-transplant, necessitating more intense immunosuppression early on after transplant. This intense immunosuppression puts patients at risk for opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), cytomegalovirus (CMV), urinary tract infections (UTI), BK virus, etc. Tacrolimus is the first-line calcineurin inhibitor due to superior efficacy compared to cyclosporine. Major adverse events include nephrotoxicity, and neurotoxicity (seizures, tremors, paresthesias, headache, PRES, AMS). The purpose of this study was to evaluate incidence of biopsy proven acute rejection (BPAR) and/or graft failure in patients who achieved therapeutic tacrolimus concentrations <10 days after medication initiation compared to patients who achieved therapeutic tacrolimus concentrations >10 days after medication initiation.

Methods: This study was a single center, retrospective chart review of adult patients admitted to Ascension Saint Thomas Hospital West (ASTHW) for heart and/or kidney transplant who received tacrolimus as part of maintenance immunosuppression between August 1, 2022 and September 1, 2023. Patients who were pregnant or incarcerated were excluded. Patients were divided into two groups based on the time-to-therapeutic range tacrolimus concentrations following treatment initiation: < 10 days or > 10 days. The primary outcome was incidence of  BPAR and/or graft failure <6 months following heart and/or kidney transplantation. Secondary outcomes included incidence of infection, neurotoxicity, nephrotoxicity, and hospital readmission at 6 months post-transplant.

Results: A total of 99 patients were included in our analysis, of whom 48 were stratified into the achieved therapeutic tacrolimus concentrations  <10 days after medication initiation group and 51 into the achieved therapeutic tacrolimus concentrations >10 days after medication initiation group. The primary outcome of BPAR and/or graft failure occurred in 10 (10%) patients, with 4 patients in the <10 days group and 6 patients in the >10 days group (P= 0.74). There were no statistically significant differences between the groups in occurrence of CMV (8% vs. 8%, P> 0.99), UTI (8% vs. 16%, P= 0.359), BK virus (4% vs. 2%, P= 0.61), other treated bacterial, viral, or fungal infections (33% vs. 25%, P= 0.392), tremor (29% vs. 24%, P= 0.524), acute kidney injury (54% vs. 65%, P= 0.286), or readmission at 6 months (33% vs. 33%, P> 0.99).

Conclusion: In this study of kidney and/or heart transplant recipients receiving tacrolimus as maintenance immunosuppression, there were no statistically significant differences in rates of BPAR and/or graft failure, infection, neurotoxicity, nephrotoxicity, or readmission. Future studies evaluating time-to-therapeutic range should consider the varying time-in-therapeutic ranges.