Tacrolimus time-in-therapeutic range is associated with freedom from acute rejection and graft failure following intestinal transplantation

Clin Transplant. 2021 Jun;35(6):e14291. doi: 10.1111/ctr.14291. Epub 2021 Apr 3.

Abstract

Background: Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical outcomes.

Methods: This was a single-center review of all adult non-liver containing intestinal allograft recipients from 2011 to 2018. Patients received lymphocyte depleting induction and maintenance immunosuppression consisting of tacrolimus and a corticosteroid taper. Tacrolimus time-in-therapeutic range (TAC-TTR) was calculated for all patients from the date of transplant until 1-year post-transplant using Rosendaal's method. Cox-Proportional hazards modeling was utilized to assess freedom from acute rejection and graft failure stratified by TAC-TTR quartile.

Results: 47 patients were included in the review. Mean TAC-TTR for the cohort was 30.2% ± 11.4. Fifteen episodes of acute rejection were observed, 8 of which were severe. Patients in the highest TAC-TTR quartile >36% had a lower incidence of acute rejection and graft failure relative to patients with a TAC-TTR <20%. Cox-Proportional hazards modeling found a 10% decrease in TAC-TTR was associated with an increased hazard for acute rejection (2.03), severe acute rejection (2.19), and graft loss (3.33).

Conclusion: The results of this study suggest that decreasing TAC-TTR is a risk factor for both acute rejection as well as intestinal allograft failure.

Keywords: drug monitoring; graft rejection; immunosuppression; intestinal transplantation; tacrolimus.

MeSH terms

  • Adult
  • Freedom
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Tacrolimus* / therapeutic use

Substances

  • Immunosuppressive Agents
  • Tacrolimus