Purpose: To describe the effect of tacrolimus (FK) time-in-therapeutic range (TTR) on incidence of cellular rejection (ACR) within the first year after lung transplantation (LT).

Methods: Single-center, retrospective cohort study of adult LT recipients (LTRs) on FK in year-one. Protocol trough targets were: 12-15 ng/mL for 6 months followed by 10-12 ng/mL for 6 months. FK percent TTR was calculated using Rosendaal linear interpolation method. Percent of levels-in-therapeutic range (LTR) was also calculated. Patients were grouped by TTR above and below 30%. Primary outcome was ACR burden (composite rejection standardization score (CRSS), range 0-6). Secondary outcome included high-grate ACR burden (CRSS > 2). Normality was assessed and univariate and multivariate parametric and nonparametric approaches were used where appropriate. Risk was assigned using univariate and multivariate logistic regression.

Results: 292 LTRs were included. Baseline demographics including bilateral lung (p=0.96), sex (p=.17), age (p=0.54), LAS (p=0.95), sensitized (p=0.55), induction agent (p=0.69), or azole antifungal use (p=0.1) were not different between groups. Mean year-one TTR and LTR were 22.1% (SD 10.1%) and 20% (SD 6.8%) respectively. Number of ACR events were not numerically different between groups (p=0.44). Each increase in TTR by 10% resulted in significantly lower burden of ACR events (OR 0.74, 95%CI 0.68-0.81, p<0.001); which remained significant when adjusting for lymphodepleting induction with alemtuzumab (LIA) and age (OR 0.81, 95%CI 0.66-0.995, p=0.045). Each increase in LTR by 10% resulted in significantly lower burden of ACR events (OR 0.72, 5%CI 0.65-0.79, p<0.001); which did not remain significant when adjusting for LIA and age (OR 0.81, 95%CI 0.62-1.07, p=0.14). TTR over 30% was associated with significantly less high-grade ACR (OR: 0.1, 95%CI 0.02-0.41, p=0.001); which remained significant when adjusting for LIA and age (OR: 0.1, 95%CI 0.22-0.46, p=0.003). LTR over 20% was associated with significantly less high-grade ACR (OR: 0.28, 5%CI 0.15-0.53, p<0.001); which remained significant when adjusting for LIA and age (OR: 0.15, 95%CI 0.06-0.4, p<0.001).

Conclusion: Increasing FK TTR is significantly associated with decreasing incidence and severity of ACR events within the first year after LT; even when adjusting for lymphodepletion and age.

CITATION INFORMATION: Ensor C, Harrigan K, Venkataramanan R, Morrell M, Moore C, Hayanga J, Crespo M, DCunha J, Zeevi A, McDyer J. Increasing Tacrolimus Time-in-Therapeutic Range Is Associated with Less Cellular Rejection in Lung Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress