Time to Therapeutic Tacrolimus Serum Concentrations and the Impact on Early Acute Cellular Rejection in Adult Lung Transplant Recipients

Abstract

Purpose Acute cellular rejection (ACR) affects up to 55% of lung transplant recipients (LTR) within the first year post-transplant. Maintenance immunosuppression regimens include calcineurin inhibitors, antimetabolites, and corticosteroids. Previous studies have shown that early ACR can lead to more severe rejection episodes within the first year post-transplant. The aim of this study is to evaluate the relationship between the time to therapeutic tacrolimus trough concentrations immediately after lung transplant and early clinical ACR post lung transplant. Methods This was a single center, retrospective cohort study of 208 adult LTR transplanted between March 1, 2012 and December 31, 2015 at NewYork-Presbyterian Hospital, Columbia University Irving Medical Center. Recipients were stratified into four groups based on the time to therapeutic tacrolimus concentrations: 0-7, 8-14, 15-29, and ≥30 days post-transplant. Therapeutic tacrolimus trough concentrations were defined as two consecutive levels between 10-15 ng/mL. The primary outcome was the incidence of clinical ACR 6 weeks post-transplant. Clinical ACR included both biopsy proven rejection and treated rejection. Secondary outcomes included biopsy proven ACR 4 and 12 weeks post-transplant and the incidence of acute kidney injury 7, 14, and 30 days post-transplant. Multivariable logistic regression was performed to assess the primary outcome with adjustment for donor age, recipient age, recipient sex, primary graft dysfunction (PGD) within 72 hours post-transplant, and pre-transplant HLA sensitization. Results The incidence of clinical ACR within 6 weeks post-transplant did not differ between groups: 68%, 66%, 71%, and 71% in the 0-7, 8-14, 15-29, and ≥30 days post-transplant groups, respectively (p=0.94). No differences were seen in adjusted and unadjusted analysis. No difference was found in the incidence of AKI within 7 (p=0.25) or 30 (p=0.32) days post-transplant. The incidence of AKI within 14 days was higher in the 15-29 day group (26%), compared to 7%, 14%, 7% in groups 0-7, 8-14, and ≥30 days, respectively (p=0.05). Conclusion There was no difference in the incidence of early clinical ACR among adult LTR who achieved therapeutic tacrolimus trough concentrations 0-7, 8-14, 15-29, or ≥30 days post-transplant.