Influence of tacrolimus concentration-to-dose ratio on CLAD risk in lung transplant recipients

Lung transplantation remains a vital treatment for patients with end-stage respiratory diseases, yet chronic lung allograft dysfunction (CLAD) continues to be a major complication. Identifying predictive biomarkers to optimize post-transplant management is essential. The tacrolimus concentration-to-dose ratio (CDR) serves as an indicator of a patient's metabolizer status and has been linked to transplant outcomes in kidney recipients. This study investigates the relationship between tacrolimus CDR and CLAD occurrence.

We conducted a single-center retrospective study including adult lung transplant recipients treated with tacrolimus-based immunosuppression. Patients were stratified as rapid or slow metabolizers based on tacrolimus CDR at month 9 (M9). The primary endpoint was CLAD occurrence. Secondary objectives included assessing the impact of CDR variation over time on CLAD risk and identifying factors influencing CDR variability.

Among 84 patients, 32 (38%) developed CLAD. No significant difference in CLAD incidence was found between rapid and slow metabolizers at M9 (p = 0.267). However, increased CDR variability was significantly associated with a higher risk of CLAD (p < 0.001). Factors contributing to CDR variability included variability in tacrolimus trough concentrations, hospitalization for infections, and prolonged azole antifungal therapy.

Contrary to our hypothesis, tacrolimus metabolizer status at M9 was not predictive of CLAD. However, high intrapatient CDR variability was significantly associated with CLAD occurrence. Given the impact of infections and azole antifungal therapy on tacrolimus metabolism, these factors should be considered in post-transplant immunosuppressive management. Further studies are needed to confirm these findings and refine tacrolimus dosing strategies in lung transplant recipients.