Elevated tacrolimus levels among COVID-19 kidney transplant recipients are associated with worse disease severity and clinical outcomes.

Background: The therapeutic effects of immunosuppressive drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections causing coronavirus disease 2019 (COVID-19) are being actively investigated. However, COVID-19's potential effects on serum calcineurin inhibitor levels have only been described recently. This study aimed to evaluate COVID-19's effect on tacrolimus levels in renal transplant recipients with moderate to severe symptoms and to assess their potential correlation with disease severity.

Materials And Methods: We retrospectively investigated 50 kidney transplant recipients with moderate to severe COVID-19. Their tacrolimus trough level on admission was compared to baseline levels, and their laboratory measurements and clinical course were reviewed on days 1 (admission), 7, 14, and 28.

Results: We found that 90% of patients had admission tacrolimus trough levels above baseline, with a mean increase of 176%. In addition, 71% had tacrolimus trough levels ≥ 50% above baseline, and 40% had supra-therapeutic trough levels of > 15 ng/mL. Supra-therapeutic trough levels were associated with greater hypoxemic respiratory failure, acute kidney injury, and increased 30-day mortality.

Conclusion: Elevated tacrolimus levels occur in many renal transplant recipients with moderate to severe COVID-19 and are associated with worse clinical outcomes. Close drug monitoring is crucial to avoid toxicities and minimize over-immunosuppression complications.