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

Abstract

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. 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. 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. 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.