Increased Tacrolimus Exposure in Kidney Transplant Recipients With COVID-19: Inflammation-Driven Downregulation of Metabolism as a Potential Mechanism

Kidney transplant recipients (KTRs) are at increased risk of severe COVID-19 disease compared to the general population. This is partly driven by their use of immunosuppressive therapy, which influences inflammatory responses and viral loads. Current guidelines suggest to withdraw mycophenolate while calcineurin inhibitors are often continued during a COVID-19 infection. However, clinical signs of calcineurin toxicity have been described in multiple COVID-19 positive KTRs. In this report we describe the course of tacrolimus exposure prior to, during, and post COVID-19 in observations from three clinical cases as well as four KTRs from a controlled trial population. We postulate inflammation driven downregulation of the CYP3A metabolism as a potential mechanism for higher tacrolimus exposure. To mitigate the risk of tacrolimus overexposure and toxicity therapeutic drug monitoring is recommended in KTRs with COVID-19 both in the in-, out-patient and home monitoring setting.

Automated summary

Kidney transplant recipients (KTRs) are more susceptible to severe COVID-19 due to the use of immunosuppressive therapy. Guidelines recommend discontinuing one medication during COVID-19 infection, but toxic effects of another medication have been observed. Therefore, therapeutic drug monitoring is recommended in KTRs with COVID-19.