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Increased Tacrolimus Exposure in Kidney Transplant Recipients With COVID-19: Inflammation-Driven Downregulation of Metabolism as a Potential Mechanism.
Klomp, Sylvia D; Meziyerh, Soufian; Vissers, Maurits F J M; Moes, Dirk J A R; Arends, Eline J; Teng, Y K Onno; Swen, Jesse J; de Vries, Aiko P J.
  • Klomp SD; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
  • Meziyerh S; Leiden Network for Personalised Therapeutics, Leiden University Medical Center, Leiden, Netherlands.
  • Vissers MFJM; Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
  • Moes DJAR; Leiden Transplant Center, Leiden University Medical Center, Leiden, Netherlands.
  • Arends EJ; Centre for Human Drug Research, Leiden, Netherlands.
  • Teng YKO; Leiden University Medical Center, Leiden, Netherlands.
  • Swen JJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
  • de Vries APJ; Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
Transpl Int ; 35: 10269, 2022.
Article in English | MEDLINE | ID: covidwho-1938660
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Kidney Transplantation / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: Transpl Int Journal subject: Transplantation Year: 2022 Document Type: Article Affiliation country: Ti.2022.10269

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Kidney Transplantation / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Humans Language: English Journal: Transpl Int Journal subject: Transplantation Year: 2022 Document Type: Article Affiliation country: Ti.2022.10269