AUTHOR=Füessl Louise , Kreuzer Lena , Nierychlewski Kajetan , Seibt Tobias , Stangl Manfred Johannes , Koliogiannis Dionysios , Meiser Bruno , Schwarz Markus , Fischereder Michael , Kemmner Stephan TITLE=The use of extended-release tacrolimus twice a day might be beneficial for selected kidney transplant recipients: a case report JOURNAL=Frontiers in Medicine VOLUME=11 YEAR=2024 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1336035 DOI=10.3389/fmed.2024.1336035 ISSN=2296-858X ABSTRACT=

The calcineurin inhibitor tacrolimus, which is available as an immediate- or extended-release formulation, is the standard-of-care immunosuppression after kidney transplantation with low rejection rates, especially in the first year after transplantation. However, its highly variable metabolism rate, narrow therapeutic window, and nephrotoxic side effects require close drug monitoring and individual dosing. Here, we describe first the application of extended-release tacrolimus (ER-Tac) twice daily with beneficial effects in a kidney transplant recipient under extensive therapeutic drug monitoring. A 47-year-old female kidney transplant recipient, who was identified as a fast metabolizer for tacrolimus, presented with declining allograft function and low tacrolimus through levels over time and 8 years after a second kidney transplantation despite the administration of high doses of ER-Tac once daily. Therefore, the area under the concentration–time curve (AUC) showed exceedingly high blood levels of ER-Tac. The latest biopsy of the kidney transplant showed arteriolar hyalinosis with pole vessel stenosis as a sign of chronic transplant vasculopathy and transplant glomerulopathy as a sign of chronic humoral rejection. After the exclusion of other options for immunosuppressive therapy due to the patient’s high immunological risk, the patient was switched from ER-Tac once daily to ER-Tac twice daily. After switching to ER-Tac twice daily, the AUC for oral tacrolimus decreased and the transplant function improved despite higher tacrolimus trough levels and a lower total dose administered. This case highlights the importance of careful therapeutic drug monitoring with the performance of an AUC in the follow-up management of kidney transplant recipients.