ORIGINAL RESEARCH article
Front. Transplant.
Sec. Thoracic Transplantation
The critical relationship between tacrolimus levels, acute kidney injury, and early chronic lung allograft dysfunction
Provisionally accepted
Roman Hauber1Luca Kohlhepp2Ignaz Briegel3
Tobias Veit3Juergen Barton3Bruno Meiser4,5
Christian Peter Schneider6Teresa Kauke3Rudolf Hatz3
Dominik Hoechter7
Nikolaus Kneidinger3
Jürgen Behr3*- 1Department of Internal Medicien II, Neuwittelsbach, Munich, Gwermany, Munich, Germany
- 2Artifical Intelligence and knwoledge systems, University of Würzburg, Wuerzburg, Germany
- 3Ludwig Maximilian University of Munich, Munich, Germany
- 4LMU Klinikum, Munich, Germany
- 5Transplant Center, LMU University Hospital, Munich, Germany
- 6Division of Thoracic Surgery, LMU University Hospital, Munich, Germany
- 7Department of Anesthesiology, LMU University Hospital, Munich, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Based on clinical observation we hypothesized that tacrolimus (TAC) exposure and acute kidney injury (AKI) are linked to the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). Methods: 509 out of 827 lung transplant recipients between 2000 and 2018 with full data set from the university hospital of Munich (LMU) were included in this study. In the context of a 10% reduction in FEV1 (CLAD10), tacrolimus and renal function are examined descriptively, inferentially, and by means of confounder analysis with regard to the occurrence of CLAD10. Results: 67 out of 509 LTx patients (13%) died during the first two years post LTx. In 38 of these 67 patients (57%) who showed CLAD10 within two years after LTx, we observed a temporal pattern of a peak in TAC levels followed by AKI and subsequently subtherapeutic TAC concentrations prior to the onset of CLAD10 within a few weeks. The confounder analysis shows a significant influence of renal failure and tacrolimus derailments on the hazard ratio for CLAD10. Conclusion: Our data suggest that a transient drop in TAC serum concentrations, often caused by a TAC induced AKI, may trigger the onset of CLAD10, and a subsequent elevated risk of premature death.
Keywords: Lung Transplantation, chronic lung allograft dysfunction, Clad, Tacrolimus, kidney injury
Received: 16 Sep 2025; Accepted: 29 Nov 2025.
Copyright: © 2025 Hauber, Kohlhepp, Briegel, Veit, Barton, Meiser, Schneider, Kauke, Hatz, Hoechter, Kneidinger and Behr. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jürgen Behr
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.