Stage-dependent effects of systemic ASBT inhibition in a cholestasis-induced cholemic nephropathy mouse model
This study demonstrates that systemic inhibition of the apical sodium-dependent bile acid transporter (ASBTi) alleviates cholemic nephropathy across disease stages in a bile duct ligation mouse model. The greatest benefit was achieved when treatment was initiated early, coinciding with proximal tubular epithelial cell death, but even advanced features such as glomerular cysts were partially reversed. These findings highlight ASBTi as a promising therapeutic strategy for cholemic nephropathy, addressing a major unmet need in cholestatic liver disease. By targeting bile acid accumulation and related injury pathways, ASBTi may improve renal outcomes and broaden treatment options in affected patients.
Authors
- Tom Luedde (ORCID: https://orcid.org/0000-0002-6288-8821)
- Reham Hassan (ORCID: https://orcid.org/0000-0002-6569-7676)
- Mattias Mandorfer (ORCID: https://orcid.org/0000-0003-2330-0017)
- Peter Åkerblad (ORCID: https://orcid.org/0000-0001-5823-4369)
- Stefan Hoehme (ORCID: https://orcid.org/0000-0002-9716-9587)
- Adrian Friebel (ORCID: https://orcid.org/0000-0002-9157-4418)
- Guido Stirnimann (ORCID: https://orcid.org/0000-0003-3447-264X)
- Saul J. Karpen (ORCID: https://orcid.org/0000-0002-3379-7592)
- Daniela González (ORCID: https://orcid.org/0000-0002-0092-1411)
- Zhipeng Deng (ORCID: https://orcid.org/0000-0002-8582-2040)
- Brigitte Begher‐Tibbe (ORCID: https://orcid.org/0000-0003-2390-9148)
- Noha Abdelmageed (ORCID: https://orcid.org/0000-0002-0563-3144)
- Benedikt Simbrunner (ORCID: https://orcid.org/0000-0001-8181-9146)
- Lucia Ameis (ORCID: https://orcid.org/0009-0002-9420-6984)
- Ute Hofmann (ORCID: https://orcid.org/0000-0003-0823-9027)
- Ahmed Ghallab (ORCID: https://orcid.org/0000-0003-0695-3403)
- Jan Georg Hengstler (ORCID: https://orcid.org/0000-0002-1427-5246)
- Hannah Schmidt
- Kathrin Möllenhoff (ORCID: https://orcid.org/0000-0001-7861-3892)
- Julia Duda (ORCID: https://orcid.org/0000-0002-3894-0124)
- Matthias Schwab (ORCID: https://orcid.org/0000-0002-9984-075X)
- Maiju Myllys (ORCID: https://orcid.org/0000-0001-9117-4572)
- Hartmut Schmidt
- Ellen Strängberg
- Benedikt Hild (ORCID: https://orcid.org/0000-0002-9900-3484)
- Karolina Edlund (ORCID: https://orcid.org/0000-0002-0276-2143)
- Jörg Reinders (ORCID: https://orcid.org/0000-0003-1025-7849)
- Jörg Rahnenführer (ORCID: https://orcid.org/0000-0002-8947-440X)
- Tahany Abbas
- Mihael Vucur (ORCID: https://orcid.org/0000-0003-4078-1668)
- Michael A Trauner (ORCID: https://orcid.org/0000-0002-1275-6425)
- Zaynab Hobloss
- Katharina Derksen
- Rama Hendawi
- Erik Lindström (ORCID: https://orcid.org/0009-0009-4059-6287)
- Paul A. Dawson (ORCID: https://orcid.org/0000-0001-9760-4422)
- Abdellatief Seddek
- Qasim Siddiqui (ORCID: https://orcid.org/0009-0008-1243-2368)
Institutions
- University of Bern (CH)
- Emory University (US)
- University of Cologne (DE)
- Ipsen (France) (FR)
- Virginia Commonwealth University (US)
- South Valley University (EG)
- TU Dortmund University (DE)
- University Hospital of Bern (CH)
- Düsseldorf University Hospital (DE)
- Essen University Hospital (DE)
- Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology (DE)
- Saxon Institute for Applied Biotechnology (DE)
- Leibniz Research Centre for Working Environment and Human Factors (DE)
- Heinrich Heine University Düsseldorf (DE)
- Medical University of Vienna (AT)
- University of Tübingen (DE)
- Sohag University (EG)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101599
- Primary Topic
- Liver Disease and Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 0.00