Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fickert, P; Krones, E; Pollheimer, MJ; Thueringer, A; Moustafa, T; Silbert, D; Halilbasic, E; Yang, M; Jaeschke, H; Stokman, G; Wells, RG; Eller, K; Rosenkranz, AR; Eggertsen, G; Wagner, CA; Langner, C; Denk, H; Trauner, M.
Bile acids trigger cholemic nephropathy in common bile-duct-ligated mice.
Hepatology. 2013; 58(6):2056-2069
Doi: 10.1002/hep.26599
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Fickert Peter
- Tatscher Elisabeth
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Eller Kathrin
- Halilbasic Emina
- Langner Cord
- Moustafa Tarek
- Pollheimer Marion
- Rosenkranz Alexander
- Silbert-Wagner Dagmar
- Trauner Michael
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Tubular epithelial injury represents an underestimated but important cause of renal dysfunction in patients with cholestasis and advanced liver disease, but the underlying mechanisms are unclear. To address the hypothesis that accumulation and excessive alternative urinary elimination of potentially toxic bile acids (BAs) may contribute to kidney injury in cholestasis, we established a mouse model for detailed in vivo time course as well as treatment studies. Three-day common bile duct ligation (CBDL) induced renal tubular epithelial injury predominantly at the level of aquaporin 2-positive collecting ducts with tubular epithelial and basement membrane defects. This was followed by progressive interstitial nephritis and tubulointerstitial renal fibrosis in 3-, 6-, and 8-week CBDL mice. Farnesoid X receptor knockout mice (with a hydrophilic BA pool) were completely protected from CBDL-induced renal fibrosis. Prefeeding of hydrophilic norursodeoxycholic acid inhibited renal tubular epithelial injury in CBDL mice. In addition, we provide evidence for renal tubular injury in cholestatic patients with cholemic nephropathy. We characterized a novel in vivo model for cholemic nephropathy, which offers new perspectives to study the complex pathophysiology of this condition. Our findings suggest that urinary-excreted toxic BAs represent a pivotal trigger for renal tubular epithelial injury leading to cholemic nephropathy in CBDL mice. © 2013 by the American Association for the Study of Liver Diseases.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bile Acids and Salts - adverse effects
- Cholestasis - complications
- Common Bile Duct -
- Disease Models, Animal -
- Kidney Diseases - chemically induced
- Kidney Tubules - injuries
- Ligation -
- Male -
- Mice -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Nephritis, Interstitial - etiology
- Receptors, Cytoplasmic and Nuclear - genetics
- Ursodeoxycholic Acid - analogs & derivatives Ursodeoxycholic Acid - therapeutic use