Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Tatscher, E.
Kidney injury in cholestasis and
advanced stage liver disease
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 105
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Fickert Peter
- Langner Cord
- Rosenkranz Alexander
- Altmetrics:
- Abstract:
- Kidney function is a major prognostic factor in patients with liver disease. Acute kidney injury (AKI) commonly occurs in patients with cirrhosis and may be related to prerenal causes such as fluid loss, intrinsic causes, or, although rare, postrenal causes. The commonly known hepatorenal syndrome-type AKI (HRS-AKI) represents a functional and potentially reversible form of progressive renal failure in the absence of identifiable causes. However, there is increasing evidence for structural renal changes at least in a subgroup of patients with liver diseases. Besides bacterial infections, fluid loss, and use of nephrotoxic drugs AKI in liver disease may be triggered by tubular toxicity of cholephiles. The latter became known as cholemic nephropathy, an increasingly recognized condition in patients with cholestasis describing impairment of renal function together with typical histological changes. These findings question the traditional concepts of predominant functional renal failure in liver disease, especially in the specific group of patients with cholestasis. The underlying pathophysiologic mechanisms of cholemic nephropathy are not entirely understood and clear diagnostic criteria and treatment options are still missing. The aim of this thesis was to explore the pathophysiologic mechanisms and possible therapeutic strategies of cholemic nephropathy. By modelling cholemic nephropathy in long-term common bile duct ligation (CBDL) in mice, a well-established mouse model for obstructive cholestasis with accumulation and alternative renal excretion of potentially nephrotoxic cholephiles such as bile acids, it was shown, that renal excreted bile acids might represent the culprits in pathogenesis of cholemic nephropathy. The fact that CBDL mice with a more hydrophilic and therefore less toxic bile acid pool (e.g. by genetic or dietary modulation of the bile acid composition) were protected, strongly argue for urinary excreted bile acids as causative factor for the characteristic morphological changes that can be found in cholemic nephropathy. These results may pave the way for novel strategies of prevention and treatment in the difficult to manage group of patients with advanced (cholestatic) liver diseases and concomitant impairment of renal function.