Kidney international · 2026
Peritoneal dialysis induces hepatic metabolic stress as an instigator for systemic inflammation.
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Eibensteiner Fabian, Herzog Rebecca, Trauner Michael, Philippe Cécile, Patronas Eva-Maria, Sacnun Juan Manuel, Sobieszek Isabel Joanna, Unterwurzacher Markus, Wagner Anja, Lang Elisabeth, Fuchs Claudia Daniela, Daniel-Fischer Lisa, Boehm Michael, Haschemi Arvand, Dixon Emmanuel Dauda, Scharnagl Hubert, Stojakovic Tatjana, Koenig Franz, Alper Seth Leo, Vychytil Andreas, Kratochwill Klaus, Aufricht Christoph
Аннотация
INTRODUCTION: Peritoneal dialysis (PD) is a lifesaving therapy in patients with kidney failure, but results in daily intraperitoneal glucose administration corresponding to 50% of the recommended energy intake, most of which enters the portal circulation. As the impact of this glucose exposure on liver and metabolic health remains unclear, we explored hepatic and systemic metabolic effects of PD.
METHODS: Healthy mice and mice with chronic kidney disease (5/6 nephrectomy C57BL/6 aged 12-14 weeks) underwent seven weeks of PD. Combining morphologic studies, untargeted tissue proteomics, targeted plasma metabolomics and spatial transcriptomics, we assessed hepatic molecular and metabolic effects of PD. Gut- and gut-vascular barriers, systemic and hepatic lipopolysaccharide abundance and zonal transcriptional changes were assessed with multiplexed spatial single-cell analysis and transcriptomics.
RESULTS: Intraperitoneally administered glucose during PD was rapidly taken up by the liver and induced hepatic metabolic inflammation. Portal-venous glucose overload bypassing the gastrointestinal tract resulted in increased glucose-to-cholesterol shunting with elevated plasma cholesterol levels, despite the absence of hepatic steatosis or glycogen storage. Increased oxidative stress and endotoxin load were associated with reduced hepatic Kupffer cell numbers without increased gut permeability.
CONCLUSIONS: Ours study found chronic hepatic metabolic stress induced by PD. Evidence of hepatic glucotoxicity and oxidative stress as instigators for systemic metabolic inflammation induced by PD suggests that similar pathologic mechanisms could also contribute to increased cardiometabolic risk on chronic PD.
METHODS: Healthy mice and mice with chronic kidney disease (5/6 nephrectomy C57BL/6 aged 12-14 weeks) underwent seven weeks of PD. Combining morphologic studies, untargeted tissue proteomics, targeted plasma metabolomics and spatial transcriptomics, we assessed hepatic molecular and metabolic effects of PD. Gut- and gut-vascular barriers, systemic and hepatic lipopolysaccharide abundance and zonal transcriptional changes were assessed with multiplexed spatial single-cell analysis and transcriptomics.
RESULTS: Intraperitoneally administered glucose during PD was rapidly taken up by the liver and induced hepatic metabolic inflammation. Portal-venous glucose overload bypassing the gastrointestinal tract resulted in increased glucose-to-cholesterol shunting with elevated plasma cholesterol levels, despite the absence of hepatic steatosis or glycogen storage. Increased oxidative stress and endotoxin load were associated with reduced hepatic Kupffer cell numbers without increased gut permeability.
CONCLUSIONS: Ours study found chronic hepatic metabolic stress induced by PD. Evidence of hepatic glucotoxicity and oxidative stress as instigators for systemic metabolic inflammation induced by PD suggests that similar pathologic mechanisms could also contribute to increased cardiometabolic risk on chronic PD.