Choline supplementation attenuates experimental sepsis-associated acute kidney injury
Acute kidney injury (AKI) is common in critically ill patients, and sepsis is its leading cause. Sepsis-associated AKI (SA-AKI) causes greater morbidity and mortality than other AKI etiologies, yet the underlying mechanisms are incompletely understood. Metabolomic technologies can characterize cellular energy derangements, but few discovery analyses have evaluated the metabolomic profile of SA-AKI. To identify metabolic derangements amenable to therapeutic intervention, we assessed plasma and urine metabolites in septic mice and critically ill children and compared them by AKI status. Metabolites related to choline and central carbon metabolism were differentially abundant in SA-AKI in both mice and humans. Gene expression of enzymes related to choline metabolism was altered in the kidneys and liver of mice with SA-AKI. Treatment with intraperitoneal choline improved renal function in septic mice. Because pediatric patients with sepsis displayed similar metabolomic profiles to septic mice, choline supplementation may attenuate pediatric septic AKI.NEW & NOTEWORTHY Altered choline metabolism plays a role in both human and murine sepsis-associated acute kidney injury (SA-AKI), and choline administration in experimental SA-AKI improved renal function. These findings indicate that 1) mouse models can help interrogate clinically relevant mechanisms and 2) choline supplementation may ameliorate human SA-AKI. Future research will investigate clinically the impact of choline supplementation on human renal function in sepsis and, using model systems, how choline mediates its effects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:323 |
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| Enthalten in: |
American journal of physiology. Renal physiology - 323(2022), 3 vom: 01. Sept., Seite F255-F271 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hasson, Denise C [VerfasserIn] |
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| Links: |
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| Themen: |
Acute kidney injury |
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| Anmerkungen: |
Date Completed 19.08.2022 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajprenal.00033.2022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM343545934 |
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| 520 | |a Acute kidney injury (AKI) is common in critically ill patients, and sepsis is its leading cause. Sepsis-associated AKI (SA-AKI) causes greater morbidity and mortality than other AKI etiologies, yet the underlying mechanisms are incompletely understood. Metabolomic technologies can characterize cellular energy derangements, but few discovery analyses have evaluated the metabolomic profile of SA-AKI. To identify metabolic derangements amenable to therapeutic intervention, we assessed plasma and urine metabolites in septic mice and critically ill children and compared them by AKI status. Metabolites related to choline and central carbon metabolism were differentially abundant in SA-AKI in both mice and humans. Gene expression of enzymes related to choline metabolism was altered in the kidneys and liver of mice with SA-AKI. Treatment with intraperitoneal choline improved renal function in septic mice. Because pediatric patients with sepsis displayed similar metabolomic profiles to septic mice, choline supplementation may attenuate pediatric septic AKI.NEW & NOTEWORTHY Altered choline metabolism plays a role in both human and murine sepsis-associated acute kidney injury (SA-AKI), and choline administration in experimental SA-AKI improved renal function. These findings indicate that 1) mouse models can help interrogate clinically relevant mechanisms and 2) choline supplementation may ameliorate human SA-AKI. Future research will investigate clinically the impact of choline supplementation on human renal function in sepsis and, using model systems, how choline mediates its effects | ||
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| 650 | 4 | |a central carbon metabolism | |
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| 700 | 1 | |a Miner, Dashiell S |e verfasserin |4 aut | |
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| 700 | 1 | |a Ma, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Goldstein, Stuart L |e verfasserin |4 aut | |
| 700 | 1 | |a Devarajan, Prasad |e verfasserin |4 aut | |
| 700 | 1 | |a Standage, Stephen W |e verfasserin |4 aut | |
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