Choline Supplementation Attenuates Experimental Sepsis-Associated Acute Kidney Injury.
Choline Supplementation Attenuates Experimental Sepsis-Associated Acute Kidney Injury.
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DOI：
10.1152/ajprenal.00033.2022
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发表时间：
2022-07
期刊：
影响因子：
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通讯作者：
Denise C. Hasson;Miki Watanabe-Chailland;L. Romick-Rosendale;Adeleine Koterba;Dashiell S Miner;P. Lahni;Q. Ma;S. Goldstein;P. Devarajan;Stephen W. Standage
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文献类型：
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作者：
Denise C. Hasson;Miki Watanabe-Chailland;L. Romick-Rosendale;Adeleine Koterba;Dashiell S Miner;P. Lahni;Q. Ma;S. Goldstein;P. Devarajan;Stephen W. Standage
急性肾损伤(AKI)在危重病患者中很常见，脓毒症是其主要原因。与其他AKI病因相比，脓毒症相关性AKI(SA-AKI)导致更高的发病率和死亡率，但其潜在的机制尚不完全清楚。代谢组学技术可以表征细胞能量的紊乱，但很少有发现分析评估SA-AKI的代谢组学特征。为了确定适合治疗干预的代谢紊乱，我们评估了脓毒症小鼠和危重儿童的血浆和尿代谢物，并将它们与AKI状态进行了比较。在小鼠和人的SA-AKI中，与胆碱和中枢碳代谢相关的代谢物不同地丰富。SA-AKI小鼠肾脏和肝脏胆碱代谢相关酶基因表达发生改变。腹腔注射胆碱可改善脓毒症小鼠的肾功能。由于脓毒症儿童患者表现出与脓毒症小鼠相似的代谢特征，补充胆碱可能会减轻儿童脓毒症AKI。
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 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 were altered in the kidneys and liver of mice with SA-AKI. Treatment with intraperitoneal choline improved renal function in septic mice. Because septic pediatric patients displayed similar metabolomic profiles to septic mice, choline supplementation may attenuate pediatric septic AKI.