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体外循环婴幼儿心脏手术后并发术后急性肾损伤的血清代谢组学特征

Serum metabolic profile of postoperative acute kidney injury following infant cardiac surgery with cardiopulmonary bypass.

机构信息

Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, CO, USA.

Children's Hospital Colorado Research Institute, Aurora, CO, USA.

出版信息

Pediatr Nephrol. 2021 Oct;36(10):3259-3269. doi: 10.1007/s00467-021-05095-8. Epub 2021 May 5.

Abstract

BACKGROUND

We sought to determine differences in the circulating metabolic profile of infants with or without acute kidney injury (AKI) following cardiothoracic surgery with cardiopulmonary bypass (CPB).

METHODS

We performed a secondary analysis of preoperative and 24-h postoperative serum samples from infants ≤ 120 days old undergoing CPB. Metabolic profiling of the serum samples was performed by targeted analysis of 165 serum metabolites via tandem mass spectrometry. We then compared infants who did or did not develop AKI in the first 72 h postoperatively to determine global differences in the preoperative and 24-h metabolic profiles in addition to specific differences in individual metabolites.

RESULTS

A total of 57 infants were included in the study. Six infants (11%) developed KDIGO stage 2/3 AKI and 13 (23%) developed stage 1 AKI. The preoperative metabolic profile did not differentiate between infants with or without AKI. Infants with severe AKI could be moderately distinguished from infants without AKI by their 24-h metabolic profile, while infants with stage 1 AKI segregated into two groups, overlapping with either the no AKI or severe AKI groups. Differences in these 24-h metabolic profiles were driven by 21 metabolites significant at an adjusted false discovery rate of < 0.05. Prominently altered pathways include purine, methionine, and kynurenine/nicotinamide metabolism.

CONCLUSION

Moderate-to-severe AKI after infant cardiac surgery is associated with changes in the serum metabolome, including prominent changes to purine, methionine, and kynurenine/nicotinamide metabolism. A portion of infants with mild AKI demonstrated similar metabolic changes, suggesting a potential role for metabolic analysis in the evaluation of lower stage injury.

摘要

背景

我们旨在确定体外循环(CPB)下心肺手术后伴有或不伴有急性肾损伤(AKI)的婴儿循环代谢谱的差异。

方法

我们对接受 CPB 的≤120 天龄婴儿进行了术前和术后 24 小时血清样本的二次分析。通过串联质谱对 165 种血清代谢物进行靶向分析,对血清样本进行代谢谱分析。然后,我们比较了术后 72 小时内发生或未发生 AKI 的婴儿,以确定术前和 24 小时代谢谱的总体差异以及个别代谢物的具体差异。

结果

共有 57 名婴儿纳入研究。6 名婴儿(11%)发生 KDIGO 2/3 期 AKI,13 名婴儿(23%)发生 1 期 AKI。术前代谢谱不能区分有无 AKI 的婴儿。严重 AKI 婴儿的 24 小时代谢谱可以与无 AKI 婴儿中度区分,而 1 期 AKI 婴儿则分为两组,与无 AKI 或严重 AKI 组重叠。这些 24 小时代谢谱的差异是由 21 种代谢物引起的,这些代谢物在调整后的假发现率<0.05 时有显著差异。显著改变的途径包括嘌呤、蛋氨酸和犬尿氨酸/烟酰胺代谢。

结论

婴儿心脏手术后中重度 AKI 与血清代谢组学变化相关,包括嘌呤、蛋氨酸和犬尿氨酸/烟酰胺代谢的显著变化。一部分轻度 AKI 婴儿表现出相似的代谢变化,提示代谢分析在评估较低阶段损伤中具有潜在作用。

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