Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury.
Metabolomic profiling demonstrates evidence for kidney and urine metabolic dysregulation in a piglet model of cardiac surgery-induced acute kidney injury.
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代谢组学研究证实了心脏手术所致急性肾损伤仔猪模型肾脏和尿液代谢紊乱的证据。
DOI：
10.1152/ajprenal.00039.2022
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发表时间：
2022-07-01
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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急性肾损伤（阿基）是先天性心脏病手术后发病的常见原因。然而，在诊断和治疗方面的进展仍然有限，部分原因是对机制的理解不足和缺乏相关的翻译模型。代谢组学方法可以帮助确定新的损伤机制和潜在的治疗靶点。在本研究中，我们使用了一个小猪模型的心肺转流与深低温停循环（CPB/DHCA）和有针对性的代谢分析的肾组织，尿液和血清，以评估特定的组织学急性肾损伤的动物的代谢变化。将有急性肾损伤的CPB/DHCA动物与无急性肾损伤和机械通气对照的CPB/DHCA动物进行比较。20只CPB/DHCA动物中有10只在CPB/DHCA后4 h发生急性肾损伤，而7只对照动物中没有发生急性肾损伤。与未损伤的肾脏相比，损伤的肾脏显示出不同的组织代谢特征（R2 = 0.93，Q2 = 0.53），有色氨酸和嘌呤代谢失调的证据。在急性肾损伤动物中，9种尿液代谢物显著不同，其模式提示有氧糖酵解增加。肾组织和尿液中的失调代谢物不重叠。CPB/DHCA强烈影响血清代谢谱，只有一种代谢物与急性肾损伤显著不同（焦谷氨酸，氧化应激的标志物）。总之，基于这些发现，肾脏色氨酸和嘌呤代谢是进一步机制和治疗研究的候选者。尿液有氧糖酵解生物标志物可以帮助诊断CPB/DHCA后的早期急性肾损伤，值得进一步评估。根据急性肾损伤，在该早期时间点测量的血清代谢物没有明显差异。新&值得注意的是，该项目在一个具有预防意义的大型心肺转流动物模型中，探索了小儿心脏手术后急性肾损伤（阿基）的代谢基础。在这里，我们提出了新的证据，在肾组织中失调的色氨酸catalysts和嘌呤catalysts和增加尿糖酵解中间体的动物谁发展组织学阿基。这些通路代表了该高危人群中术后阿基的潜在诊断和治疗靶点。
Acute kidney injury (AKI) is a common cause of morbidity after congenital heart disease surgery. Progress on diagnosis and therapy remains limited, however, in part due to poor mechanistic understanding and a lack of relevant translational models. Metabolomic approaches could help identify novel mechanisms of injury and potential therapeutic targets. In the present study, we used a piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB/DHCA) and targeted metabolic profiling of kidney tissue, urine, and serum to evaluate metabolic changes specific to animals with histological acute kidney injury. CPB/DHCA animals with acute kidney injury were compared with those without acute kidney injury and mechanically ventilated controls. Acute kidney injury occurred in 10 of 20 CPB/DHCA animals 4 h after CPB/DHCA and 0 of 7 control animals. Injured kidneys showed a distinct tissue metabolic profile compared with uninjured kidneys (R2 = 0.93, Q2 = 0.53), with evidence of dysregulated tryptophan and purine metabolism. Nine urine metabolites differed significantly in animals with acute kidney injury with a pattern suggestive of increased aerobic glycolysis. Dysregulated metabolites in kidney tissue and urine did not overlap. CPB/DHCA strongly affected the serum metabolic profile, with only one metabolite that differed significantly with acute kidney injury (pyroglutamic acid, a marker of oxidative stress). In conclusion, based on these findings, kidney tryptophan and purine metabolism are candidates for further mechanistic and therapeutic investigation. Urine biomarkers of aerobic glycolysis could help diagnose early acute kidney injury after CPB/DHCA and warrant further evaluation. The serum metabolites measured at this early time point did not strongly differentiate based on acute kidney injury. NEW & NOTEWORTHY This project explored the metabolic underpinnings of postoperative acute kidney injury (AKI) following pediatric cardiac surgery in a translationally relevant large animal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Here, we present novel evidence for dysregulated tryptophan catabolism and purine catabolism in kidney tissue and increased urinary glycolysis intermediates in animals who developed histological AKI. These pathways represent potential diagnostic and therapeutic targets for postoperative AKI in this high-risk population.
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功能性和管状损伤生物标志物可提高心脏手术后急性肾脏损伤的诊断精度。
影响因子：
24
作者：
Basu, Rajit K.;Wong, Hector R.;Krawczeski, Catherine D.;Wheeler, Derek S.;Manning, Peter B.;Chawla, Lakhmir S.;Devarajan, Prasad;Goldstein, Stuart L.
通讯作者：
Goldstein, Stuart L.
DOI：
10.1007/s00467-021-05095-8
发表时间：
2021-10
期刊：
Pediatric nephrology (Berlin, Germany)
影响因子：
--
作者：
Davidson JA;Frank BS;Urban TT;Twite M;Jaggers J;Khailova L;Klawitter J
通讯作者：
Klawitter J
影响因子：
8.8
作者：
Correia GD;Wooi Ng K;Wijeyesekera A;Gala-Peralta S;Williams R;MacCarthy-Morrogh S;Jiménez B;Inwald D;Macrae D;Frost G;Holmes E;Pathan N
通讯作者：
Pathan N
影响因子：
4.6
作者：
Huang H;van Dullemen LFA;Akhtar MZ;Faro ML;Yu Z;Valli A;Dona A;Thézénas ML;Charles PD;Fischer R;Kaisar M;Leuvenink HGD;Ploeg RJ;Kessler BM
通讯作者：
Kessler BM
DOI：
10.1016/j.jtcvs.2011.06.021
发表时间：
2012-02-01
影响因子：
6
作者：
Blinder, Joshua J.;Goldstein, Stuart L.;Jefferies, John L.
通讯作者：
Jefferies, John L.