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Analysis of human urine reveals metabolic changes related to the development of acute kidney injury following cardiac surgery

ABSTRACT: In an effort to identify novel biomarkers capable of predicting the development of acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB) use, urine specimens were collected before and at 4 and 24 hours after surgery from 106 patients and analyzed by means of nuclear magnetic resonance (NMR) spectroscopy and machine learning methods.

INSTRUMENT(S): Bruker

PROVIDER: MTBLS24 | MetaboLights | 2012-10-21

REPOSITORIES: MetaboLights

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Project description:Objectives: Secretion of extracellular vesicles (EV) and associated micro-RNAs (miR) is altered during cellular stress and may serve as biomarkers of organ injury. We hypothesized that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. Design: Predictive accuracy biomarker study performed in the cohort of the REVAKI-2 trial Setting: Single center ICU between September 2015 and September 2018 Interventions: Intravenous sildenafil citrate 12.5 mg kg-1 over 150 min or dextrose 5% at the commencement of surgery. Measurements and main results: Urine samples were collected before and 24 hours after the procedure from 93 cardiac surgery patients. Urine EV concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced to detect differentially expressed miR. Verification was performed with advanced TaqMan assays in samples from all patients. Urine EV concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for aquaporin-2 and β1-integrin also increasing. Pre surgery podocalyxin-positive EV were significantly lower, and β1-integrin EV werehigher in patients with AKI. The levels of the former correlated with the severity of theinjury. miR-125a-5p was expressed at higher levels in urine from patients with AKI stage 2/3. Levels of miR-10a-5p decreased after surgery in AKI patients; its levels correlated with the severity of the injury. Preoperative levels of podocalyxin EVs and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 80.9%) AKI prediction. Conclusions: Lower levels of podocalyxin-positive EV at baseline predict the severity of post-surgery AKI. Urine EV concentrations and miR expression offer excellent predictive accuracy when combined with commonly measured biomarkers.

			Action	DRS
	AKI_8_24_01_110722.zip	Other
	AKI_8_24_02_110722.zip	Other
	AKI_8_24_03_110722.zip	Other
	AKI_8_24_04_110722.zip	Other
	AKI_8_24_05_110722.zip	Other

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Analysis of human urine reveals metabolic changes related to the development of acute kidney injury following cardiac surgery

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