Abstract

Acute kidney injury (AKI) is defined as a rapid decline in kidney function. The associated syndromes may lead to increased morbidity and mortality, but its early detection remains difficult. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we analyzed the urinary metabolomic profile of patients admitted to the intensive care unit (ICU) after invasive surgery. Urine samples were collected at six time points: before surgery, at ICU admission and 6, 12, 24 and 48 h after. First, urine samples from 61 initial patients (non-AKI: 23, mild AKI: 24, severe AKI: 14) were measured, followed by the measurement of urine samples from 60 additional patients (non-AKI: 40, mild AKI: 20). Glycine and ethanolamine were decreased in patients with AKI compared with non-AKI patients at 6–24 h in the two groups. The linear statistical model constructed at each time point by machine learning achieved the best performance at 24 h (median AUC, area under the curve: 89%, cross-validated) for the 1st group. When cross-validated between the two groups, the AUC showed the best value of 70% at 12 h. These results identified metabolites and time points that show patterns specific to subjects who develop AKI, paving the way for the development of better biomarkers.

Highlights

  • Acute kidney injury (AKI) is defined as a severe decline in kidney function within a few hours

  • Urine samples were collected at six time points from patients who underwent surgery

  • Urine samples were collected from patients in Nagoya University Hospital who were admitted to the intensive care unit (ICU) after invasive surgery

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Summary

Introduction

Acute kidney injury (AKI) is defined as a severe decline in kidney function within a few hours It is caused by various factors, including decreased blood flow during a major surgery or pain medication overuse. Because it is associated with morbidity and mortality, understanding the mechanisms underlying AKI progression and identifying body fluid biomarkers are urgently needed to develop medications for patients with AKI. To this end, several studies have investigated the molecular profiles of blood and urine during the progression of AKI. The levels of NGAL [2], cystatin

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