Urinary Metabolome Analyses of Patients with Acute Kidney Injury Using Capillary Electrophoresis-Mass Spectrometry

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: 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.

CKD Urine Metabolomics: Modern Concepts and Approaches

“…Furthermore, resolution and sensitivity enhancement could be achieved by different MS instrumentation. The prevalent amount of CKD metabolomic works were made using time-of-flight mass spectrometry (TOF-MS) [ 23 , 36 , 39 , 42 ] and quadrupole time-of-flight mass spectrometry (Q-TOF-MS) [ 43 , 44 , 45 , 46 ], which is characterized by high sensitivity, fast scanning speeds, and accurate mass measurements. However, in one of the works, both Q-TOF-MS and reconstitution techniques were performed [ 40 ].…”

“…To overcome this, in tandem, MS or flow-injection MS methodic protein is precipitated by acetonitrile, methanol, or their water solutions being added in the sample, followed by centrifugation. To make the sample extra purified, the ultrafiltration stage is included in the sample preparation [ 42 , 47 ]. Some experiments consolidate the centrifugation and filtration stages using microspin filters [ 49 ].…”

“…In MS, molecules are identified and quantified by measuring the signal level of the mass-to-charge ratio of the ions ( m / z ) derived from those molecules. There are many techniques for producing ions in MS. Usually, in urine metabolomics, electrospray ionization (ESI) [ 42 , 43 , 47 ], chemical ionization (CI), and electron ionization (EI) [ 38 ] are present. One of the latest works in our scope used heated electrospray ionization (HESI) [ 48 ].…”

Recent developments in capillary and microchip electroseparations of peptides (2021–mid‐2023)

“…Detection and identification of particular peptides in complex biomatrices are of great importance also in peptidomic and proteomic analyses of biological fluids (blood, serum, plasma, cerebrospinal fluid, urine, and saliva) [231]. It can result in the discovery of new specific peptide biomarkers applicable in diagnosis, therapy, and prognosis of some diseases, for example, various kidney diseases [235][236][237], Alzheimer's disease [5], prostate cancer [238], cardiovascular diseases [236], COVID-19 [239], and lupus nephritis (LN) disease [6].…”

The association between albumin corrected anion gap and ICU mortality in acute kidney injury patients requiring continuous renal replacement therapy

“…Acute kidney injury (AKI), characterized by a rapid weakening of kidney function, is a complex clinical disorder that carries a high societal, economic, and personal burden worldwide [ 1 , 2 ]. Moreover, AKI is one of the most common reasons for an intensive care unit (ICU) admission and affects 33–66% of adult critically ill patients [ 3 ].…”