Untargeted metabolomics for plasma biomarker discovery for early chronic kidney disease diagnosis in pediatric patients using LC-QTOF-MS

Abstract

Pediatric chronic kidney disease (CKD) is a clinical syndrome characterized by renal hypofunction occurring due to gradual and irreversible kidney damage that can further progress over time. New biomarkers may help early diagnosis of pediatric patients suffering from CKD and improve the outcome. Untargeted metabolomics based on LC-QTOF-MS has been used to find new biomarkers for the early diagnosis of CKD in plasma from pediatric patients. In order to avoid any bias in the determination of statistically significant entities as a consequence of the data analysis method followed, two different chemometric approaches have been used, Mass Profiler Professional (MPP) software and Matlab R2015a software. Metabolic fingerprints of control and CKD pediatric patients were compared and five metabolites which showed a significant change common to both data analysis procedures were identified. Sphingosine-1-phosphate, n-butyrylcarnitine, cis-4-decenoylcarnitine and an unidentified feature with 126.0930 m/z were found to be increased in plasma from pediatric patients with CKD, whereas bilirubin was significantly decreased. A partial least squares discriminant analysis model built with these 5 entities classified correctly 96% of the samples. In addition, when considering only early CKD patients against controls, a performance of 97% was obtained. Thus, these promising metabolites could be suitable biomarkers for the early diagnosis of pediatric CKD in a clinical setting.

Comprehensive Metabolic Signature of Renal Dysplasia in Children. A Multiplatform Metabolomics Concept

“…To the authors’ best knowledge, no publicly available studies have used metabolomics to investigate renal dysplasia, especially in children. Benito et al (2018) have evaluated the metabolic indicators of CKD in a cohort which included a pediatric population. The results of this study show increased levels of sphingosine-1-phosphate, n-butyrylcarnitine, and cis-4-decenoylcarnitine in plasma from patients with CKD and decreased level of bilirubin.…”

“…The results of this study show increased levels of sphingosine-1-phosphate, n-butyrylcarnitine, and cis-4-decenoylcarnitine in plasma from patients with CKD and decreased level of bilirubin. The authors have stressed that kidney function (estimated by the eGFR) is related to about one third of the detected metabolites in both the general and CKD populations ( Benito et al, 2018 ).…”

“…The kidney diseases that are most frequently studied by metabolomics include CKD, diabetic nephropathy, renal cell carcinoma, and acute kidney injury ( Kalim and Rhee, 2017 ). Kidney function, assessed by the estimated glomerular filtration rate (eGFR), has been related to about one third of the detected metabolites in both general and CKD populations ( Benito et al, 2018 ). Studies including the pediatric population are scarce since only one study performed on children was found.…”

New Insights from Metabolomics in Pediatric Renal Diseases

“…CKD is a major epidemiologic problem worldwide, in which renal hypofunction occurs due to irreversible kidney damage [ 70 ]. Due to its progressive course, CKD might represent a dramatic condition with severe long-term consequences [ 71 ], potentially leading to death [ 72 ]. In clinical practice, a common marker for renal function evaluation and CKD diagnosis, both in adults and children, is represented by the glomerular filtration rate (GFR), which in turn is estimated using the serum creatinine concentration [ 73 ].…”

Die Rolle des S1P-Rezeptors S1P5, des S1P-Transporters Spinster 2 und der kettenlängenspezifischen Ceramide bei Nierenfibrose

“…Es wurde herausgefunden, dass S1P5 sowohl in vitro als auch in vivo eine entscheidende Rolle für die Wanderung der natürlichen Killerzellen einnimmt (Walzer et al 2007;Mayol et al 2011;Drouillard et al 2018) gemessen (Bekpinar et al 2015). Bei Kindern, die unter chronischer Niereninsuffizienz litten, wurden hingegen höhere S1P-Spiele gemessen (Benito et al 2018).…”