Untargeted metabolomics for plasma biomarker discovery for early chronic kidney disease diagnosis in pediatric...

Area of Science:

• Biochemistry
• Pediatric Nephrology
• Analytical Chemistry

Background:

• Pediatric chronic kidney disease (CKD) involves gradual, irreversible kidney damage.
• Early diagnosis is crucial for improving outcomes in pediatric CKD.
• Novel biomarkers are needed for timely detection of CKD in children.

Purpose of the Study:

• To identify novel biomarkers for the early diagnosis of pediatric CKD.
• To utilize untargeted metabolomics for biomarker discovery in pediatric plasma.
• To validate findings using two distinct chemometric approaches.

Main Methods:

• Untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) on pediatric plasma samples.
• Comparative analysis using Mass Profiler Professional (MPP) and Matlab R2015a software.
• Partial least squares discriminant analysis (PLS-DA) for biomarker model development.

Main Results:

• Five metabolites showed significant changes in pediatric CKD patients compared to controls.
• Increased levels of sphingosine-1-phosphate, n-butyrylcarnitine, cis-4-decenoylcarnitine, and an m/z 126.0930 feature were observed.
• Decreased levels of bilirubin were found, and a 5-metabolite model achieved 96-97% classification accuracy.

Conclusions:

• Identified metabolites, including sphingosine-1-phosphate and bilirubin, show potential as early diagnostic biomarkers for pediatric CKD.
• The developed PLS-DA model demonstrates high accuracy in classifying pediatric CKD patients.
• These findings support the use of metabolomics for early pediatric CKD detection in clinical settings.