Characterizing metabolic dysregulation in early-stage chronic kidney disease for diagnostic insights

Abstract

The progressive illness known as chronic kidney disease (CKD) can often be challenging to diagnose in its early stages with conventional diagnostic approaches such as serum creatinine and albumin assessment. Early-stage CKD (stages G1–G3) is defined by a GFR of ≥30 mL min⁻¹/1.73 m², which indicates normal to moderately reduced kidney function with or without symptoms of impaired kidney function. Identifying possible biomarkers for early detection and personalised treatment, as well as physiological changes linked to early CKD—an area that has not been fully investigated before—is the goal of the study to address this gap. We performed a metabolomic analysis using ¹H NMR on 115 human serum samples (24 healthy controls and 91 patients with early-stage CKD). MetaboAnalyst 6.0 was used for data pre-processing and statistical analyses (PCA, PLS-DA, OPLS-DA, ANOVA, and Wilcoxon Mann–Whitney test). Strong differentiation between CKD stages was achieved by random forest modelling. The KEGG database was used to perform pathway enrichment, and ROC analysis was used to evaluate the diagnostic value of important metabolites. Across CKD stages, significant changes were observed in ten different metabolites: myo-Inositol, glycerol, pyruvate, carnitine, phenylalanine, tyrosine, histidine, TMAO, 2-hydroxyisobutyrate, and 3-hydroxyisobutyrate (p < 0.05, VIP > 1). AUC values > 0.7 from ROC curves demonstrated its potential for diagnosis. Pathway analysis revealed significant dysregulation in the metabolism of inositol phosphate, tyrosine, histidine, and pyruvate, and biosynthesis of phenylalanine, tryptophan and tyrosine. This comprehensive metabolomics investigation identified potential early-stage CKD biomarkers in addition to significant metabolic abnormalities. These findings could help provide individualized care for early CKD management.