Serum metabolomics identifies gut-derived uremic toxins and bile acid dysregulation associated with chronic kidney disease severity
Abstract
Chronic kidney disease (CKD) affects more than 700 million people worldwide, however conventional biomarkers like creatinine cannot identify early-stage disease or accurately predict progression. In this study, untargeted and targeted metabolomic approaches were combined to identify novel biomarkers relevant for CKD staging and early detection in an underrepresented Egyptian population. Untargeted ultra-high-performance liquid chromatography–mass spectrometry analyses in both ionization modes were performed on serum samples of 50 CKD patients [25 early-stage CKD (eCKD), 25 end-stage kidney disease (ESKD)] and 20 controls. Differential metabolites were determined by univariate and multivariate analyses, coupled with pathway analysis and correlations with estimated glomerular filtration rate (eGFR). Five discriminating metabolites (p-hydroxyphenyllactic acid, indoxyl sulfate, xanthurenic acid, trimethylamine-N-oxide, and glycochenodeoxycholate) were subjected to targeted LC-MS/MS validation in an independent cohort (35 eCKD, 35 ESKD, 15 controls). Gut-derived uremic toxins, bile acid and tryptophan–kynurenine metabolic dysregulation were associated with CKD severity. p-hydroxyphenyllactic acid, xanthurenic acid, glutamyl-valine and indoxyl sulfate showed strong inverse correlations with eGFR (r = -0.75 to -0.85). A five-metabolite panel (indoxyl sulfate, p-hydroxyphenyllactic acid, trimethylamine-N-oxide, glycochenodeoxycholate, xanthurenic acid), demonstrated superior…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 700 participants or records.
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