Uremic Toxins and Inflammation: Metabolic Pathways Affected in Stage 5 Kidney Disease

• DOI: 10.20944/preprints202402.0580.v1
• Publication Date: 2024-02-12T08:09:11Z
• Authors: María Peris-Ferná...; Marta Roca-Marugán; Julià L Amengual; Angel Balaguer; Iris Viejo-Boyano; Amparo Soldevila-...; Ramón Devesa-Such; Pilar Sánchez-Pérez; Julio Hernández-J...
• Keywords: Uremic Toxins

Chronic kidney disease (CKD) affects approximately 12% of the global population posing a significant health threat. Inflammation plays crucial role in uremic phenotype CKD contributing to elevated cardiovascular and overall mortality affected individuals. This study aimed explore novel metabolic pathways non-dialysis dependent stage 5 patients using semitargeted metabolomics. In prospective observational design involving 50 patients, blood samples collected before initial hemodialysis session underwent liquid chromatography high resolution mass spectrometer analysis. Univariate (Mann-Whitney test) multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated inflammation. Notably, adenosine-5’-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, 2-ketobutyric acid exhibited differences presence Cholic acid, homogentisic 2-phenylpropionic displayed opposing patterns. Multivariate analysis indicated increased inflammation risk certain metabolites (N-Butyrylglycine, 2-Oxoisopentanoic pyruvate), while others (homogentisic 2-Phenylpropionic 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related defective mitochondrial fatty beta oxidation branched-chain amino breakdown CKD, shedding light on cellular energy production offering insights for further clinical validation.