Metabolic Pathways Affected in Patients Undergoing Hemodialysis and Their Relationship with Inflammation

Abstract

Worldwide, 3.9 million individuals rely on kidney replacement therapy. They experience heightened susceptibility to cardiovascular diseases and mortality, alongside an increased risk of infections and malignancies, with inflammation being key to explaining this intensified risk. This study utilized semi-targeted metabolomics to explore novel metabolic pathways related to inflammation in this population. We collected pre- and post-session blood samples of patients who had already undergone one year of chronic hemodialysis and used liquid chromatography and high-resolution mass spectrometry to perform a metabolomic analysis. Afterwards, we employed both univariate (Mann–Whitney test) and multivariate (logistic regression with LASSO regularization) to identify metabolites associated with inflammation. In the univariate analysis, indole-3-acetaldehyde, 2-ketobutyric acid, and urocanic acid showed statistically significant decreases in median concentrations in the presence of inflammation. In the multivariate analysis, metabolites positively associated with inflammation included allantoin, taurodeoxycholic acid, norepinephrine, pyroglutamic acid, and L-hydroorotic acid. Conversely, metabolites showing negative associations with inflammation included benzoic acid, indole-3-acetaldehyde, methionine, citrulline, alphaketoglutarate, n-acetyl-ornithine, and 3-4-dihydroxibenzeneacetic acid. Non-inflamed patients exhibit preserved autophagy and reduced mitochondrial dysfunction. Understanding inflammation in this group hinges on the metabolism of arginine and the urea cycle. Additionally, the microbiota, particularly uricase-producing bacteria and those metabolizing tryptophan, play critical roles.