Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

María Peris-Fernández
* ,
Marta Roca-Marugán
ORCID logo ,
Julià L Amengual
,
Angel Balaguer
,
Iris Viejo-Boyano
,
Amparo Soldevila-Orient
,
Ramón Devesa-Such
,
Pilar Sánchez-Pérez
ORCID logo ,
Julio Hernández-Jaras
ORCID logo
Version 1 : Received: 9 February 2024 / Approved: 9 February 2024 / Online: 9 February 2024 (14:06:16 CET)

A peer-reviewed article of this Preprint also exists.

Peris-Fernández, M.; Roca-Marugán, M.; Amengual, J.L.; Balaguer-Timor, Á.; Viejo-Boyano, I.; Soldevila-Orient, A.; Devesa-Such, R.; Sánchez-Pérez, P.; Hernández-Jaras, J. Uremic Toxins and Inflammation: Metabolic Pathways Affected in Non-Dialysis-Dependent Stage 5 Chronic Kidney Disease. Biomedicines 2024, 12, 607. Peris-Fernández, M.; Roca-Marugán, M.; Amengual, J.L.; Balaguer-Timor, Á.; Viejo-Boyano, I.; Soldevila-Orient, A.; Devesa-Such, R.; Sánchez-Pérez, P.; Hernández-Jaras, J. Uremic Toxins and Inflammation: Metabolic Pathways Affected in Non-Dialysis-Dependent Stage 5 Chronic Kidney Disease. Biomedicines 2024, 12, 607.

Abstract

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

Keywords

inflammation; ackd; metabolomics; energy metabolism; uremic toxins

Subject

Medicine and Pharmacology, Urology and Nephrology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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