Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Prognostic Significance of Amino Acid and Biogenic Amines Profiling in Chronic Kidney Disease

Guillermo Gervasini
* ORCID logo ,
Zoraida Verde
ORCID logo ,
Luz María González
,
Celia Chicharro
,
Laura González-Rodríguez
,
Ana Fernández-Araque
ORCID logo ,
Sonia Mota-Zamorano
,
Alberto Pérez-Hernández
,
Virginio García-López
ORCID logo ,
Fernando Bandrés
,
Nicolás Roberto Robles
Version 1 : Received: 5 September 2023 / Approved: 6 September 2023 / Online: 7 September 2023 (11:24:56 CEST)

A peer-reviewed article of this Preprint also exists.

Gervasini, G.; Verde, Z.; González, L.M.; Chicharro, C.; González-Rodríguez, L.; Fernández-Araque, A.; Mota-Zamorano, S.; Cancho, B.; Pérez-Hernández, A.; García-López, V.; Bandrés, F.; Robles, N.R. Prognostic Significance of Amino Acid and Biogenic Amines Profiling in Chronic Kidney Disease. Biomedicines 2023, 11, 2775. Gervasini, G.; Verde, Z.; González, L.M.; Chicharro, C.; González-Rodríguez, L.; Fernández-Araque, A.; Mota-Zamorano, S.; Cancho, B.; Pérez-Hernández, A.; García-López, V.; Bandrés, F.; Robles, N.R. Prognostic Significance of Amino Acid and Biogenic Amines Profiling in Chronic Kidney Disease. Biomedicines 2023, 11, 2775.

Abstract

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by LC-MS/MS to determine a metabolic profile of 28 aminoacids (AA) and biogenic amines to test their value as markers of CKD risk and progression. The Kynurenine/Tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient=-0.731, P<0.0001). Models created with Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) containing the metabolic signature showed high goodness of fit and predictability for controls/CKD (R2X:0.73;R2Y:0.92;Q2:0.92) and lower for CDK/ESKD (R2X:0.56;R2Y:0.59;Q2:0.55). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD or CKD/ESKD groups were citrulline (1.67) and tryptophan (1.59), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (P<0.0001), and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (P<0.0001). Plasma concentrations of AA and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

Keywords

Chronic kidney disease; End-stage kidney disease; amino acids; metabolites

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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