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Title: Prognostic significance of amino acid and biogenic amines profiling in chronic kidney disease
Authors: Gervasini Rodríguez, Guillermo
Verde Rello, Zoraida
González García, Luz María
Chicharro Miguel, Celia
González Rodríguez, Laura
Fernández Araque, Ana María
Mota Zamorano, Sonia
Cancho Castellano, Bárbara
Pérez Hernández, Alberto
García López, Virginio
Bandrés Moya, Fernando
Robles Pérez-Monteoliva, Nicolás Roberto
Keywords: Aminoácidos;Enfermedad renal crónica;Enfermedad renal terminal;Metabolitos;Amino acids;Chronic kidney disease;End-stage kidney disease;Metabolites
Issue Date: 2023
Publisher: MDPI
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 liquid chromatography with tandem mass spectrometry (LC-MS/MS) to determine a metabolic profile of 28 amino acids (AAs) 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 a high goodness of fit and predictability for controls/CKD (R2X:0.73:R2Y:0.92:Q2:0.92, p < 0.0001) and lower values for CKD/ESKD (R2X:0.56:R2Y:0.59:Q2:0.55, p < 0.0001). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD and CKD/ESKD groups were citrulline (1.63) and tryptophan (1.47), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved the 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 AAs and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.
DOI: 10.3390/biomedicines11102775
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