Urinary Metabolic Signature of Primary Aldosteronism: Gender and Subtype-Specific Alterations.

PURPOSE: The current clinical investigation for primary aldosteronism (PA) diagnosis requires complex expensive tests from the initial suspicion to the final subtype classification, including invasive approaches; therefore, appropriate markers for subtype definition are greatly desirable. The present study performed a metabolomics analysis to further examine specific molecular signatures of PA urines EXPERIMENTAL DESIGN: : The study considered PA subtype and gender-related differences using two orthogonal advanced UHPLC-MS metabolomics approaches. We investigated patients with essential hypertension (n = 36) and PA (n = 50) who were referred to the outpatient hypertension clinic and included matched healthy subjects (n = 10).

RESULTS: We identified statistically significant changes (p<0.05 ANOVA, Fc>1.5) of metabolites involved in central carbon, energy and nitrogen metabolism, especially purine and pyrimidine nucleosides and precursors, and free amino acids. PLS-DA interpretation provided strong evidence of a disease-specific metabolic pattern with dAMP, diiodothyronine and 5-methoxytryptophan as leading factors, and a sex-specific metabolic pattern associated with orotidine 5-phosphate, N-acetylalanine, hydroxyproline and cysteine. The results were verified using an independent sample set, which confirmed the identification of specific signatures.

CONCLUSIONS AND CLINICAL RELEVANCE: Metabolomics was used to identify low molecular weight molecular markers of PA, which paves the way for follow-up validation studies in larger cohorts. This article is protected by copyright. All rights reserved.