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

Proteomics Clin Appl. 2019 Jul;13(4):e1800049. doi: 10.1002/prca.201800049. Epub 2019 Jan 4.


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 performs 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. Patients with essential hypertension (n = 36) and PA (n = 50) who were referred to the outpatient hypertension clinic and matched healthy subjects (n = 10) are investigated.

Results: Statistically significant changes (p < 0.05 ANOVA, Fc > 1.5) of metabolites involved in central carbon, energy, and nitrogen metabolism are identified, especially purine and pyrimidine nucleosides and precursors, and free amino acids. PLS-DA interpretation provides 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 are verified using an independent sample set, which confirms the identification of specific signatures.

Conclusions and clinical relevance: Metabolomics is used to identify low molecular weight molecular markers of PA, which paves the way for follow-up validation studies in larger cohorts.

Keywords: aldosterone-producing adenoma; aldosterone-to-renin ratio; hypertension; primary aldosteronism; urinary metabolomics.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / urine
  • Essential Hypertension / urine*
  • Female
  • Humans
  • Hyperaldosteronism / urine*
  • Male
  • Metabolomics
  • Middle Aged
  • Sex Characteristics*


  • Biomarkers