Hypertensive Patients Exhibit an Altered Metabolism. a Specific Metabolite Signature in Urine is Able to Predict Albuminuria Progression

Abstract Hypertension is increasing in prevalence, and albuminuria is a strong indicator of cardiovascular risk and renal damage progression. Despite blood-pressure control with chronic treatment, a relevant sub-group of patients develop albuminuria. However, the biological factors responsible for albuminuria development and progression are underexplored. We aimed to identify key metabolic targets and biological pathways involved in the negative progression of cardiovascular and renal damage in hypertensives undergoing chronic treatment. A series of 1533 patients were followed for five years to investigate the evolution of albuminuria. Patients were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. At the end of follow-up, urine from 30 non-hypertensive subjects (control group) and a representative cohort of 118 patients was collected for metabolomic analysis. Metabolic patterns of interest were identified in a first discovery phase by nuclear magnetic resonance and further confirmed by liquid chromatography-mass spectrometry. Metabolites corresponding to hypertension or albuminuria were measured in a prospective study carried out in 35 individuals still in normoalbuminuria, to evaluate their potential as predictors of albuminuria development. Nine metabolites were significantly altered, linking β-alanine metabolism, arginine and proline metabolism and tricarboxylic acid cycle. The prospective study revealed a panel composed of guanidoacetate, glutamate, and pantothenate which was able to predict development of albuminuria. These metabolic signatures open new possibilities in hypertensive therapy and cardiovascular risk control, providing prompt and more efficient intervention, particularly in patients with worse cardiovascular prognosis.