title: Hypertensive patients exhibit an altered metabolism. A specific metabolite signature in urine is able to predict albuminuria progression.
abstract: Hypertension (HTN) 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 subgroup 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 5 years to investigate the evolution of albuminuria. Patients were classified as: (1) patients with persistent normoalbuminuria; (2) patients developing de novo albuminuria; and (3) patients with maintained albuminuria. At the end of follow-up, urine from 30 nonhypertensive 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 HTN 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 guanidinoacetate, 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.
authors.affiliation: Departamento de Inmunologia, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Calero
authors.affiliation: Departamento de Inmunologia, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martin-Lorenzo
authors.affiliation: Departamento de Inmunologia, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Martínez
authors.affiliation: Laboratorio de Fisiopatologia Vascular, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baldan-Martin
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i+12, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto Pluridisciplinar, Universidad Complutense de Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Ruiz-Hurtado
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i+12, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Julian
authors.initials: J
authors.lastname: Segura
authors.affiliation: Laboratorio de Fisiopatologia Vascular, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cuesta
authors.affiliation: Laboratorio de Fisiopatologia Vascular, Hospital Nacional de Paraplejicos SESCAM, Toledo, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Barderas
authors.affiliation: Unidad de Hipertension, Instituto de Investigacion i+12, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: ruilope@ad-hocbox.com.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruilope
authors.affiliation: Departamento de Inmunologia, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain; Departamento de Bioquimica y Biologia Molecular I, Universidad Complutense de Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vivanco
authors.affiliation: Departamento de Inmunologia, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain. Electronic address: galvarez@fjd.es.
authors.forename: Gloria
authors.initials: G
authors.lastname: Alvarez-Llamas
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine*; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D012084:Renin-Angiotensin System