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Thürmann, L.* ; Seegebarth, A.* ; von Berg, A.* ; Berdel, D.* ; Koletzko, S.* ; Heinrich, J.* ; Schikowski, T.* ; Lehmann, I.* ; Standl, M. ; Trump, S.*

Distinct urinary protein signatures in adolescent blood pressure phenotypes.

Circ. Res. 139:e328246 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The increasing prevalence of childhood hypertension constitutes an important risk factor for cardiovascular disease (CVD), contributing to long-term morbidity and mortality and imposing substantial healthcare costs.1 Among potential mechanisms, early-life immune activation, characterized by low-grade inflammatory and immune-cell responses, may contribute to endothelial dysfunction and vascular remodeling, initiating processes that predispose individuals to long-term cardiovascular sequelae. We recently reported transcriptional alterations indicative of cytotoxic (PRF1, GZMB, IL2RB) and inflammatory responses (IL1B, FOS) in blood from adolescents with elevated blood pressure (BP).2 This reflects circulating immune cell activation, but does not permit tissue-specific attribution. Urinary proteins, in contrast, provide a complementary downstream biological readout that may capture inflammatory signals at the circulation-vascular/renal interface, and thus may serve as noninvasive indicators of early target-organ-related processes.Given the distinct pathophysiological characteristics and CVD risk profiles of the BP subphenotypes3,4—isolated diastolic hypertension (IDH), isolated systolic hypertension, and combined systolic and diastolic hypertension (SDH)—we hypothesize that early-life BP-related immune activation is associated with endothelial dysfunction, and subphenotype-specific subclinical inflammation before the formal diagnosis of hypertension.IDH, recently defined as a distinct entity in the 2023 European Society of Hypertension guideline, remains insufficiently characterized in early life.3 It is more prevalent in adolescents than in adults and often underdiagnosed. Although its contribution to CVD sequelae remains inconclusive,3 IDH has been shown to predict chronic kidney disease risk,4 supporting the investigation of IDH during adolescence.We quantified 10 inflammatory protein markers (LEGENDplex Human Vascular Inflammation Panel 1-U, BioLegend) in spot urine samples from 15-year-old adolescents of the GINIplus birth cohort study (n=3199; ethical approvals: Bavarian Board of Physicians: 10090; Board of Physicians of North-Rhine-Westphalia: 2010424/2015491; Figure [A]). Participants reporting physician-diagnosed hypertension at the 20-year follow-up or a urinary tract infection within 4 weeks before sampling were excluded. After restricting analyses to individuals with complete BP, protein, and confounder data, 1502 participants remained (Figure [A] and [B]). BP was measured twice on the right arm, and the mean of the 2 valid measurements was used.2 Elevated BP subphenotypes, isolated systolic hypertension, IDH, SDH (≥P95th), and normotension (
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Letter to the Editor
Schlagwörter Adult ; Blood Pressure ; Humans ; Phenotype ; Urine
ISSN (print) / ISBN 0009-7330
e-ISSN 1524-4571
Zeitschrift Circulation Research
Quellenangaben Band: 139, Heft: 6, Seiten: , Artikelnummer: e328246 Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Förderungen LMU Munich, TU Munich
Research Institute at Marien-Hospital Wesel/EVK Dusseldorf
HMGU
Nestle
Mead Johnson
The 7th Framework Program: MeDALL project
Commission of the European Communities
Federal Ministry for Environment (IUF)
Federal Ministry for Education, Science, Research and Technology (BMBF)