Markers of kidney tubule function and risk of cardiovascular disease events and mortality in the SPRINT trial.
Alpha-1 microglobulin
Beta-2 microglobulin
Biomarkers
Cardiovascular disease
Chronic kidney disease
Tubular function
Uromodulin
Journal
European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
04
02
2019
revised:
11
04
2019
accepted:
21
05
2019
pubmed:
2
7
2019
medline:
21
10
2020
entrez:
2
7
2019
Statut:
ppublish
Résumé
Biomarkers of kidney tubule injury, inflammation and fibrosis have been studied extensively and established as risk markers of adverse kidney and cardiovascular disease (CVD) outcomes. However, associations of markers of kidney tubular function with adverse clinical events have not been well studied, especially in persons with chronic kidney disease (CKD). Using a sample of 2377 persons with CKD at the baseline Systolic Blood Pressure Intervention Trial (SPRINT) visit, we evaluated the association of three urine tubular function markers, alpha-1 microglobulin (α1m), beta-2 microglobulin (β2m), and uromodulin, with a composite CVD endpoint (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes) and mortality using Cox proportional hazards regression, adjusted for baseline estimated glomerular filtration rate (eGFR), albuminuria, and CVD risk factors. In unadjusted analysis, over a median follow-up of 3.8 years, α1m and β2m had positive associations with composite CVD events and mortality, whereas uromodulin had an inverse association with risk for both outcomes. In multivariable analysis including eGFR and albuminuria, a two-fold higher baseline concentration of α1m was associated with higher risk of CVD [hazard ratio (HR) 1.25; 95% confidence interval (CI): 1.10-1.45] and mortality (HR 1.25; 95% CI: 1.10-1.46), whereas β2m had no association with either outcome. A two-fold higher uromodulin concentration was associated with lower CVD risk (HR 0.79; 95% CI: 0.68-0.90) but not mortality (HR 0.86; 95% CI: 0.73-1.01) after adjusting for similar confounders. Among non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.
Identifiants
pubmed: 31257404
pii: 5525357
doi: 10.1093/eurheartj/ehz392
pmc: PMC6837159
doi:
Substances chimiques
Biomarkers
0
Uromodulin
0
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3486-3493Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK098234
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK114556
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002003
Pays : United States
Organisme : NIDDK NIH HHS
ID : K24 DK110427
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003142
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
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