Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease.
Aged
Aged, 80 and over
Albuminuria
/ diagnosis
Antihypertensive Agents
/ administration & dosage
Biomarkers
/ urine
Blood Pressure
/ drug effects
Blood Pressure Determination
/ standards
Cardiovascular Diseases
/ epidemiology
Disease Progression
Female
Fibrosis
Glomerular Filtration Rate
/ physiology
Humans
Hypertension
/ drug therapy
Kidney Tubules
/ immunology
Male
Prognosis
Renal Insufficiency, Chronic
/ complications
Chitinase-3-like protein-1
Interleukin-18
Kidney injury
Urinary biomarkers
Journal
American journal of nephrology
ISSN: 1421-9670
Titre abrégé: Am J Nephrol
Pays: Switzerland
ID NLM: 8109361
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
12
2018
accepted:
11
02
2019
pubmed:
3
4
2019
medline:
7
7
2020
entrez:
3
4
2019
Statut:
ppublish
Résumé
Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01-1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02-1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.
Sections du résumé
BACKGROUND
Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD.
METHODS
We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality.
RESULTS
At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01-1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02-1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm.
CONCLUSIONS
Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.
Identifiants
pubmed: 30939472
pii: 000499531
doi: 10.1159/000499531
pmc: PMC6491265
mid: NIHMS1018991
doi:
Substances chimiques
Antihypertensive Agents
0
Biomarkers
0
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
346-355Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000445
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK098234
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000064
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000075
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079626
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000093
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000050
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Organisme : NIDDK NIH HHS
ID : K24 DK110427
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024134
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900048C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
Organisme : NIDDK NIH HHS
ID : K23 DK109868
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900040C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900046C
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103337
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001064
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025752
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025771
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900049C
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268200900047C
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001427
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000073
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR025755
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000002
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002240
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000105
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 S. Karger AG, Basel.
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