TY - JOUR
T1 - Markers of kidney tubule function and risk of cardiovascular disease events and mortality in the SPRINT trial
AU - Garimella, Pranav S.
AU - Lee, Alexandra K.
AU - Ambrosius, Walter T.
AU - Bhatt, Udayan
AU - Cheung, Alfred K.
AU - Chonchol, Michel
AU - Craven, Timothy
AU - Hawfield, Amret T.
AU - Jotwani, Vasantha
AU - Killeen, Anthony
AU - Punzi, Henry
AU - Sarnak, Mark J.
AU - Wall, Barry M.
AU - Ix, Joachim H.
AU - Shlipak, Michael G.
N1 - Publisher Copyright:
© 2019 Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Aims: 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). Methods and results: 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. Conclusion: Among non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.
AB - Aims: 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). Methods and results: 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. Conclusion: Among non-diabetic persons with CKD, biomarkers of tubular function are associated with CVD events and mortality independent of glomerular function and albuminuria.
KW - Alpha-1 microglobulin
KW - Beta-2 microglobulin
KW - Biomarkers
KW - Cardiovascular disease
KW - Chronic kidney disease
KW - Tubular function
KW - Uromodulin
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U2 - 10.1093/eurheartj/ehz392
DO - 10.1093/eurheartj/ehz392
M3 - Article
C2 - 31257404
AN - SCOPUS:85074142006
SN - 0195-668X
VL - 40
SP - 3486
EP - 3493
JO - European heart journal
JF - European heart journal
IS - 42
ER -