TY - JOUR
T1 - GDF-15, Galectin 3, Soluble ST2, and Risk of Mortality and Cardiovascular Events in CKD
AU - Tuegel, Courtney
AU - Katz, Ronit
AU - Alam, Mariam
AU - Bhat, Zeenat
AU - Bellovich, Keith
AU - de Boer, Ian
AU - Brosius, Frank
AU - Gadegbeku, Crystal
AU - Gipson, Debbie
AU - Hawkins, Jennifer
AU - Himmelfarb, Jonathan
AU - Ju, Wenjun
AU - Kestenbaum, Bryan
AU - Kretzler, Matthias
AU - Robinson-Cohen, Cassianne
AU - Steigerwalt, Susan
AU - Bansal, Nisha
N1 - Publisher Copyright:
© 2018 National Kidney Foundation, Inc.
PY - 2018/10
Y1 - 2018/10
N2 - Rationale & Objective: Inflammation, cardiac remodeling, and fibrosis may explain in part the excess risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Growth differentiation factor 15 (GDF-15), galectin 3 (Gal-3), and soluble ST2 (sST2) are possible biomarkers of these pathways in patients with CKD. Study Design: Observational cohort study. Setting & Participants: Individuals with CKD enrolled in either of 2 multicenter CKD cohort studies: the Seattle Kidney Study or C-PROBE (Clinical Phenotyping and Resource Biobank Study). Exposures: Circulating GDF-15, Gal-3, and sST2 measured at baseline. Outcomes: Primary outcome was all-cause mortality. Secondary outcomes included hospitalization for physician-adjudicated heart failure and the atherosclerotic CVD events of myocardial infarction and cerebrovascular accident. Analytic Approach: Cox proportional hazards models used to test the association of each biomarker with each outcome, adjusting for demographics, CVD risk factors, and kidney function. Results: Among 883 participants, mean estimated glomerular filtration rate was 49 ± 19 mL/min/1.73 m2. Higher GDF-15 (adjusted HR [aHR] per 1-SD higher, 1.87; 95% CI, 1.53-2.29), Gal-3 (aHR per 1-SD higher, 1.51; 95% CI, 1.36-1.78), and sST2 (aHR per 1-SD higher, 1.36; 95% CI, 1.17-1.58) concentrations were significantly associated with mortality. Only GDF-15 level was also associated with heart failure events (HR per 1-SD higher, 1.56; 95% CI, 1.12-2.16). There were no detectable associations between GDF-15, Gal-3, or sST2 concentrations and atherosclerotic CVD events. Limitations: Event rates for heart failure and atherosclerotic CVD were low. Conclusions: Adults with CKD and higher circulating GDF-15, Gal-3, and sST2 concentrations experienced greater mortality. Elevated GDF-15 concentration was also associated with an increased rate of heart failure. Further work is needed to elucidate the mechanisms linking these circulating biomarkers with CVD in patients with CKD.
AB - Rationale & Objective: Inflammation, cardiac remodeling, and fibrosis may explain in part the excess risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Growth differentiation factor 15 (GDF-15), galectin 3 (Gal-3), and soluble ST2 (sST2) are possible biomarkers of these pathways in patients with CKD. Study Design: Observational cohort study. Setting & Participants: Individuals with CKD enrolled in either of 2 multicenter CKD cohort studies: the Seattle Kidney Study or C-PROBE (Clinical Phenotyping and Resource Biobank Study). Exposures: Circulating GDF-15, Gal-3, and sST2 measured at baseline. Outcomes: Primary outcome was all-cause mortality. Secondary outcomes included hospitalization for physician-adjudicated heart failure and the atherosclerotic CVD events of myocardial infarction and cerebrovascular accident. Analytic Approach: Cox proportional hazards models used to test the association of each biomarker with each outcome, adjusting for demographics, CVD risk factors, and kidney function. Results: Among 883 participants, mean estimated glomerular filtration rate was 49 ± 19 mL/min/1.73 m2. Higher GDF-15 (adjusted HR [aHR] per 1-SD higher, 1.87; 95% CI, 1.53-2.29), Gal-3 (aHR per 1-SD higher, 1.51; 95% CI, 1.36-1.78), and sST2 (aHR per 1-SD higher, 1.36; 95% CI, 1.17-1.58) concentrations were significantly associated with mortality. Only GDF-15 level was also associated with heart failure events (HR per 1-SD higher, 1.56; 95% CI, 1.12-2.16). There were no detectable associations between GDF-15, Gal-3, or sST2 concentrations and atherosclerotic CVD events. Limitations: Event rates for heart failure and atherosclerotic CVD were low. Conclusions: Adults with CKD and higher circulating GDF-15, Gal-3, and sST2 concentrations experienced greater mortality. Elevated GDF-15 concentration was also associated with an increased rate of heart failure. Further work is needed to elucidate the mechanisms linking these circulating biomarkers with CVD in patients with CKD.
KW - CKD
KW - Growth differentiation factor 15 (GDF-15)
KW - acute ischemic stroke
KW - acute myocardial infarction (AMI)
KW - atherosclerotic CVD
KW - cardiac biomarker
KW - cardiovascular disease (CVD)
KW - galectin 3 (Gal-3)
KW - heart failure (HF)
KW - mortality
KW - soluble ST2 (sST2)
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U2 - 10.1053/j.ajkd.2018.03.025
DO - 10.1053/j.ajkd.2018.03.025
M3 - Article
C2 - 29866459
AN - SCOPUS:85047800702
SN - 0272-6386
VL - 72
SP - 519
EP - 528
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 4
ER -