GDF-15, Galectin 3, Soluble ST2, and Risk of Mortality and Cardiovascular Events in CKD.

Tuegel C, Katz R, Alam M, Bhat Z, Bellovich K, de Boer I, Brosius F, Gadegbeku C, Gipson D, Hawkins J, Himmelfarb J, Ju W, Kestenbaum B, Kretzler M, Robinson-Cohen C, Steigerwalt S, Bansal N
Am J Kidney Dis. 2018 72 (4): 519-528

PMID: 29866459 · PMCID: PMC6153047 · DOI:10.1053/j.ajkd.2018.03.025

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±19mL/min/1.73m. 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.

Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

MeSH Terms (24)

Adult Aged Age Factors Biomarkers Cardiovascular Diseases Cause of Death Cohort Studies Comorbidity Female Galectin 3 Growth Differentiation Factor 15 Humans Interleukin-1 Receptor-Like 1 Protein Kaplan-Meier Estimate Male Middle Aged Prognosis Proportional Hazards Models Renal Insufficiency, Chronic Retrospective Studies Risk Assessment Severity of Illness Index Sex Factors Survival Analysis

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