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

Courtney Tuegel, Ronit Katz, Mariam Alam, Zeenat Bhat, Keith Bellovich, Ian de Boer, Frank Brosius, Crystal Gadegbeku, Debbie Gipson, Jennifer Hawkins, Jonathan Himmelfarb, Wenjun Ju, Bryan Kestenbaum, Matthias Kretzler, Cassianne Robinson-Cohen, Susan Steigerwalt, Nisha Bansal

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)519-528
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume72
Issue number4
DOIs
StatePublished - Oct 2018
Externally publishedYes

Keywords

  • CKD
  • Growth differentiation factor 15 (GDF-15)
  • acute ischemic stroke
  • acute myocardial infarction (AMI)
  • atherosclerotic CVD
  • cardiac biomarker
  • cardiovascular disease (CVD)
  • galectin 3 (Gal-3)
  • heart failure (HF)
  • mortality
  • soluble ST2 (sST2)

ASJC Scopus subject areas

  • Nephrology

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