Abstract: TH-PO475

Growth Differentiation Factor-15, Galectin-3, and Soluble ST-2 and Risk of Mortality and Cardiovascular Disease in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Tuegel, Courtney, University of Washington, Seattle, Washington, United States
  • Himmelfarb, Jonathan, University of Washington, Seattle, Washington, United States
  • Ju, Wenjun, University of Michigan, Ann Arbor, Michigan, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Robinson-Cohen, Cassianne, University of Washington, Seattle, Washington, United States
  • Steigerwalt, Susan P., University of Michigan, Ann Arbor, Michigan, United States
  • Bansal, Nisha, University of Washington, Seattle, Washington, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Bhat, Zeenat Yousuf, University of Michigan, Ann Arbor, Michigan, United States
  • Bellovich, Keith A., University of Michigan, Ann Arbor, Michigan, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
  • Brosius, Frank C., University of Michigan, Ann Arbor, Michigan, United States
  • Gadegbeku, Crystal A., University of Michigan, Ann Arbor, Michigan, United States
  • Gipson, Debbie S., University of Michigan, Ann Arbor, Michigan, United States
  • Hawkins, Jennifer Joyce, University of Michigan, Ann Arbor, Michigan, United States
Background

Novel pathways may explain the excess risk of cardiovascular disease (CVD) in the chronic kidney disease (CKD) population. Growth differentiation factor-15 (GDF-15), galectin-3 (gal-3), and soluble ST-2 (sST-2) are biomarkers of inflammation, cardiac remodeling, and fibrosis that may reflect pathways promoting CVD in CKD.

Methods

We pooled CKD participants in the cohorts Seattle Kidney Study and Clinical Phenotyping and Resource Biobank Study. GDF-15, gal-3 and sST-2 were measured at baseline. Outcomes were physician-adjudicated heart failure (HF) events, atherosclerotic CVD events (myocardial infarction or cerebrovascular accident), and mortality. Cox proportional hazards were used to test associations of biomarker levels with each outcome, adjusting for demographics, CVD risk factors, and renal function.

Results

Among 883 participants, the mean eGFR was 49 mL/min per 1.73 m2. Over median follow up of 3.10 years, there were 98 deaths (3.3%/year), 41 HF events (1.42%/year), and 29 atherosclerotic CVD events (1%/year). After adjusting for confounders, higher GDF-15, gal-3, and sST-2 levels were all independently associated with increased mortality (Table). Higher GDF-15 also associated with increased risk for HF and there was a trend for a similar association with sST-2. There were no statistically significant associations between GDF-15, gal-3, or sST-2 and risk of atherosclerotic CVD.

Conclusion

In adults with CKD, higher GDF-15, gal-3, and sST-2 are associated with increased risk of mortality. Elevated GDF-15 and sST-2 are also associated with increased risk of HF. The pathways of inflammation, cardiac remodeling, and fibrosis represented by these biomarkers may be important in the pathogenesis of CVD in those with CKD.

Funding

  • NIDDK Support