Growth differentiation factor-15 (GDF-15) levels are associated with cardiac and renal injury in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

PLoS One. 2014 Aug 29;9(8):e105759. doi: 10.1371/journal.pone.0105759. eCollection 2014.

Abstract

Objective: Growth differentiation factor-15 (GDF-15) has been identified as a strong marker of cardiovascular disease; however, no data are available concerning the role of GDF-15 in the occurrence of organ dysfunction during coronary artery bypass grafting (CABG) associated with cardiopulmonary bypass (CPB).

Methods: Five arterial blood samples were taken sequentially in 34 patients from anesthesia induction (IND) until 24 h after arrival at the intensive care unit (ICU). Plasma levels of GDF-15, follistatin-like 1 (FLST1), myeloperoxidases (MPO), hydroperoxides and plasma antioxidant status (PAS) were measured at each time-point. Markers of cardiac (cardiac-troponin I, cTnI) and renal dysfunction (neutrophil gelatinase-associated lipocalin, NGAL) and other classical biological factors and clinical data were measured.

Results: Plasma GDF-15 levels increased gradually during and after surgery, reaching nearly three times the IND levels in the ICU (3,075±284 ng/L vs. 1,061±90 ng/L, p<0.001). Plasma MPO levels increased dramatically during surgery, attaining their highest level after unclamping (UNCLAMP) (49±11 ng/mL vs. 1,679±153 ng/mL, p<0.001) while PAS significantly decreased between IND and UNCLAMP (p<0.05), confirming the high oxidative status induced by this surgical procedure. ICU levels of GDF-15 correlated positively with cTnI and NGAL (p = 0.006 and p = 0.036, respectively), and also with hemoglobin and estimated glomerular filtration rate (eGFR). Among all the post-operative biomarkers available, only eGFR, NGAL and GDF-15 measured at ICU arrival were significantly associated with the onset of acute kidney injury (AKI). Patients with a EuroSCORE >3 were shown to have higher GDF-15 levels.

Conclusions: During cardiac surgery associated with CPB, GDF-15 levels increased substantially and were associated with markers of cardiac injury and renal dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / etiology
  • Acute-Phase Proteins
  • Aged
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Cardiopulmonary Bypass / adverse effects
  • Cardiopulmonary Bypass / methods*
  • Coronary Artery Bypass / adverse effects
  • Coronary Artery Bypass / methods*
  • Female
  • Follistatin-Related Proteins / blood
  • Growth Differentiation Factor 15 / blood*
  • Heart Diseases / blood*
  • Heart Diseases / diagnosis
  • Heart Diseases / etiology
  • Humans
  • Hydrogen Peroxide / blood
  • Intensive Care Units
  • Lipocalin-2
  • Lipocalins / blood
  • Male
  • Middle Aged
  • Peroxidase / blood
  • Postoperative Complications / blood
  • Postoperative Complications / diagnosis
  • Postoperative Complications / etiology
  • Predictive Value of Tests
  • Proto-Oncogene Proteins / blood
  • Troponin I / blood

Substances

  • Acute-Phase Proteins
  • Antioxidants
  • Biomarkers
  • Follistatin-Related Proteins
  • Growth Differentiation Factor 15
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Troponin I
  • FSTL1 protein, human
  • Hydrogen Peroxide
  • Peroxidase

Grants and funding

This work was supported by grants from the French Ministry of Research, from the Institut National de la Santé et de la Recherche Médicale (INSERM)and from the Regional Council of Burgundy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.