Pre-operative growth differentiation factor 15 as a novel biomarker of acute kidney injury after cardiac bypass surgery.

BACKGROUND: Pre-operative GDF-15 plasma levels significantly improve the prognostic value of the EuroSCORE for mortality after cardiac surgery. However, despite the strong correlation between GDF-15 and renal function, no data are available regarding the potential interest of pre-operative GDF-15 levels to improve the prediction of acute kidney injury (AKI) after cardiac artery bypass graft (CABG) surgery. METHODS: All patients operated on by 2 surgeons for CABG surgery at our university hospital from September 2011 to March 2013 were screened for participation in this prospective, observational study. EXCLUSION CRITERIA: age <18years or >80years, previous atrial fibrillation/flutter, previous severe renal failure, previous cardiac surgery, emergency surgery. AKI was defined according to KDIGO criteria. GDF-15 levels in plasma were measured before induction and 12h after surgery. RESULTS: 134 patients were included in this study. 42 (31%) developed post-operative AKI. AKI patients had a significantly higher pre-operative log-GDF-15 level (OR=3.64; 95% CI=1.41-9.40, p=0.008), a lower pre-operative eGFR (OR=0.98; 95% CI=0.96-0.99; p=0.026), and most often underwent on-pump surgery (OR=2.60; 95% CI=1.14-5.96, p=0.024). On ROC curves, GDF-15 before induction was found to be the best pre-operative biomarker to predict AKI (AUC=0.83; CI=0.75-0.89), compared with eGFR (AUC=0.67; 95% CI=0.59-0.75), p=0.003 and NT-proBNP (AUC=0.62; CI=0.51-0.72), p<0.001. Pre-operative GDF-15 was also significantly better than the EuroSCORE in predicting AKI (AUC 0.62, 95% CI=0.54-0.70), p<0.001. CONCLUSIONS: Pre-operative GDF-15 plasma levels are associated with post-operative AKI in CABG patients. If confirmed in larger cohorts, pre-operative GDF-15 may be of value to improve pre-operative risk stratification among candidates for surgery.

Low Circulating Levels of Growth Differentiation Factor-15 Before Coronary Artery Bypass Surgery May Predict Postoperative Atrial Fibrillation.

OBJECTIVES: To assess the role of growth differentiation factor-15 (GDF-15) as a potential new predictor of postoperative atrial fibrillation (POAF) after off-pump (OFP) and on-pump (ONP) coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, single-center, observational study. SETTING: University teaching hospital. PARTICIPANTS: The first 50 patients planned for OFP surgery and the first 50 patients planned for ONP surgery among patients referred for CABG with the following exclusion criteria: age<18 or>80 years, previous atrial fibrillation/flutter, previous treatment with amiodarone, previous cardiac surgery, and emergency surgery. INTERVENTIONS: Included patients were equipped with long-duration (7 days) Holter-ECG monitoring. MEASUREMENTS AND MAIN RESULTS: POAF was defined as an AF episode lasting>30 seconds. All patients underwent preoperative echocardiography to assess left ventricular ejection fraction and left atrial diameter. GDF-15 levels were assessed after induction of anesthesia and 12 hours after arrival at the intensive care unit. Among the 100 patients, 34 (34%) developed POAF. In Cox multivariate regression analysis, the EuroSCORE, left atrial diameter>45 mm, and low GDF-15 levels at induction were associated independently with the onset of POAF. In contrast, preoperative NT-proBNP levels did not predict POAF. The use of ONP surgery was not associated with a higher incidence of POAF, even though baseline and follow-up characteristics in ONP and OFP patients were identical. CONCLUSIONS: In patients with no history of AF, a low plasma level of GDF-15 before CABG surgery was a strong independent predictor of POAF. Moreover, preoperative plasma GDF-15 levels added an incremental predictive value to classic risk factors of POAF.

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

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.