Growth Differentiation Factor-15 (GDF-15) Levels Are Associated with Cardiac and Renal Injury in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass

Abstract

ObjectiveGrowth 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).MethodsFive 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.ResultsPlasma 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.ConclusionsDuring cardiac surgery associated with CPB, GDF-15 levels increased substantially and were associated with markers of cardiac injury and renal dysfunction.

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

“…It is known that compared with OFP cardiac surgery, ONP is associated with an increase in both systemic inflammation and oxidative stress induced by ischemia-reperfusion injury [32,33]. In a previous study, we reported that a massive systemic release of free-radicals occurred following the removal of the cross-clamp during the CPB procedure [17]. In fact, during CPB, several factors (operative trauma, embolism, the contact of blood components with the artificial surface of the circuit, cardioplegic techniques and allogenic blood transfusion) stimulate pro-inflammatory mediators that activate leukocytes, vascular endothelial cells, and platelets.…”

“…Moreover, GDF-15 may also help to identify individuals at a high risk of developing chronic kidney disease (CKD), and has even been identified as an independent marker of mortality in this disease [16]. In a recent study, we identified a strong association between GDF-15 levels and renal function impairment [17].…”

Expanded Haemodialysis Therapy of Chronic Haemodialysis Patients Prevents Calcification and Apoptosis of Vascular Smooth Muscle Cells in vitro

“…GDF-15 has been introduced as a biomarker for cardiovascular events and ­cardiovascular risk stratification [42-44] and several vascular diseases including STEMI [42], coronary artery disease [43, 45], stroke [46] as well as renal and cardiac damage in general [47-49]. In addition to its value as a surrogate parameter, an active role in atherosclerosis and other vascular pathologies has been suggested [50, 51].…”

β2-Microglobulin and TIMP1 Are Linked Together in Cardiorenal Remodeling and Failure

“…Instead, when both heart and renal failure occur together, it is important to have biomarkers, just like b2M and TIMP1, able to risk-stratify patients by looking at both their cardiac and renal aspects. Of course, the clinical use of b2M and TIMP1 is not less important, in addition to BNP and other novel biomarkers of cardiorenal remodeling and inflammation, such as GDF 15 [25], in the differentiation between physiological and pathological cardiac remodeling. Finally, the results of our study might be tested for and extended to all cardiorenal syndrome subtypes.…”