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

Guenancia, Charles; Kahli, Abdelkader; Laurent, Gabriel; Hachet, Olivier; Malapert, Ghislain; Grosjean, Sandrine; Girard, Claude; Vergely, Catherine; Bouchot, Olivier

doi:10.1016/j.ijcard.2015.06.012

Cited by 43 publications

(40 citation statements)

References 36 publications

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“…10 In two recent analyses of patients undergoing coronary artery bypass graft surgery, preoperative elevated GDF-15 was associated with postoperative AKI. 11,12 Our study supports and extends the findings of these previous studies by studying participants with CKD of various causes in two independent CKD cohorts. GDF-15 may be a novel biomarker to identify patients with CKD at the highest risk of CKD progression.…”

Section: Discussionsupporting

confidence: 88%

“…In this study of two independent, well characterized CKD cohorts, we found intrarenal GDF15 expression in the tubulointerstitial compartment of patients with CKD is reflected by circulating GDF-15 levels, which are significantly associated with disease progression, as defined by continuous decline of eGFR or reaching a composite end point of 30% decline in eGFR or progression to ESRD, independent of other risk factors for progression of kidney disease, including (15) 53 (14) 58 (15) 59 (16) 63 (13) 62 (12) 55 (11) 64 (12) 66 (12) 66 (12) Women, % 128 (15) 136 (22) 136 (20) 142 25133 20129 21134 20134 (19) 136 (20) eGFR 9 In a study of type 1 diabetic patients with nephropathy, elevated GDF-15 was associated with more rapid decline in eGFR but not progression to ESRD. 10 In two recent analyses of patients undergoing coronary artery bypass graft surgery, preoperative elevated GDF-15 was associated with postoperative AKI.…”

Section: Discussionmentioning

confidence: 79%

“…Covariates for adjustment were selected a priori on the basis of previous literature on potential confounders for the association of GDF-15 with study outcomes. 9,11,12 Nested models were used in order to progressively explore the confounding effects of demographic characteristics, measures of kidney function, comorbidity, and medication use. The first model included baseline age, sex, race (white, black, other), eGFR (log 2 -transformed), and urine albumin-to-creatinine ratio (log-transformed).…”

Section: Statistical Analysesmentioning

confidence: 99%

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Growth Differentiation Factor–15 and Risk of CKD Progression

Nair¹,

Robinson‐Cohen

Smith³

et al. 2017

JASN

150

133

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Growth differentiation factor-15 (GDF-15) is a member of the TGF- cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal transcript levels (=0.54, =0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45;=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; =0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal -related signaling pathways associated with CKD and CKD progression.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 79%

Section: Statistical Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Growth Differentiation Factor–15 and Risk of CKD Progression

Nair¹,

Robinson‐Cohen

Smith³

et al. 2017

JASN

150

133

View full text Add to dashboard Cite

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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Background: Vascular calcification is a common phenomenon in patients with chronic kidney disease and strongly associated with increased cardiovascular mortality. Vascular calcification is an active process mediated in part by inflammatory processes in vascular smooth muscle cells (VSMC). These could be modified by the insufficient removal of proinflammatory cytokines through conventional high-flux (HF) membranes. Recent trials demonstrated a reduction of inflammation in VSMC by use of dialysis membranes with a higher and steeper cut-off. These membranes caused significant albumin loss. Therefore, the effect of high retention Onset (HRO) dialysis membranes on vascular calcification and its implications in vitro was evaluated. Methods: In the PERCI II trial, 48 chronic dialysis patients were dialyzed using HF and HRO dialyzers and serum samples were collected. Calcifying VSMC were incubated with the serum samples. Calcification was determined using alizarin red staining (AZR) and determination of alkaline phosphatase (ALP) activity. Furthermore, apoptosis was evaluated, and release of matrix Gla protein (MGP), osteopontin (OPN) and growth differentiation factor 15 (GDF-15) were measured in cell supernatants. Results: Vascular calcification in vitro was significantly reduced by 24% (ALP) and 36% (AZR) after 4 weeks of HRO dialysis and by 33% (ALP) and 48% (AZR) after 12 weeks of dialysis using HRO membranes compared to HF dialysis. Apoptosis was significantly lower in the HRO group. The concentrations of MGP and OPN were significantly elevated after incubation with HF serum compared to HRO serum and healthy controls. Similarly, GDF-15 release in the supernatant was elevated after incubation with HF serum, an effect significantly ameliorated after treatment with HRO medium. Conclusions: Expanded haemodialysis therapy reduces the pro-calcific potential of serum from dialysis patients in vitro. With a markedly reduced albumin filtration compared to high cut-off dialysis, use of the HRO dialyzers may possibly provide a treatment option for chronic dialysis patients to reduce the progression of vascular calcification.

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“…GDF-15 is associated with NT-proBNP and cTnT levels at presentation in those myocardial infarction patients33. Pre-operative GDF-15 plasma levels are also associated with post-operative AKI in CABG patients39. GDF-15 even improved risk stratification using the EuroSCORE before cardiac surgery2.…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of growth differentiation factor-15 are associated with myocardial injury in patients undergoing off-pump coronary artery bypass grafting

Yuan

et al. 2016

Sci Rep

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Growth differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiovascular diseases. We therefore aimed to investigate the role of GDF-15 in the occurrence of cardiac injury during off-pump coronary artery bypass grafting (OPCAB). 55 consecutive patients with coronary artery diseases were recruited in this prospective, observational study. All patients were operated for OPCAB surgery. Serial blood samples were collected preoperatively, 12 hours and 36 hours after surgery. GDF-15, together with C-reactive protein, cardiac troponin I, creatine kinase MB and N-terminal pro B-type natriuretic peptide levels in plasma were measured at each time-point. GDF-15 levels increased significantly at 12 hours after surgery, attaining nearly 2.5 times the baseline levels (p < 0.001). Postoperative GDF-15 levels correlated positively with cTnI (p = 0.003) and EuroSCORE II (p = 0.013). According to the ROC curves, postoperative plasma GDF-15 was found to be the best biomarker to predict perioperative cardiac injury, compared with cTnI, CK-MB and EuroSCORE II. Circulating GDF-15 is a promising novel biomarker for identifying perioperative myocardial injury in patients undergoing OPCAB.

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

Cited by 43 publications

References 36 publications

Growth Differentiation Factor–15 and Risk of CKD Progression

Growth Differentiation Factor–15 and Risk of CKD Progression

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

Plasma levels of growth differentiation factor-15 are associated with myocardial injury in patients undergoing off-pump coronary artery bypass grafting

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