Growth Differentiation Factor-15 Is a Predictor of Mortality in Critically Ill Patients with Sepsis

Buendgens, Lukas; Yagmur, Eray; Bruensing, Jan; Herbers, Ulf; Baeck, Christer; Trautwein, Christian; Koch, Alexander; Tacke, Frank

doi:10.1155/2017/5271203

Cited by 69 publications

(63 citation statements)

References 38 publications

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“…Using a sandwich ELISA of the same manufacturer, studies have reported median plasma GDF-15 levels of 309 ng/L (IQR 275-411) for healthy individuals and 427 ng/L (IQR 344-626) in obese patients, 18 or median levels of 1097 ng/L and 5753 ng/L for healthy and critically ill patients. 19 Regarding malignant disease, GDF-15 levels were determined with a mean value of 746 ng/L in controls vs 1075 ng/L in colorectal cancer patients. 20 GDF-15 levels within this study correspond well to these data.…”

Section: Gdf-15 Levels In Comparisonsupporting

confidence: 88%

GDF‐15 in solid vs non‐solid treatment‐naïve malignancies

Arfsten

Cho

Freitag

et al. 2019

Eur J Clin Investigation

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AimGDF‐15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF‐15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF‐15 to other cardiac biomarkers and the general association of GDF‐15 on prognosis in an unselected cohort of treatment‐naïve cancer patients.MethodsWe prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF‐15 concentrations were determined alongside other cardiac and routine laboratory markers. All‐cause mortality was defined as primary endpoint.ResultsGDF‐15 levels were 338 ng/L (IQR:205‐534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF‐15 [435 ng/L (IQR:279‐614) vs 266 ng/L (IQR:175‐427), P < .001]. GDF‐15 correlated positively with inflammatory status reflected by CRP, SAA and IL‐6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NT‐proBNP, hsTnT, MR‐proADM and CT‐proET‐1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF‐15 was significantly associated with all‐cause mortality after multivariate adjustment [adj.HR for ln(GDF‐15) 1.78, 95%CI:1.47‐2.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF‐15 with outcome in myelodysplastic and myeloproliferative disease.ConclusionsElevated plasma GDF‐15 is associated with progressing disease severity and poor prognosis in solid tumours of treatment‐naïve cancer patients. GDF‐15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF‐15 represents a promising target for our pathophysiologic understanding in cardio‐oncology linking conditions of both cardiac and neoplastic disease.

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Section: Gdf-15 Levels In Comparisonsupporting

confidence: 88%

GDF‐15 in solid vs non‐solid treatment‐naïve malignancies

Arfsten

Cho

Freitag

et al. 2019

Eur J Clin Investigation

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“…Informed consent was obtained from each participant or their spouse. The patients were categorized as sepsis and non‐sepsis according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis‐3), and were treated following the current guidelines for treatment of sepsis (Surviving Sepsis Campaign) . As a healthy control group, we analyzed blood donors with normal blood counts, normal values of liver enzymes and a negative serology for viral hepatitis and HIV …”

Section: Methodsmentioning

confidence: 99%

Clinical relevance of copeptin plasma levels as a biomarker of disease severity and mortality in critically ill patients

Koch

Yagmur²,

Hoss

et al. 2018

Clinical Laboratory Analysis

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“…Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor β-superfamily and is widely expressed in adult tissues [5]. Elevated GDF-15 levels are associated with chronic inflammation, oxidative stress, and tissue injury [6].…”

Section: Introductionmentioning

confidence: 99%

Association between Plasma Levels of Growth Differentiation Factor-15 and Renal Function in the Elderly: Korean Frailty and Aging Cohort Study

Kim

Won

et al. 2019

Kidney Blood Press Res

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Background/Aims: Growth differentiation factor-15 (GDF-15) expression has been reported to increase in response to tissue damage and has recently emerged as a useful biomarker for various diseases. Although emerging evidence supports the clinicopathological value of GDF-15 in renal impairment, few studies have analyzed it in the elderly. Thus, we conducted a cross-sectional study to investigate the association of plasma GDF-15 with renal function and the presence of chronic kidney disease (CKD) in community-dwelling elderly. Materials: The present study was based on the baseline data of the Korean Frailty and Aging Cohort Study (KFACS), a nationwide cohort study that began in 2016. Of the 1,559 participants assessed in the first year, 443 with available plasma GDF-15 data were enrolled in this study. We investigated the association of plasma GDF-15 levels with clinical and biochemical parameters. The study population was divided into two groups according to renal function (CKD and non-CKD groups) to investigate whether GDF-15 can determine the presence of renal dysfunction in the elderly. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA) kit. Results: In a simple regression analysis, the levels of plasma GDF-15 were negatively correlated with estimated glomerular filtration rate (eGFR; r = –0.383, p < 0.001). In multiple linear regression analysis, GDF-15 levels were still significantly correlated with eGFR, even after adjusting for other parameters (r = –0.259, p < 0.001). Plasma GDF-15 levels were significantly higher in the elderly with CKD than in those without CKD (2,364.025 ± 1,052.23 ng/L and 1,451.23 ± 835.79 ng/L, respectively; p < 0.001). The optimal cut-off value of plasma GDF-15 for detecting the presence of CKD was 1,699.4 ng/L (76.5% sensitivity and 76.0% specificity), as determined by the receiver operating characteristic curve. The area under the curve was 0.793 ± 0.033 (95% CI 0.729–0.857, p < 0.001). Conclusion: Plasma GDF-15 levels were negatively associated with eGFR and were significantly increased in the elderly with CKD. Our results suggested that plasma GDF-15 might be a useful marker for discriminating renal impairment in the elderly. Further large and prospective outcome studies of extended duration are needed.

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Growth Differentiation Factor-15 Is a Predictor of Mortality in Critically Ill Patients with Sepsis

Cited by 69 publications

References 38 publications

GDF‐15 in solid vs non‐solid treatment‐naïve malignancies

GDF‐15 in solid vs non‐solid treatment‐naïve malignancies

Clinical relevance of copeptin plasma levels as a biomarker of disease severity and mortality in critically ill patients

Association between Plasma Levels of Growth Differentiation Factor-15 and Renal Function in the Elderly: Korean Frailty and Aging Cohort Study

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