Low Serum Levels of Soluble Receptor Activator of Nuclear Factor κ B Ligand (sRANKL) Are Associated with Metabolic Dysregulation and Predict Long-Term Mortality in Critically Ill Patients

Soluble receptor activator of nuclear factor κ B ligand (sRANKL) is a member of the tumor necrosis factor receptor superfamily, and therefore, involved in various inflammatory processes. The role of sRANKL in the course of bone remodeling via activation of osteoclasts as well as chronic disease progression has been described extensively. However, the potential functional importance of sRANKL in critically ill or septic patients remained unknown. Therefore, we measured sRANKL serum concentrations in 303 critically ill patients, including 203 patients with sepsis and 100 with non-sepsis critical illness. Results were compared to 99 healthy controls. Strikingly, in critically ill patients sRANKL serum levels were significantly decreased at intensive care unit (ICU) admission (p = 0.011) without differences between sepsis and non-sepsis patients. Inline, sRANKL was correlated with markers of metabolic dysregulation, such as pre-existing diabetes and various adipokines (e.g., adiponectin, leptin receptor). Importantly, overall mortality of critically ill patients in a three-year follow-up was significantly associated with decreased sRANKL serum concentrations at ICU admission (p = 0.038). Therefore, our study suggests sRANKL as a biomarker in critically ill patients which is associated with poor prognosis and overall survival beyond ICU stay.

Download Full-text

Regulation and Prognostic Relevance of Symmetric Dimethylarginine Serum Concentrations in Critical Illness and Sepsis

Mediators of Inflammation ◽

10.1155/2013/413826 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 14

Author(s):

Alexander Koch ◽

Ralf Weiskirchen ◽

Jan Bruensing ◽

Hanna Dückers ◽

Lukas Buendgens ◽

...

Keyword(s):

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Multiorgan Failure ◽

Microvascular Dysfunction ◽

Serum Levels ◽

Serum Concentrations ◽

Symmetric Dimethylarginine ◽

Term Survival ◽

Severity Scores

In systemic inflammation and sepsis, endothelial activation and microvascular dysfunction are characteristic features that promote multiorgan failure. As symmetric dimethylarginine (SDMA) impacts vascular tension and integrity via modulating nitric oxide (NO) pathways, we investigated circulating SDMA in critical illness and sepsis. 247 critically ill patients (160 with sepsis, 87 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 84 healthy controls. SDMA serum levels were significantly elevated in critically ill patients at admission to ICU compared to controls and remained stably elevated during the first week of ICU treatment. The highest SDMA levels were found in patients with sepsis. SDMA levels closely correlated with disease severity scores, biomarkers of inflammation, and organ failure (renal, hepatic, and circulatory). We identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival. Thus, the significant increase of circulating SDMA in critically ill patients indicates a potential pathogenic involvement in endothelial dysfunction during sepsis and may be useful for mortality risk stratification at the ICU.

Download Full-text

Low Myostatin Serum Levels Are Associated with Poor Outcome in Critically Ill Patients

Diagnostics ◽

10.3390/diagnostics10080574 ◽

2020 ◽

Vol 10 (8) ◽

pp. 574

Author(s):

Theresa H. Wirtz ◽

Sven H. Loosen ◽

Lukas Buendgens ◽

Berkan Kurt ◽

Samira Abu Jhaisha ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Cox Regression ◽

Muscle Growth ◽

Serum Levels ◽

Serum Concentrations ◽

Icu Patients ◽

Cox Regression Analysis ◽

Independent Prognostic Marker ◽

Unfavorable Clinical Outcome

Background: Growth differentiation factor 8, GDF-8 (Myostatin), is a protein released by myocytes inhibiting muscle growth and differentiation. Serum concentrations of Myostatin can predict poor survival in different chronic diseases, but its role in critical illness and sepsis is obscure. Our aim was to investigate Myostatin levels as a potential prognostic biomarker in critically ill patients with sepsis. Methods: We therefore measured Myostatin serum concentrations in 165 critically ill patients (106 with sepsis, 59 without sepsis) upon admission to the medical intensive care unit (ICU), in comparison to 14 healthy controls. Results: Myostatin levels were significantly decreased in ICU patients compared to controls but did not differ in patients with or without sepsis. However, Myostatin concentrations were significantly lower in patients requiring mechanical ventilation and indicated a trend towards dependency of intravenous vasopressors. Interestingly, we observed a negative correlation between Myostatin levels and markers of systemic inflammation. Strikingly, overall survival (OS) was significantly impaired in patients with low Myostatin levels in all critically ill patients. Low Myostatin levels at baseline turned out as an independent prognostic marker for OS in multivariate Cox-regression analysis (HR: 0.433, 95% CI: 0.211–0.889, p = 0.023). Conclusions: In summary, serum Myostatin concentrations are significantly decreased in critically ill patients and associated with disease severity. Low Myostatin levels also identify a subgroup of ICU patients that are more likely to face an unfavorable clinical outcome in terms of OS.

Download Full-text

Association between serum levels of interleukin-6 on ICU admission and subsequent outcomes in critically ill patients with acute kidney injury

BMC Nephrology ◽

10.1186/s12882-019-1265-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Takashi Shimazui ◽

Taka-aki Nakada ◽

Yoshihisa Tateishi ◽

Taku Oshima ◽

Tuerxun Aizimu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Interleukin 6 ◽

Kidney Injury ◽

Serum Levels ◽

Icu Admission

Download Full-text

Serum levels of the osteoprotegerin, receptor activator of nuclear factor κ-B ligand, metalloproteinase-1 (MMP-1) and tissue inhibitors of MMP-1 levels are increased in men 6 months after acute myocardial infarction

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2008.091 ◽

2008 ◽

Vol 46 (4) ◽

Cited By ~ 15

Author(s):

Antonios Halapas ◽

Achilleas Zacharoulis ◽

Stamatios Theocharis ◽

Apostolos Karavidas ◽

Dimitrios Korres ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Serum Levels ◽

Nuclear Factor ◽

Tissue Inhibitors ◽

Receptor Activator ◽

Nuclear Factor Κ B

Download Full-text

Changes in the serum levels of osteoprotegerin and soluble receptor activator for nuclear factor κB ligand after estrogen-progestogen therapy and their relationships with changes in bone mass in postmenopausal women

Menopause The Journal of The North American Menopause Society ◽

10.1097/gme.0b013e318133a153 ◽

2008 ◽

Vol 15 (2) ◽

pp. 357-362 ◽

Cited By ~ 13

Author(s):

Jung Gu Kim ◽

Jung Hwa Kim ◽

Dong Ock Lee ◽

Hoon Kim ◽

Ja Yeon Kim ◽

...

Keyword(s):

Bone Mass ◽

Postmenopausal Women ◽

Serum Levels ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Soluble Receptor ◽

Receptor Activator

Download Full-text

Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Could Provide Better Accuracy Than Creatinine in Predicting Acute Kidney Injury Development in Critically Ill Patients

Journal of Clinical Medicine ◽

10.3390/jcm10225379 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5379

Author(s):

Edison Jahaj ◽

Alice G. Vassiliou ◽

Maria Pratikaki ◽

Parisis Gallos ◽

Zafeiria Mastora ◽

...

Keyword(s):

Acute Kidney Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Kidney Injury ◽

Roc Curves ◽

Serum Levels ◽

Icu Admission ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Increased Risk ◽

Neutrophil Gelatinase

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development (n = 98) or not (n = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not (p < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002–1.008), p < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.

Download Full-text

Elevated Omentin Serum Levels Predict Long-Term Survival in Critically Ill Patients

Disease Markers ◽

10.1155/2016/3149243 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Mark Luedde ◽

Fabian Benz ◽

Jennifer Niedeggen ◽

Mihael Vucur ◽

Hans-Joerg Hippe ◽

...

Keyword(s):

Critical Illness ◽

Critically Ill ◽

Critically Ill Patients ◽

Serum Levels ◽

Healthy Controls ◽

Serum Concentrations ◽

Term Survival ◽

Icu Patients ◽

Icu Treatment

Introduction. Omentin, a recently described adipokine, was shown to be involved in the pathophysiology of inflammatory and infectious diseases. However, its role in critical illness and sepsis is currently unknown. Materials and Methods. Omentin serum concentrations were measured in 117 ICU-patients (84 with septic and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were compared with 50 healthy controls. Results. Omentin serum levels of critically ill patients at admission to the ICU or after 72 hours of ICU treatment were similar compared to healthy controls. Moreover, circulating omentin levels were independent of sepsis and etiology of critical illness. Notably, serum concentrations of omentin could not be linked to concentrations of inflammatory cytokines or routinely used sepsis markers. While serum levels of omentin were not predictive for short term survival during ICU treatment, low omentin concentrations were an independent predictor of patients’ overall survival. Omentin levels strongly correlated with that of other adipokines (e.g., leptin receptor or adiponectin), which have also been identified as prognostic markers in critical illness. Conclusions. Although circulating omentin levels did not differ between ICU-patients and controls, elevated omentin levels were predictive for an impaired patients’ long term survival.

Download Full-text

Serum Perilipin 2 (PLIN2) Predicts Multiple Organ Dysfunction in Critically Ill Patients

Biomedicines ◽

10.3390/biomedicines9091210 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1210

Author(s):

Berkan Kurt ◽

Lukas Buendgens ◽

Theresa H. Wirtz ◽

Sven H. Loosen ◽

Maximilian Schulze-Hagen ◽

...

Keyword(s):

Critically Ill ◽

Organ Dysfunction ◽

Critically Ill Patients ◽

Multiple Organ ◽

Multiple Organ Dysfunction ◽

Icu Admission ◽

Metabolic Functions ◽

Metabolic Dysregulation ◽

Perilipin 2 ◽

Underlying Mechanisms

Perilipin 2 (PLIN2) is a lipid droplet protein with various metabolic functions. However, studies investigating PLIN2 in the context of inflammation, especially in systemic and acute inflammation, are lacking. Hence, we assessed the relevance of serum PLIN2 in critically ill patients. We measured serum PLIN2 serum in 259 critically ill patients (166 with sepsis) upon admission to a medical intensive care unit (ICU) compared to 12 healthy controls. A subset of 36 patients underwent computed tomography to quantify body composition. Compared to controls, serum PLIN2 concentrations were elevated in critically ill patients at ICU admission. Interestingly, PLIN2 independently indicated multiple organ dysfunction (MOD), defined as a SOFA score >9 points, at ICU admission, and was also able to independently predict MOD after 48 h. Moreover, serum PLIN2 levels were associated with severe respiratory failure potentially reflecting a moribund state. However, PLIN2 was neither a predictor of ICU mortality nor did it reflect metabolic dysregulation. Conclusively, the first study assessing serum PLIN2 in critical illness proved that it may assist in risk stratification because it is capable of independently indicating MOD at admission and predicting MOD 48 h after PLIN2 measurement. Further evaluation regarding the underlying mechanisms is warranted.

Download Full-text