Clinical paperPlasma neutrophil gelatinase-associated lipocalin as an early predicting biomarker of acute kidney injury and clinical outcomes after recovery of spontaneous circulation in out-of-hospital cardiac arrest patients☆
Introduction
Out-of-hospital cardiac arrest (OHCA) is a major health problem because it is associated with high rates of mortality and disability. Despite considerable efforts to improve the treatment of cardiac arrest, most reported survival outcome figures are poor,1 and 29.4% die from multiple organ failure after intensive care unit (ICU) admission.2 Cardiac arrest causes general ischaemia/hypoxia, which can affect the kidneys. Renal dysfunction is common after OHCA and causes adverse effects and poor outcomes.3 The serum creatinine concentration is an indicator of the glomerular filtration rate (GFR) and reduced kidney function.4 Therefore, the serum creatinine concentration is used in many criteria to assess acute kidney injury (AKI), such as the Risk, Injury, Failure, Loss, and End-stage Kidney classification, Acute Kidney Injury Network (AKIN), and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.5, 6 Serum creatinine concentration can vary widely with age, sex, muscle mass, muscle metabolism, medications and hydration status. However, the increase in serum creatinine concentration in response to kidney injury can be delayed by several days and may not occur until kidney function is already impaired.7, 8
Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein that is stored in granules within mature neutrophils and is produced in the kidney after ischaemic or nephrotoxic injury.9, 10, 11, 12 NGAL is an early and specific marker of tubular damage and may predict a poor outcome of AKI.13 Previous results suggested that plasma and urine NGAL concentrations represent predictive biomarkers of AKI in the ICU setting and may predict this complication about 2 days before the increase in serum creatinine concentration.14 NGAL is emerging as a centre-stage player in the AKI field as a predictive biomarker in coronary artery disease (CAD), acute myocardial infarction (AMI), cardiac surgery, sepsis and major burn patients.15, 16, 17, 18, 19, 20 For patients with cardiac arrest, AKI is not typically a direct cause of death from multiple organ failure. However, the presence of AKI might be related to high mortality rates and poor outcomes in patients after cardiac arrest. For these patients, kidney damage may be influenced by primarily global ischaemia resulting from the lack of systemic flow during the arrest phase, and reperfusion injury and the systemic inflammatory reaction after recovery of spontaneous circulation.21, 22 We speculated that plasma NGAL may be a strong biomarker for early prediction of AKI in patients after cardiac arrest, and associated with patient survival and neurological outcomes. The first aim of the study was to determine whether plasma NGAL levels at admission are a reliable predictor of AKI in patients with OHCA admitted to the ICU after recovery of spontaneous circulation (ROSC). We also sought to evaluate the relationship between plasma NGAL and 30-day survival and neurological outcomes in patients after cardiac arrest.
Section snippets
Study design or patient selection
This prospective, observational study was performed in the emergency department and ICU of our medical centre (Anyang, Republic of Korea) between January 2013 and March 2015. The protocol of this study was approved by the Institutional Review Board of our hospital, and written informed consent was obtained from the closest relatives. The emergency centre is in a tertiary care hospital, and the annual emergency department (ED) volume was about 79,000 in 2014.
All consecutive patients aged 18
Baseline data
During the study period, a total of 200 OHCA patients were admitted to the ED, and 81 patients achieved ROSC. Twenty-seven patients were excluded: three because of pre-injury chronic renal failure, three because of traumatic arrest, and twelve who died before ICU admission. Informed consent was not obtained from next of kin for nine patients (Fig. 1). Lastly, 54 patients were included. All patients were admitted in the ICU, and all blood samples were drawn within 4 h after ROSC (median time was
Discussion
Our observational clinical study found that plasma NGAL concentration at admission was efficient in independently predicting AKI in patients exhibiting OHCA at ICU admission. Plasma NGAL concentration at admission had good power to predict 30-day survival (0.810 of AUC) and NGAL concentration >189 ng ml−1 was associated with a 7-fold higher incidence of AKI in our adjusted models. In addition, we newly determined the strong relationship between the lower plasma NGAL concentration and greater
Conclusion
Plasma NGAL concentration at ICU admission was a strong predictor for AKI in patients with OHCA at ICU admission. In addition, low plasma NGAL concentrations were associated with a good chance of 30-day survival and good neurological outcome in these patients.
Conflict of interest statement
None of the authors declare any conflict of interests.
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2016.01.005.
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Sang O. Park and Ji Yun Ahn are the first authors who contributed equally to the study.