Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and eGFR Indicate Acute Kidney Injury and Predict Prognosis of Patients With Acute Pulmonary Embolism

Study Questions:

Is acute kidney injury (AKI), as measured by renal biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and cystatin C, predictive of prognosis in patients with acute pulmonary embolism (PE)?


The authors reported data on consecutive patients with symptomatic acute PE between 2008 and 2009, at the Medical University of Warsaw. Diagnosis was confirmed through contrast-enhanced spiral computed tomography, and patients who were recruited within 14 days of symptom onset. Blood samples obtained at admission were assayed for N-GAL and cystatin C, as well as creatinine, to calculate estimated glomerular filtration rate (eGFR) using the MDRD formula. Standard statistical tests were used for comparison between groups. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated for biomarker cutoff values identified by receiver operating characteristic (ROC) curves. Association of biomarker levels with mortality was evaluated using Cox proportional hazard models.


Of the 142 consecutive patients identified (age 64 ± 18 years; 63% female), 14 (10%) died by the 30th day. Renal function in the form of eGFR was higher in survivors than nonsurvivors (66 vs. 46 ml/min, respectively; p = 0.02). N-GAL was higher in subjects who died (88.8 vs. 53.0 ng/ml, p < 0.01). N-GAL as a predictor of all-cause mortality revealed an area under ROC curve of 0.715. Cystatin C, on the other hand, was not elevated among subjects who died, and did not have an increased area under curve on ROC analysis. For a value of N-GAL >75 ng/ml, the sensitivity, specificity, PPV, and NPV for all-cause mortality were 64%, 73%, 21%, and 95%, respectively. A value of cystatin C >1900 ng/ml had great specificity, but not sensitivity for mortality, with associated sensitivity, specificity, PPV, and NPV of 36%, 91%, 30%, and 93%, respectively. N-GAL >75 ng/ml and cystatin C >1900 ng/ml were associated with an increased risk of death (hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.48-13.20; p < 0.01, and HR, 4.7; 95% CI, 1.56-13.90; p = 0.01), respectively.


The authors concluded that kidney injury assessed by N-GAL and cystatin C occurs in 30% of PE cases, and may contribute to the impairment of renal function present in one-half of such cases. The authors further opined that N-GAL or cystatin C elevation, and a low eGFR, are associated with poor 30-day prognosis in PE.


Much of the epidemiologic literature on acute PE, at least in the United States, has focused on risk tools and risk factors for predicting the presence of PE. The European Society of Cardiology guidelines have focused on stratifying mortality risk in acute PE, with an eye toward possible use of more aggressive therapy (i.e., thrombolytics) in patients without hypotension or shock, but at increased risk of death. Those guidelines suggest using right ventricular dysfunction on echocardiography, and elevated biomarkers in the form of troponin or B-type natriuretic peptide, to identify acute PE patients who may benefit from thrombolytic therapy. The current study suggests that biomarkers of AKI may likewise identify acute PE patients at increased risk of death. Although these data may help guide future study, it is not clear how this prognostic information may help the clinician, and even less clear that any change in therapy, such as the use of thrombolytics, can be guided by these markers. Clearly, further study is needed.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Vascular Medicine, Lipid Metabolism, Heart Failure and Cardiac Biomarkers

Keywords: Thrombolytic Therapy, Shock, Pulmonary Embolism, Acute Kidney Injury, Hypotension, Fibrinolytic Agents, Ventricular Dysfunction, Right, Survivors, Lipocalins, Prognosis, Cardiology, Glomerular Filtration Rate, Confidence Intervals, United States, Cystatin C, Natriuretic Peptide, Brain, Troponin

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