Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, Haase M: Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery—a prospective cohort study

Department of Intensive Care, Austin Health, Melbourne, Australia.
Critical care medicine (Impact Factor: 6.31). 01/2010; 37(2):553-60. DOI: 10.1097/CCM.0b013e318195846e
Source: PubMed


To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function.
Single-center, prospective observational study.
Tertiary hospital.
One hundred adult cardiac surgical patients.
We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate <60 mL/min), the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C, which was of fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C (p = 0.007) were independent predictors of AKI and of excellent value in the prediction of the composite end point.
Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.

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    • "Tuladhar et al. [11] reported that plasma NGAL had an AuROC of 0.85 to predict AKI after adult cardiac surgery. In another study, the AuROC was 0.73 [12]. These results are similar to ours, as we report an AuROC of 0.812–0.911. "
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    ABSTRACT: Objectives: Development of acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is relatively common and associated with increased mortality. Recently, plasma neutrophil gelatinase-associated lipocalin (NGAL) was used for the prediction of AKI. We evaluated the clinical usefulness of plasma NGAL. Design and methods: One hundred twelve adult patients undergoing cardiovascular surgery with CPB were included. Blood samples were obtained at baseline, at intensive care unit (ICU) admission, and 24h after ICU admission. The development of AKI, which is defined as an increase in serum creatinine by more than 50% within 3 postoperative days, was monitored. NGAL levels were analyzed by a Biosite Triage meter (Alere Medical, USA). Diagnostic performance of NGAL was analyzed using the area under the receiver operating characteristic curve. Results: In AKI patients (n=13), plasma NGAL levels at ICU admission were significantly higher than those at baseline [177 (122-402) vs. 121 (74-158) ng/mL, median (interquartile range), p=0.028], whereas serum creatinine showed no significant change. The predictive value of NGAL at ICU admission was 0.812 [95% confidence interval (CI), 0.68 to 0.95] with a cut-off value of 168.5ng/mL (sensitivity, 61.5%; specificity, 88.9%). After the exclusion of 35 patients with preoperative decreased renal function, the predictive value was increased to 0.911 (95% CI, 0.82 to 1.00). Conclusions: This study showed that plasma NGAL may serve as a useful biomarker for the early detection of AKI in adult patients following CPB.
    Full-text · Article · Oct 2014 · Clinical Biochemistry
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    • "In addition, NGAL concentrations begin to increase in serum and urine after 2 hours in children [20] and 1 hour in adults following CPB [21], rendering it a useful biomarker for AKI after cardiac surgery. Indeed, work by Haase-Fielitz and colleagues demonstrated that plasma NGAL levels of >150 ng/ml taken on arrival in the intensive care unit (ITU) had a 76% sensitivity and 91% specificity for predicting AKI [22]. However, the overall results of studies investigating plasma NGAL as a predictor of AKI after cardiac surgery are inconsistent, with variations in patient population, procedure type and sample collection timing limiting its current uptake in clinical practice [15,23]. "
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    ABSTRACT: Background Accurate prediction, early detection and treatment of acute kidney injury (AKI) are essential for improving post-operative outcomes. This study aimed to examine the role of aortic stiffness and neutrophil gelatinase-associated lipocalin (NGAL) as predictors of AKI or need for early medical renal intervention following aortic valve replacement (AVR). Methods Aortic pulse wave velocity and plasma NGAL were measured pre-operatively in recruited patients undergoing AVR for aortic stenosis (AS). Plasma NGAL was also measured at 3 and 18–24 hours after cardiopulmonary bypass (CPB). AKI was defined using RIFLE criteria. Early medical renal intervention included diuretics or dopamine infusion exclusively for renal causes. Results Fifty-three patients aged 71 ± 9 years were included. Sixteen (30%) developed AKI (AKI-Yes) and 24 patients (45%) received early medical intervention (Intervention-Yes). There was no significant difference in the demographic, clinical or operative characteristics between the two groups for either outcome. PWV did not significantly correlate with AKI (r = 0.12, P = 0.13) or early intervention (r = 0.18, P = 0.18). At 3 h post-CPB, plasma NGAL was a much stronger predictor of both AKI and the need for early medical intervention than conventional markers such as creatinine (AKI: AUC 83%, 95% CI 0.70–0.95 vs. AUC 65%, 95% CI 0.47- 0.82; Medical intervention: AUC 84%, 95% CI 0.72–0.96 vs. AUC 56%, 95% CI 0.38–0.73). Post-CPB (3 hr) plasma NGAL was also significantly associated with AKI (r = 0.68, P < 0.001) at levels above 150 ng/ml; and significantly associated with early intervention (r = 0.64, P < 0.001) above 136 ng/ml. Simple linear regression showed no relationship between PWV and NGAL levels. Conclusion Aortic PWV does not correlate significantly with post-operative AKI or plasma NGAL levels in surgical AS patients. Post-operative NGAL is however an early and powerful predictive biomarker of both post-operative AKI and the need for early medical renal intervention and should consequently be considered in prediction models for AKI after cardiac surgery.
    Full-text · Article · May 2014 · Journal of Cardiothoracic Surgery
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    • "Cystatin performs better than creatinine in early detection of AKI in the emergency room [7], intensive care unit (ICU) [8] [9], and following pediatric cardiac surgery [10]. Cystatin associates with duration of AKI [11], need for renal replacement therapy [8] [12], and short and long term mortality in AKI [12] [13]. Patients who experience increases in both cystatin C and creatinine experience worse outcomes than those with an increase in either marker alone [14] [15]. "
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    ABSTRACT: Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, P = 0.02 and 0.03 , respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes.
    Full-text · Article · Mar 2014 · International Journal of Nephrology
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