Neutrophil Gelatinase-associated Lipocalin at ICU Admission Predicts for Acute Kidney Injury in Adult Patients

Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 10/2010; 183(7):907-14. DOI: 10.1164/rccm.200908-1214OC
Source: PubMed

ABSTRACT Measured at intensive care unit admission (ICU), the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) for severe acute kidney injury (AKI) is unclear.
To assess the ability of plasma and urine NGAL to predict severe AKI in adult critically ill patients.
Prospective-cohort study consisting of 632 consecutive patients.
Samples were analyzed by Triage immunoassay for NGAL expression. The primary outcome measure was occurrence of AKI based on Risk-Injury-Failure (RIFLE) classification during the first week of ICU stay. A total of 171 (27%) patients developed AKI. Of these 67, 48, and 56 were classified as RIFLE R, I, and F, respectively. Plasma and urine NGAL values at ICU admission were significantly related to AKI severity. The areas under the receiver operating characteristic curves for plasma and urine NGAL were for RIFLE R (0.77 ± 0.05 and 0.80 ± 0.04, respectively), RIFLE I (0.80 ± 0.06 and 0.85 ± 0.04, respectively), and RIFLE F (0.86 ± 0.06 and 0.88 ± 0.04, respectively) and comparable with those of admission estimated glomerular filtration rate (eGFR) (0.84 ± 0.04, 0.87 ± 0.04, and 0.92 ± 0.04, respectively). Plasma and urine NGAL significantly contributed to the accuracy of the "most efficient clinical model" with the best four variables including eGFR, improving the area under the curve for RIFLE F prediction to 0.96 ± 0.02 and 0.95 ± 0.01. Serial NGAL measurements did not provide additional information for the prediction of RIFLE F.
NGAL measured at ICU admission predicts the development of severe AKI similarly to serum creatinine-derived eGFR. However, NGAL adds significant accuracy to this prediction in combination with eGFR alone or with other clinical parameters and has an interesting predictive value in patients with normal serum creatinine.

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Available from: Hilde De Geus, Sep 28, 2015
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    • "Approximately 30% of critically ill patients admitted to an intensive care unit (ICU) develop acute kidney injury (AKI) [1]. Biomarker neutrophil gelatinase-associated lipocalin (NGAL) is associated with the development of AKI, the need for dialysis, and mortality [1-4]. "
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    ABSTRACT: Background: Previous pharmacokinetic trials suggested that 40 mg subcutaneous enoxaparin once daily provided inadequate thromboprophylaxis for intensive care unit patients. Critically ill patients with acute kidney injury are at increased risk of venous thromboembolism and yet are often excluded from these trials. We hypothesized that for critically ill patients with acute kidney injury receiving continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously once daily would improve thromboprophylaxis without increasing the risk of bleeding. In addition, we seek to utilize urine output prior to discontinuing dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free intervals, as markers of renal recovery. Methods/design: In a multicenter, double-blind randomized controlled trial in progress at three intensive care units across Denmark, we randomly assign eligible critically ill adults with acute kidney injury into a treatment (1 mg/kg enoxaparin subcutaneously once daily) or control arm (40 mg enoxaparin subcutaneously once daily) upon commencement of continuous renal replacement therapy.We calculated that with 133 patients in each group, the study would have 80% power to show a 40% reduction in the relative risk of venous thromboembolism with 1 mg/kg enoxaparin, at a two-sided alpha level of 0.05. An interim analysis will be conducted after the first 67 patients have been included in each group.Enrolment began in March 2013, and will continue for two years. The primary outcome is the occurrence of venous thromboembolism. Secondary outcomes include anti-factor Xa activity, bleeding, heparin-induced thrombocytopenia, filter lifespan, length of stay, ventilator free days, and mortality. We will also monitor neutrophil gelatinase-associated lipocalin and urine volume to determine whether they can be used as prognostic factors for renal recovery. Discussion: Critically ill unit patients with acute kidney injury present a particular challenge in the provision of thromboprophylaxis. This study hopes to add to the growing evidence that the existing recommendation of 40 mg enoxaparin is inadequate and that 1 mg/kg is both safe and effective for thromboprophylaxis.In addition, the study seeks to identify predictors of renal recovery allowing for the proper utilization of resources. Trial registration: EU Clinical Trials Register: EudraCT number: 2012-004368-23, 25 September 2012.
    Trials 06/2014; 15(1):226. DOI:10.1186/1745-6215-15-226 · 1.73 Impact Factor
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    • "Current possible assays include (1) AKI biomarkers in urine and plasma. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) is currently the best validated biomarker of AKI [44]. Alternative biomarkers of AKI (such as Kidney Injury Molecule-1 or cell cycle arrest biomarkers [45]) may be better characterised and validated by the end of the trial. "
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    ABSTRACT: Background Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients. Methods/Design This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μ or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom. Discussion This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action. Trial registration Current controlled trials ISRCTN12776039 (19 September 2013)
    Trials 06/2014; 15(1):199. DOI:10.1186/1745-6215-15-199 · 1.73 Impact Factor
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    • "It is also rapidly induced in distal tubular segments of injured nephrons with stress [3]. Therefore, urinary and plasma levels are helpful in early prediction of AKI [4-7], in prediction of severity of AKI [6-9] and AKI-related outcomes, such as the need for renal-replacement therapy (RRT), as well as mortality [5-7,9-12]. Also, levels of NGAL are associated with disease severity, and its levels are more profoundly elevated during sepsis [5,7,11,13-15]. "
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    ABSTRACT: Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI) and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI. Immediately before initiation of CVVH, pre-filter blood was drawn. After 10, 60, 180 and 720 minutes of CVVH, samples were collected from pre- and post-filter (in- and out-let) blood and ultrafiltrate. CVVH with the following anticoagulation regimens were studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8) or trisodium citrate (n = 21). NGAL levels were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of NGAL at inlet and outlet were similar and concentrations did not change over time in any of the anticoagulation groups, thus there was no net removal or production of NGAL. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001). The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, since clearance by the filter was low. Furthermore, there is no evidence for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied.
    Critical care (London, England) 04/2014; 18(2):R78. DOI:10.1186/cc13838 · 4.48 Impact Factor
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