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      The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

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          Abstract

          Introduction

          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.

          Methods

          Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was 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 with enzyme-linked immunosorbent assay (ELISA).

          Results

          Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. 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).

          Conclusions

          The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied.

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          Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness.

          Michael B. Bennett, Sean Bagshaw, Hiroshi Morimatsu … (2010)
          Sepsis is the most common trigger for acute kidney injury (AKI) in critically ill patients. We sought to determine whether there are unique patterns to plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in septic compared with non-septic AKI. Prospective observational study. Two adult ICUs in Melbourne, Australia. Critically ill patients with septic and non-septic AKI. None. Blood and urine specimens collected at enrollment, 12, 24 and 48 h to measure plasma and urine NGAL. Eighty-three patients were enrolled (septic n = 43). Septic AKI patients had more co-morbid disease (p = 0.005), emergency surgical admissions (p < 0.001), higher illness severity (p = 0.008), more organ dysfunction (p = 0.008) and higher white blood cell counts (p = 0.01). There were no differences at enrollment between groups in AKI severity. Septic AKI was associated with significantly higher plasma (293 vs. 166 ng/ml) and urine (204 vs. 39 ng/mg creatinine) NGAL at enrollment compared with non-septic AKI (p < 0.001). Urine NGAL remained higher in septic compared with non-septic AKI at 12 h (p < 0.001) and 24 h (p < 0.001). Plasma NGAL showed fair discrimination for AKI progression (area under receiver-operator characteristic curve 0.71) and renal replacement therapy (AuROC 0.78). Although urine NGAL performed less well (AuROC 0.70, 0.70), peak urine NGAL predicted AKI progression better in non-septic AKI (AuROC 0.82). Septic AKI patients have higher detectable plasma and urine NGAL compared with non-septic AKI patients. These differences in NGAL values in septic AKI may have diagnostic and clinical relevance as well as pathogenetic implications.
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            Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury.

            Johan Mårtensson, Max Bell, Anders Oldner … (2010)
            To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock. Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine alpha1-microglobulin. Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock. pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.
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              Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population

              Dinna Cruz, Massimo De Cal, Francesco Garzotto … (2009)
              Purpose Neutrophil gelatinase-associated lipocalin (NGAL) is a useful marker for acute kidney injury (AKI), particularly when the timing of renal insult is known. However, its performance in an adult critical care setting has not been well described. We performed this study to estimate the diagnostic accuracy of plasma NGAL for early detection of AKI and need for renal replacement therapy (RRT) in an adult intensive care unit (ICU). Methods We enrolled 307 consecutive adult patients admitted to a general medical-surgical ICU; 301 were included in the final analysis. Serial blood samples were analyzed for plasma NGAL using a standardized clinical platform. The primary outcome was AKI, defined as an increase in creatinine of at least 50% from baseline or a reduction in urine output to 6 h. Results Of 301 patients, 133 (44%) had AKI during their ICU stay. Plasma NGAL was a good diagnostic marker for AKI development within the next 48 h (area under ROC 0.78, 95% CI 0.65–0.90), and for RRT use (area under ROC 0.82, 95% CI 0.70–0.95). Peak plasma NGAL concentrations increased with worsening AKI severity (R = 0.554, P < 0.001). Conclusions Plasma NGAL is a useful early marker for AKI in a heterogeneous adult ICU population, in which the timing of renal insult is largely unknown. It allows the diagnosis of AKI up to 48 h prior to a clinical diagnosis based on AKI consensus definitions. Additionally, it predicts need for RRT and correlates with AKI severity. Early identification of high risk patients may allow potentially beneficial therapies to be initiated early in the disease process before irreversible injury occurs. Electronic supplementary material The online version of this article (doi:10.1007/s00134-009-1711-1) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Louise Schilder
                S Azam Nurmohamed
                Pieter M ter Wee
                Nanne J Paauw
                Armand RJ Girbes
                Albertus Beishuizen
                Robert HJ Beelen
                AB Johan Groeneveld
                Journal
                Journal ID (nlm-ta): Crit Care
                Journal ID (iso-abbrev): Crit Care
                Title: Critical Care
                Publisher: BioMed Central
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Print): 2014
                Publication date (Electronic): 22 April 2014
                Volume: 18
                Issue: 2
                Page: R78
                Affiliations
                [1 ]Department of Nephrology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
                [2 ]Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
                [3 ]Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands
                [4 ]Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands
                Article
                Publisher ID: cc13838
                DOI: 10.1186/cc13838
                PMC ID: 4056788
                PubMed ID: 24755339
                SO-VID: 2eb0f52f-46ab-4a62-b9e4-62716a6e39e0
                Copyright © Copyright © 2014 Schilder et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 21 January 2014
                Date accepted : 2 April 2014
                Categories
                Subject: Research

                ScienceOpen disciplines: Emergency medicine & Trauma
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma

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