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

Division of Critical Care Medicine, University of Alberta Hospital, University of Alberta, 3C1.16 Walter C Mackenzie Centre, 8440-122 Street, Edmonton, AB T6G2B7, Canada.
Intensive Care Medicine (Impact Factor: 7.21). 12/2009; 36(3):452-61. DOI: 10.1007/s00134-009-1724-9
Source: PubMed

ABSTRACT 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.
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.

  • Source
    • "and probably the most promising of them because of the results obtained in different scenarios and clinical conditions [26] [27] [28] [29] [30]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to determine if complement pathway is activated in AKI; for this purpose, we measured, through ELISA sandwich, the terminal lytic fraction of the complement system, called membrane attack complex (C5b-C9), in AKI patients compared with patients with similar clinical conditions but normal renal function. Our data showed that complement system is activated in AKI. Plasmatic MAC concentrations were significantly higher in AKI patients than in those with normal renal function; this difference is maintained independently of the AKI etiology and is proportional to the severity of AKI, measured by ADQI classification. In addition, we found that plasmatic MAC concentrations were significantly higher in patients who did not recover renal function at time of hospitalization discharge, in patients who died during the acute process, and in patients who need renal replacement therapy during hospitalization, but in this last group, the differences did not reach statistical significance. In conclusion, plasmatic MAC concentration seems valuable as a marker of AKI severity.
    BioMed Research International 05/2014; 2014:361065. DOI:10.1155/2014/361065 · 2.71 Impact Factor
  • Source
    • "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]. However, it remains to be elucidated whether continuous venovenous hemofiltration (CVVH) in the treatment of AKI affects plasma NGAL levels and thus the biomarker value, either by clearance, adsorption, or production of NGAL in the filter. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "In contrast to our previous study, which included AKI at ICU entry [11], the primary endpoint for the current study was AKI development within 48 h following ICU admission. Indeed, AKI prediction is more useful than confirming established AKI; however, many previous studies grouped together developing and established AKI, thereby potentially leading to predictive value overestimation [1-6,8-10,12,13,21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The predictive value of acute kidney injury (AKI) urinary biomarkers may depend on the time interval following tubular injury, thereby explaining in part the heterogeneous performance of these markers that has been reported in the literature. We studied the influence of timing on the predictive values of tubular proteins, measured before the rise of serum creatinine (SCr) in critically ill, non-septic patients. Seven hundred adult critically ill patients were prospectively included for urine measurements at four time-points prior to the rise in serum creatinine (T = 0, -16, -20 and -24 h). Patients with sepsis and or AKI at ICU entry were excluded. The urinary excretion of the proteins, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), which are up-regulated in the distal and proximal tubules, respectively, were measured as well as the constitutive cytoplasmatic enzymes, pi- and alpha-glutathione-S-transferase (GST), which are released by the distal and proximal tubules, respectively. Five hundred and forty-three subjects were eligible for further analyses; however, 49 developed AKI in the first 48 h. Both NGAL (P = 0.001 at T = -24 vs. non-AKI patients) and KIM-1 (P < 0.0001 at T = 0 vs. non-AKI patients) concentrations gradually increased until AKI diagnosis, whereas pi- and alpha-GST peaked at T = -24 before AKI (P = 0.006 and P = 0.002, respectively vs. non-AKI patients) and showed a rapid decline afterwards. The predictive values at T = -24 prior to AKI were modest for pi- and alpha-GST, whereas NGAL sufficiently predicted AKI at T = -24 and its predictive power improved as the time interval to AKI presentation decreased (area under the receiver operating characteristic curve; AUC = 0.79, P < 0.0001). KIM-1 was a good discriminator at T = 0 only (AUC = 0.73, P < 0.0001). NGAL, KIM-1, pi- and alpha-GST displayed unique and mutually incomparable time dependent characteristics during the development of non-sepsis related AKI. Therefore, the time-relationship between the biomarker measurements and the injurious event influences the individual test results.
    BMC Nephrology 12/2013; 14(1):273. DOI:10.1186/1471-2369-14-273 · 1.52 Impact Factor
Show more