Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness
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.
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ABSTRACT: The RIFLE (Risk, Injury, Failure, Loss, and End-stage kidney disease) criteria were introduced in 2004, defining the clinical stage of acute kidney injury (AKI) and outcome measures based on serum creatinine, glomerular filtration rate, and urine output. However, a growing body of evidence suggests that these markers are insufficient in drawing an accurate illustration of kidney injury. Indeed, mortality and morbidity remain high in AKI, suggesting that accuracy and speed of patient evaluation are lacking. A great deal of evidence indicates that neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive and specific early marker of various etiological classes of AKI and would be highly valuable in conjunction with existing markers of AKI for better classifying renal injury as well as dysfunction (kidney attack). Improvements in diagnosis, risk identification, stratification, prognosis, and therapeutic monitoring will benefit clinical decision-making in the individualized bundling of therapies and ongoing patient management. In particular, kidney protection and AKI prevention may become feasible if an earlier and more accurate diagnosis is made for AKI. Here, we discuss the opportunity to consider whether NGAL is ready for routine clinical use in a number of etiologies of AKI.Critical Care 12/2014; 18(6). DOI:10.1186/s13054-014-0680-0 · 5.04 Impact Factor
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ABSTRACT: IntroductionTissue inhibitor of metalloproteinase-2 (TIMP-2) is an emerging acute kidney injury (AKI) biomarker. We evaluated the performance of urinary TIMP-2 in an adult mixed ICU by comparison with other biomarkers that reflect several different pathways of AKI.Methods This study prospectively enrolled 98 adult critically ill patients who had been admitted to the adult mixed ICU. Urinary TIMP-2 and N-acetyl-ß-D-glucosaminidase (NAG), and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6), and erythropoietin (EPO) were measured on ICU admission. We evaluated these biomarkers¿ capability of detecting AKI and its severity as determined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria and of predicting in-hospital mortality. The impact of sepsis, the leading cause of AKI in ICUs, was also evaluated.ResultsWe found AKI in 42 (42.9%) patients. All biomarkers were significantly higher in AKI than in non-AKI. In total, 27 (27.6%) patients developed severe AKI. Urinary TIMP-2 was able to distinguish severe AKI from non-severe AKI with the area under the receiver operating characteristic curve (AUC-ROC) of 0.80 (95% confidence interval 0.66 to 0.90). A total of 41 one (41.8%) cases were complicated with sepsis. Although plasma NGAL and IL-6 were increased by sepsis, urinary TIMP-2 and NAG were increased not by sepsis but by the presence of severe AKI. Plasma EPO was increased only by septic AKI. In-hospital mortality was 15.3% in this cohort. Urinary TIMP-2 and NAG, and plasma NGAL were significantly higher in non-survivors than in survivors, although plasma IL-6 and EPO were not. Among the biomarkers, only urinary TIMP-2 was able to predict in-hospital mortality significantly better than serum creatinine.Conclusion Urinary TIMP-2 can detect severe AKI with performance equivalent to those of plasma NGAL and urinary NAG with an AUC-ROC value higher than 0.80. Furthermore, urinary TIMP-2 was associated with mortality. Sepsis appeared to have only a limited impact on urinary TIMP-2, in contrast to plasma NGAL.Critical care (London, England) 12/2014; 18(6):716. DOI:10.1186/s13054-014-0716-5
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ABSTRACT: Background The role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. We hypothesized that in sepsis, the performance of serum(s) and urinary(u) NGAL can be negatively impacted by severity of illness and inflammation, and that both uNGAL and sNGAL levels can be increased regardless of presence of AKI. Methods One hundred and seven patients with sepsis were included. uNGAL and sNGAL were measured at admission (T0) and 4 hours (T4) and 24 hours later (T24). Transient and intrinsic AKI were respectively defined as AKI according to RIFLE during the first 72 hours that did or did not recover to “no AKI” in the following 72 hours. Patients were classified according to tertiles of CRP and APACHE II score increase. The relationship between sNGAL and uNGAL was assessed by linear regression. Results Fifty-seven patients developed transient and 22 intrinsic AKI. Prevalence of transient and intrinsic AKI were higher in patients with versus without septic shock (OR (95% CI):3.3(1.4-8.2)). uNGAL was associated with sNGAL, and this with parallel slopes but different intercepts for AKI (Y = 0.87*X + 314.3,R2 = 0.31) and no AKI (Y = 0.87*X + 20.1,R2 = 0.38). At T4, median uNGAL and sNGAL levels were higher in septic patients with versus without shock but this is independent of AKI ((545 ng/mL vs 196 ng/ml for uNGAL and 474 ng/ml vs 287 ng/ml for sNGAL (both P = 0.003)). Both uNGAL and sNGAL levels increased with tertiles of CRP and APACHE II score increase. Conclusions Serum and uNGAL levels are influenced by severity of illness and inflammation, and this was found to be independent of the presence of AKI. There is a strong correlation between sNGAL and uNGAL levels in patients with sepsis, indicating that increased levels of uNGAL can also be due to overspill from the systemic circulation, blurring the discriminative value of NGAL as a biomarker for AKI in patients with sepsis.BMC Nephrology 02/2015; 16(1). DOI:10.1186/s12882-015-0003-y · 1.52 Impact Factor