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Does Whole-Blood Neutrophil Gelatinase-Associated Lipocalin Stratify Acute Kidney Injury in Critically Ill Patients?

ABSTRACT: Purpose:To analyse the capacity of whole-blood NGAL (wbNGAL) to stratify AKI in critically ill patients with and without sepsis. Methods:Whole-blood NGAL was measured with a point-of-care device at admission and 48 hours later in patients admitted to a general ICU. Patients were classified by the AKIN and KDIGO classifications at admission and 24 and 48 hours. We performed an ROC curve analysis. wbNGAL values at admission were compared in patients with sepsis and septic shock. Results:The study included 100 consecutively admitted patients (40 female) with mean age 59.1 ± 17.8 years. Thirty-three patients presented AKI at admission, and 10 more developed it in the next 48?h. Eighteen patients had AKI stage 3, 14 of them at admission. Nine patients required renal replacement therapy. According to KDIGO at admission, wbNGAL values were 78??g/L (60-187) in stage 0 (n = 67), 263??g/L (89-314) in stage 1 (n = 8), 484??g/L (333-708) in stage 2 (n = 11), and 623??g/L (231-911) in stage 3 (n = 14), p = 0.0001 for trend. Ten patients did not complete 48 hours of study: 6 of 10 were discharged (initial wbNGAL 130??g/L (60-514)) and 4 died (773??g/L (311-1010)). The AUROC curve of wbNGAL to predict AKI was 0.838 (95% confidence interval 0.76-0.92, p = 0.0001), with optimal cut-off value of 178??g/L (sensitivity 76.7%, specificity 78.9%, p < 0.0001). At admission, twenty-nine patients had sepsis, of whom 20 were in septic shock. wbNGAL concentrations were 81??g/L (60-187) in patients without sepsis, 481 (247-687) in those with sepsis, and 623.5??g/L (361-798) in the subgroup of septic shock (p < 0.0001). Conclusions:Whole-blood NGAL concentration at ICU admission was a good stratifier of AKI in critically ill patients. However, wbNGAL concentrations were higher in septic patients irrespective of AKI occurrence.

SUBMITTER: Cuartero M

PROVIDER: S-EPMC6525902 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Does Whole-Blood Neutrophil Gelatinase-Associated Lipocalin Stratify Acute Kidney Injury in Critically Ill Patients?

Cuartero M M Betbesé A J AJ Núñez K K Baldirà J J Ordonez-Llanos J J

Disease markers 20190502

<h4>Purpose</h4>To analyse the capacity of whole-blood NGAL (wbNGAL) to stratify AKI in critically ill patients with and without sepsis.<h4>Methods</h4>Whole-blood NGAL was measured with a point-of-care device at admission and 48 hours later in patients admitted to a general ICU. Patients were classified by the AKIN and KDIGO classifications at admission and 24 and 48 hours. We performed an ROC curve analysis. wbNGAL values at admission were compared in patients with sepsis and septic shock.<h4> ...[more]

PMID: 31191757

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Project description:IntroductionNeutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a useful early diagnostic biomarker of acute kidney injury (AKI) where the timing of the insult is certain. However, NGAL is not well validated in adult critical care practice because of indeterminate timing of injury. Therefore, we sought to establish the predictive ability of both urine and plasma NGAL to detect AKI in ICU patients.MethodThis prospective observational study was performed in a busy large district general hospital mixed surgical-medical ICU in Reading, UK. Consecutive adult admissions to the ICU, with absence of chronic kidney disease, renal transplant or AKI as defined by RIFLE criteria were included. Blood and urine specimens were collected at admission and every 24 hours until 72 hours and tested for NGAL. The purpose of the study was to assess whether urinary NGAL (uNGAL) or plasma NGAL (pNGAL) can predict the occurrence of AKI at an earlier point of time than the conventional markers, that is creatinine and urine output as is used in RIFLE criteria.ResultsOver a 12-month period, 194 patients were enrolled. In total, 59 (30.4%) patients developed AKI. The admission pNGAL and uNGAL were significantly higher in the patients who developed AKI compared to the non-AKI patients (436 ng/mL (240, 797) versus 168 ng/mL (121.3, 274.3) P <0.001 and 342 ng/mL (61.5, 1,280) versus 34.5 ng/mL (11.5, 107.75) P <0.001 respectively). Hospital mortality was higher in the AKI group (17% versus 4%). Plasma NGAL performed fairly on admission (AUROC 0.77) and thereafter performance improved at 24 and 48 hours (AUROC 0.88 and 0.87) following ICU admission. Urine NGAL had a fair predictive value on admission (AUROC 0.79) and at 24 hours (AUROC 0.78) and was good at 48 hours (AUROC 0.82).ConclusionsIn critically ill patients without pre-existing kidney disease, both pNGAL and uNGAL measured at admission can predict AKI (defined by RIFLE criteria) occurrence up to 72 hours post-ICU admission and their performance (AUROC) was fair. The accuracy of NGAL appeared to improve slightly as patients progressed through their ICU stay. Serial measurements of NGAL (both pNGAL and uNGAL) may be of added value in an ICU setting to predict the occurrence of AKI.

Project description:We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls.Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater.Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate.Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

Project description:BackgroundContinuous renal replacement therapy (CCRT) is a frequently used modality for the support of intensive care patients with acute kidney injury (AKI). Nevertheless, there are no objective criteria for the discontinuation of CRRT. The purpose of this study was to investigate whether urine neutrophil gelatinase-associated lipocalin (uNGAL) alone or in combination with urine output could be used as a diagnostic test for renal function recovery in ICU patients on CRRT.MethodsThis was a single-centre prospective observational study including patients with acute kidney failure needing CRRT. Sixty-nine patients were enrolled, and 54 completed the study. Of the 54 patients, 22 recovered renal function (REC), defined as dialysis independency at 72 h from discontinuation, while 32 patients did not (NREC). Urine NGAL was measured at 0, 6, 12, and 24 h after CRRT discontinuation. The cumulated urine output was measured for 24 h prior to discontinuation and at 6, 12, and 24 h after discontinuation. Missing uNGAL values were calculated by interpolation. The Youden's index was used to calculate cut-off values in order to define uNGAL and urine output single variable and 2-variable diagnostic tests with the optimum prediction of successful CRRT discontinuation.ResultsBaseline characteristics at CRRT initiation were similar between groups. Compared to the NREC group, the REC group had significantly higher urine output (p < 0.0001) and lower uNGAL (p < 0.001) at all time points, except for uNGAL at 24 h (p < 0.24). The best uNGAL predictor for successful CRRT discontinuation was uNGAL at 6 h after discontinuation (predictive value 80%). The best single predictor was cumulated urine output 24 h before discontinuation (predictive value 85%). The combinations of uNGAL at 6 h (cut-off 1650 μg/L) with cumulated urine output 24 h prior to discontinuation (cut-off 210 ml) proved to be the superior tests (using either "or" or "and"), with predictive values of 93% (successful CRRT discontinuation) and 92% (dialysis dependency).ConclusionsWith a predictive value of 93%, the combination of uNGAL at 6 h after and the cumulated urine output 24 h prior to CRRT cessation proved to be the best diagnostic test for successful CRRT discontinuation in ICU patients.Clinical trial registrationN/A.

Project description:BackgroundFew studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin.MethodsParticipants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher).ResultsOf 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65).ConclusionsUrine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Project description:BackgroundAcute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated.MethodsThis was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death.Main outcomesThirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h.ConclusionsMajority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation.Trial registrationThis was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].

Project description:Background and objectivesElevated levels of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are associated with negative outcomes in CKD. Our study aimed to explore the prognostic accuracy of blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for progression to ESRD, major adverse cardiovascular events, and death in a large cohort of adult patients with all-cause nondialysis-dependent CKD stages 3-5. We considered whether these factors improve prediction in relation to traditional biomarkers and clinical parameters.Design, setting, participants, & measurementsKidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were measured on baseline plasma samples from 1982 patients who were recruited to the Chronic Renal Insufficiency Standards Implementation Study between the start of June of 2002 and the start of June of 2013. Associations with study end points were assessed using Cox regression models, receiver operator characteristic curve analyses, and reclassification statistics.ResultsOver a median follow-up of 29.5 months (interquartile range, 14.9-53.5), 21.6% of patients progressed to ESRD, 27% died, and 6.6% suffered a major adverse cardiovascular event. Higher blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were independently associated with a greater risk for ESRD (hazard ratio, 1.25; 95% confidence interval, 1.10 to 1.43; P<0.001 and hazard ratio, 1.35; 95% confidence interval, 1.14 to 1.59; P?0.001, respectively, per 1 SD higher biomarker concentration). There was no association with risk for cardiovascular events or death. The addition of biomarkers to our baseline risk model of traditional clinical characteristics and laboratory parameters did not significantly improve model discrimination or risk reclassification.ConclusionsIn patients with moderate to severe CKD, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin blood levels are independent risk factors for progression to ESRD. Additional studies are needed to establish the utility and cost-effectiveness of these novel biomarkers in the clinical setting.

Dataset Information

Does Whole-Blood Neutrophil Gelatinase-Associated Lipocalin Stratify Acute Kidney Injury in Critically Ill Patients?

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Does Whole-Blood Neutrophil Gelatinase-Associated Lipocalin Stratify Acute Kidney Injury in Critically Ill Patients?

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