Neutrophil Gelatinase-Associated Lipocalin (NGAL): Validation of commercially available ELISA

Abstract

Background. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been described as an excellent marker of acute kidney injury (AKI) using the enzyme-linked immunosorbent assay (ELISA) from BioPorto Diagnostics, DK. Validation of the ELISA kit and investigation of stability of the NGAL protein is a prerequisite before introducing NGAL as a marker for AKI in clinical research. Methods. Plasma and urine samples from a healthy adult and from 16 children undergoing surgery for congenital heart disease were used to validate the 036 NGAL ELISA kit from BioPorto Diagnostics and study stability of the NGAL protein. Results. Median intra-assay variation in plasma and urine from the healthy adult was <5% and median inter-assay variation was <10%. For children undergoing surgery for congenital heart disease intra-assay variation was <10%. ELISA kit batch-to-batch variation for plasma was 14.6%. We observed excellent results on analysis of linearity and spike-recovery and found no clinically important variation of NGAL measurements throughout the ELISA plate. Haemolysis significantly interfered with measurement of NGAL, whereas repeated thawing or 48 h of 4–5°C-storage before centrifugation and storage at ?80°C did not influence NGAL measurements (ANOVA; n.s.). The NGAL protein is stable in plasma for at least 11 months at ?80°C. Conclusion. 036 NGAL ELISA kit from BioPorto Diagnostics can be used with acceptable precision for plasma and urine. However, the presence of haemolysis in blood samples or the use of different batches of ELISA kits may seriously decrease the accuracy of measurements.     

Plasma neutrophil gelatinase-associated lipocalin as a predictive biomarker for the detection of acute kidney injury in adult poisoning

Context: Acute kidney injury (AKI) is a serious complication in intoxicated patients. Recently, a new biomarker - neutrophil gelatinase-associated lipocalin (NGAL) - was used to predict AKI in patients who were critically ill or had sepsis. Objective: To evaluate the utility of plasma NGAL as an early predictor of AKI in adults with acute poisoning. Materials and methods: This retrospective, observational, cohort study was conducted between December 2013 and November 2014. A total of 157 consecutive adult patients who presented to the emergency department (Level 1 regional center) of Kyungpook National University Hospital, a tertiary teaching hospital in Daegu, Korea, within 24 h of poisoning were included. Initial plasma NGAL levels and laboratory parameters were concurrently measured upon hospital arrival. AKI was defined according to Acute Kidney Injury Network criteria. Development of AKI was predicted using plasma NGAL levels and by analyzing the area under the receiver operating characteristic curve (AUC). Results: The overall rate of AKI was 14.6% (n?=?23). Plasma NGAL levels in the AKI group were higher than those in the non-AKI group (median, 310 vs. 86 ng/mL; p?<0.001). Additionally, baseline NGAL levels allowed for better prediction of AKI than initial creatinine levels. The AUC of plasma NGAL was 0.895 (95% confidence interval [CI]: 0.832–0.941), with a cut-off value of 227 ng/mL (sensitivity, 76.2%; specificity, 95.8%). Plasma NGAL had a higher predictive capacity for AKI than serum creatinine (AUC 0.741, 95% CI: 0.662–0.810), base deficit (AUC 0.795, 95% CI: 0.701–0.870), lactate (AUC 0.781, 95% CI: 0.690–0.856), and anion gap (AUC 0.636, 95% CI: 0.535–0.730). Conclusion: Plasma NGAL may serve as a good predictor of AKI in cases of adult poisoning.     

Significant elevation and correlation of plasma neutrophil gelatinase associated lipocalin and its complex with matrix metalloproteinase-9 in patients with pelvic inflammatory disease

BackgroundsTo detect the expression of plasma neutrophil gelatinase associated lipocalin (NGAL) and its complex with matrix metalloproteinase-9 (MMP-9) in patients with pelvic inflammatory disease (PID).MethodsEnzyme-linked immunosorbent assay was used to measure the levels of plasma NGAL and NGAL/MMP-9 complex.ResultsThe levels of plasma NGAL or NGAL/MMP-9 complex were increased in patients with PID compared with those in normal controls and decreased significantly after treatment. Pre-treatment plasma level of NGAL was significantly correlated with WBC and neutrophil counts. In patients with PID, plasma level of NGAL/MMP-9 complex was correlated with plasma level of NGAL or MMP-9 significantly. In predicting PID, the sensitivities of NGAL and NGAL/MMP-9 complex were 76.6% and 78.1%; the negative predictive values, 72.7% and 74.5%.ConclusionsPlasma NGAL and NGAL/MMP-9 complex may act as diagnostic adjuvant biomarkers for PID. In patients with PID, about 80% have plasma levels of NGAL or NGAL/MMP-9 complex level > 10.04 ng/ml or 2.33 ng/ml, respectively.     

Interleukin-6 serum level assessment using a new qualitative point-of-care test in sepsis: A comparison with ELISA measurements

ObjectivesInterleukin-6 (IL-6) is involved in inflammatory diseases, provides prognostical information, and allows the early identification and monitoring of septic patients. We investigated whether IL-6 can be assessed using a new densitometric point-of-care (POC) bedside assay.Design and methods392 samples were prospectively collected from 57 intensive care unit patients (38 male, age: 45.2 ± 16.9years, APACHE II score: 25.4 ± 4.8). Blinded IL-6 measurements were performed using conventional semiautomatic enzyme-linked immunosorbent assays (ELISA) and the POC test.ResultsMean IL-6 levels were 102.9 ± 388.6pg/mL (ELISA) and 97.0 ± 535.5 (POC). A significant correlation was found (p < 0.0001, r = 0.92). The sensitivity/specificity for sepsis was 82.6%/86.5% (ELISA, AUC: 0.881), and 76.4%/95.0% (POC, AUC: 0.868).ConclusionsHere we demonstrate significant correlations of IL-6 levels determined using a POC test and semiautomatic ELISA. ROC analyses revealed no significant differences between the two tests. With a turn-around time of 20min, the bedside IL-6 test is a new tool that may help to initiate early goal-directed therapy.     

Particle-enhanced turbidimetric immunoassay for determination of serum neutrophil gelatinase-associated lipocalin on the Roche Cobas c501 analyzer

ObjectiveNeutrophil gelatinase-associated lipocalin (NGAL) has been reported to be a good marker for tubular damage and acute kidney injury. The aim of this study was to develop a high throughput assay for the quantification of serum NGAL (sNGAL).MethodsImprecision, interference, linearity, recovery, and reference values were evaluated on Cobas c501.ResultsThe assay was linear over the dynamic range of the study (R² = 0.9988). The total assay imprecision was below 5%. The assay recovery was estimated at 98.89%–102.61%. The assay displayed a good linearity over the range from 35 μg/L to 4250 μg/L. A typical high-dose hook effect was observed for the assay at NGAL concentration > 28,800 μg/L. No interference was observed with hemoglobin ≤ 5 g/L, bilirubin ≤ 0.3 g/L, vitamin C ≤ 0.5 g/L, sodium heparin ≤ 5 g/L and intralipid ≤ 1%. The 95th centile for serum NGAL was < 122.57 μg/L from 454 healthy donors. There were no gender-related differences for serum NGAL. There were significant age-related differences between the 21–44 and 45–75 year categories for serum NGAL. The reference value for sNGAL was < 116.52 μg/L in the 21–44 year group and < 126.9 μg/L in the 45–75 year group.ConclusionsThe NGAL assay verified to be a reliable assay with convenient performance characteristics. The assay improves and simplifies the laboratory workload.     

Is plasma neutrophil gelatinase-associated lipocalin a predictive biomarker for acute kidney injury in sepsis patients? A systematic review and meta-analysis

PurposeNeutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for early diagnosis of acute kidney injury (AKI). However, the diagnostic value of NGAL for predicting AKI in sepsis patients is unclear.MethodsMEDLINE, EMBASE, and Cochrane Library databases were searched to identify research publications.ResultsTwelve studies from 9 countries including a total of 1582 patients, of whom 315 (19.9%) developed AKI, were included in the study; plasma NGAL levels were significantly higher in adult sepsis patients with AKI than in those without AKI (mean difference, 274.65; 95% confidence interval [CI], 106.16-443.15; I² = 94%). Urine NGAL levels were not significantly different. The diagnostic odds ratio of plasma NGAL for predicting AKI in sepsis patients was 6.64 (95% CI, 3.80-11.58). The diagnostic accuracy of plasma NGAL was 0.881 (95% CI, 0.819-0.923) for sensitivity, 0.474 (95% CI, 0.367-0.582) for specificity, 0.216 (95% CI, 0.177-0.261) for positive predictive value and 0.965 (95% CI, 0.945-0.977) for negative predictive value.ConclusionPlasma NGAL has a high sensitivity and a high negative predictive value for detection of AKI in adult sepsis patients. However, its low specificity and low positive predictive value could limit its clinical utility. The usefulness of urine NGAL was not revealed in this study.     

Neutrophil gelatinase-associated lipocalin (NGAL) and cardiovascular events in patients with stable coronary artery disease

Abstract

Inflammation is an important mediator in the pathogenesis of atherosclerosis. Neutrophil gelatinase-associated lipocalin (NGAL) is a small glycoprotein secreted by neutrophils. NGAL regulates the activity of matrix metalloproteinase-9, which plays a role in plaque instability. It has therefore been hypothesised that NGAL may modulate inflammation and promote the development and progression of atherosclerosis. Our aim was to assess the predictive value of plasma NGAL in a prospective cohort study of 876 high-risk patients with stable coronary artery disease (CAD). NGAL levels were measured using the NGAL Test^TM from BioPorto Diagnostics. Clinical follow-up was performed after a median of 3.1?years. The endpoint was a combination of non-fatal acute myocardial infarction (MI), cardiovascular death (CVD), or ischaemic stroke. The NGAL concentration was (median [25;75%]: 64.3?µg/L [51.3;81.4]). The area under the receiver operating characteristic curve (AUC) was 0.56 (95% confidence interval (CI): 0.49;0.64) for the diagnosis of the composite endpoint and 0.66 (95% CI: 0.56;0.75) after adding NGAL to high-sensitive C-reactive protein (hs-CRP), leucocyte count, interleukin-6 (IL-6), calprotectin, age, sex, body mass index (BMI), diabetes mellitus, smoking and creatinine. However, the AUC for hs-CRP, leucocyte count, IL-6, calprotectin, age, sex, BMI, diabetes mellitus, smoking and creatinine without NGAL was similar at 0.66 (95% CI: 0.56;0.76). NGAL alone had no predictive value with respect to the composite endpoint of non-fatal AMI, ischaemic stroke, or CVD in stable CAD patients. NGAL did not add any predictive value to the endpoint compared with existing inflammatory biomarkers and cardiovascular risk factors.     

Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis

The neutrophil gelatinase-associated lipocalin (NGAL) has been emerging as a novel biomarker of acute kidney injury while its value in lupus nephritis is uncertain. The aim of this study was to assess urinary NGAL levels as a marker for disease activity in patients with lupus nephritis.This study included 70 systemic lupus erythematosus (SLE) patients; 50 with active lupus nephritis (LN) and 20 without as well as 20 matched controls. The neutrophil gelatinase-associated lipocalin (NGAL) in both serum and urine samples was measured by enzyme-linked immunosorbent assay (ELISA). Patients with active LN received standard treatment then assessed for response as well as the value of urinary NGAL (uNGAL). Our results revealed that, The SLE patients with or without LN had an elevated urinary NGAL as compared to controls (p?相似文献   

Effect of resistant starch type 2 on inflammatory mediators: A systematic review and meta-analysis of randomized controlled trials

BackgroundInflammation is the main cause in the development of chronic diseases. The enhancement of pro-inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) is the main risk factor in chronic diseases. Resistant starch type 2 (RS2) is non-gelatinized granules which their enzymatic hydrolysis is very low. RS2 might be able to reduce inflammatory mediators, therefore; our aim for this study was indicating RS2 effects on inflammatory mediators such as IL-6, TNF-a, and CRP among healthy and unhealthy subjects.MethodsArticles which assessed RS2 effect on IL-6, TNF-α, and hs-CRP were found by advanced search methods. Electronic databases including Google scholar, ISI web of science, SCOPUS, and PubMed, were searched up to October 2019. Treatment effect was the mean difference between changes in serum levels of inflammatory biomarkers in each arm of the clinical trials. To pool the effect of resistant starch on inflammatory biomarkers, we used random effects model.ResultsWe included eight articles in systematic review and meta-analysis. The overall effect illustrated no significant change in serum levels of hs-CRP, IL-6, and TNF-α in intervention group compared with the control group (WMD: -7.18 pg/mL, 95% CI: −27.80, 13.45; P = 0.495, I² = 100.0%, WMD: -0.003 pg/mL, 95% CI: −0.07, 0.06; P = 0.919, I² = 98.1%, WMD: -0.003 pg/mL, 95% CI: −0.004, -0.001; P < 0.0001, I² = 98.0% respectively).ConclusionIn conclusion, we found that RS2 could not reduce inflammatory mediators, but we still need more RCTs with longer intervention duration, higher dose, and studies in different countries.     

Increased levels of BPI-ANCA in patients with primary Sjögren’s syndrome are associated with lung involvement

BackgroundThe goal of this study was to investigate the association between bactericidal permeability increasing (BPI)-antineutrophil cytoplasmic antibody (ANCA) protein levels and primary Sjogren's syndrome (pSS) with lung involvement, as well as the potential diagnostic performance of BPI-ANCA.MethodsThe levels of BPI-ANCA in pSS patients with (n = 36) and without (n = 85) lung involvement were measured using a commercial ELISA kit. Serological biomarkers and cytokines were measured in these patients as well. Lung involvement was determined by high-resolution computed tomography (HRCT) and/or clinical symptoms. The diagnostic performance of lung involvement was determined by receiver operating characteristic (ROC) curves.ResultsThe percentage of neutrophils (NEUT%), neutrophil–lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), and the levels of BPI-ANCA, C-reactive protein (CRP), interleukin-2 (IL-2) and IL-6 exhibited an upward trend, while the percentage of lymphocytes (LYMP%) and albumin (ALB) level exhibited a downward trend in the lung involvement group. The combination of BPI-ANCA, NEUT% and ALB significantly increased the area under the ROC curve (AUC) to 0.837 (95% confidence interval: 0.742–0.907, sensitivity: 82.14%, specificity: 81.36%, P < 0.001).ConclusionsIncreased BPI-ANCA was found in pSS patients with lung involvement and was associated with inflammation. A combination of BPI-ANCA, NEUT% and ALB had the best AUC, and may serve as an adjunct to distinguish between pSS patients with and without lung involvement.     

Analysis of neutrophil gelatinase-associated lipocalin,vascular endothelial growth factor,and soluble receptor for advanced glycation end-products in bone marrow supernatant in hematologic malignancies

BackgroundInflammation is a known risk factor of cancer development, including inflammation-driven leukemogenesis. Evaluation of inflammation-related cytokines in early diagnosis stages is crucial to understand the development of hematologic malignancy. Our aim was to measure three cytokines- neutrophil gelatinase-associated lipocalin (NGAL), vascular endothelial growth factor (VEGF), and soluble receptor for advanced glycation end-products (sRAGE) in bone marrow (BM) samples from patients diagnosed with hematologic malignancy and compare these measurements with the control. Additionally, we evaluated whether NGAL was significantly associated with sRAGE, VEGF, and several hematological parameters.MethodsBM samples were collected from 73 patients, who were classified into myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), plasma cell neoplasm (PCN) and control groups according to the BM smear and pathology review. An immunoassay, a Luminex assay, and an enzyme-linked immunosorbent assay were used to quantitate NGAL, VEGF, and sRAGE, respectively, while all measurements of NGAL, VEGF and sRAGE were performed on BM supernatants. Data on hematological parameters were collected from medical records. Intergroup comparisons were performed using the Kruskal-Wallis H-test and Pearson Chi-Square test. Single and multiple regression analyses were performed to analyze the relationships among the parameters.ResultsThe independent factors associated with NGAL were neutrophil counts and VEGF. As for both NGAL and VEGF, the MPN (n = 23) group showed the highest level, while the MDS (n = 12) group showed low levels. NGAL levels in the AML (n = 13) and MDS groups were lower than in the control group (n = 14). The MPN group demonstrated higher VEGF levels than the AML and MDS groups. The MDS group showed lower VEGF levels than the PCN (n = 11) group. No statistical difference between the hematologic malignancy and control groups or among the hematologic malignancy groups was observed for sRAGE levels.ConclusionNGAL was related to neutrophil count and VEGF. NGAL and VEGF showed similar intergroup patterns, reflecting that NGAL was associated with VEGF.     

Annexin A2, up-regulated by IL-6, promotes the ossification of ligament fibroblasts from ankylosing spondylitis patients

BackgroundAnnexin A2, a calcium-dependent phospholipid binding protein, is involved in osteogenesis. The objective of the present study was to explore the expression of Annexin A2 in spinal ligament tissues (LT) of ankylosing spondylitis (AS) patients and determine its pathological functions.MethodsmRNA and protein expression of Annexin A2 was detected by real-time PCR and Western blotting, respectively. Interleukin-6 (IL-6) concentration in serum was assessed by enzyme linked immunosorbent assay. Alkaline phosphatase (ALP) activity was measured with ALP activity kit on a microplate reader.ResultsmRNA and protein expression of Annexin A2 in LT, and IL-6 concentration in serum were significantly increased in AS patients. Moreover, exogenous IL-6 treatment significantly up-regulated Annexin A2 expression and ALP activity. Silencing of Annexin A2 expression significantly ameliorated IL-6-induced ossification of fibroblasts from AS patients, as indicated by ALP activity, expression of proteins associated with osteogenic differentiation, including bone morphogenetic protein-2, osteocalcin and osterix, and the ratio of osteoprotegerin to receptor activator of NF-κB ligand. Further MEK inhibitor experiments suggested that Annexin A2 may exert its function through extracellular signal-related kinase pathway.ConclusionsAnnexin A2, up-regulated by IL-6, may promote ligament ossification of AS patients.     

Errors in measuring plasma free fatty acid concentrations with a popular enzymatic colorimetric kit

ObjectivesOur goal was to test whether an enzymatic, colorimetric assay, the WAKO NEFA kit, provides information equivalent to liquid chromatography (LC) LC-based measures of free fatty acid (FFA).Design & methodsWe reanalyzed nadir FFA samples from 109 volunteers from a previous study where we demonstrated that maximal suppression of FFA concentrations predicts metabolic abnormalities in humans; the results from the WAKO NEFA kit, which has been widely used for over three decades, could not replicate our findings. We conducted additional studies to directly compare results from this kit to our LC-mass spectrometry (LC/MS) method that was validated by our LC-UV detection method.ResultsPlasma samples with FFA concentrations ranging from 0.015 to 1.813 mmol/L were measured both by LC-mass spectrometry (LC/MS) and by the WAKO NEFA kit. Despite good overall agreement (R² = 0.86), the slope was significantly different from 1.0 and the intercept was significantly different from zero. The results from the kit were especially discrepant with FFA concentrations <0.200 and >1.000 mmol/L. Some of the discrepancy was related to the use of oleate as the standard solution for the kit and the substrate specificity of the kit enzymes for different fatty acids. Despite attempts to improve the kit by modifying the reaction time, sample volume and the types of standard solutions, we could not obtain a satisfactory agreement between the WAKO NEFA results and LC/MS.ConclusionsThe WAKO NEFA kit should not be used when high precision and accuracy of FFA concentrations over a wide range is required.     

Urine neutrophil gelatinase-associated lipocalin as a biomarker of adult pyelonephritis

BackgroundPyelonephritis is a common infection at any age. Urine neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute renal failure, is related to pyelonephritis in pediatric patients, although the significance of this urine biomarker in adult patients are not clear. We investigated the relationship between urine NGAL of pyelonephritis and non-pyelonephritis.Patients and methodsWe prospectively enrolled adult patients who were hospitalized due to pyelonephritis or non-pyelonephritis. Pyelonephritis was diagnosed in patients with fever and bacteriuria, with no any other infection focuses. Non-pyelonephritis was diagnosed in patients who had fever and another infection focus without bacteriuria. Urine samples were collected on days 0, 3 and 7. Urine NGAL levels were measured by ELISA.ResultsThere were 35 patients in the pyelonephritis group and 19 patients in the non-pyelonephritis group. Urine NGAL level were significantly higher in the pyelonephritis group than the non-pyelonephritis group on day 0 (median 302 ng/mL vs 25 ng/mL, p = 0.006). The area under the receiver operating characteristic curve of NGAL was 0.78 (p = 0.006). Urine NGAL level had a specificity of 66.7% and sensitivity of 87.0% at the cut-off level of 250 ng/mL for diagnosing pyelonephritis.ConclusionsUrine NGAL level at the diagnosis of infection are elevated in adult patients with pyelonephritis, but not in those with non-pyelonephritis. Urine NGAL might be a supportive biomarker for the diagnosis of pyelonephritis.     

Serum interleukin measurement may help identify thyroid cancer patients with active disease

BackgroundInvestigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease.MethodsWe evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA.ResultsAll ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p = 0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p < 0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p = 0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p < 0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness.ConclusionWe suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention.     

TNF-α及IL-1β在脓毒症性急性肾损伤中的价值及与NGAL的关系

目的 探讨炎症因子水平对脓毒症性急性肾损伤(SI-AKI)的预测价值及即时检测NGAL对监测全身炎症反应的意义.方法 共纳入脓毒症患者48例,入院后0、12、24、48、72h监测尿量及血肌酐水平,依据KDIGO标准进行SI-AKI诊断及分期,分为:KDIGO 1、KDIGO 2、KDIGO 3及无肾损伤(non-AK...     

Systemic corticosteroid as an adjunctive treatment for lower respiratory tract infection in children with severe motor and intellectual disabilities

IntroductionChildren with severe motor and intellectual disabilities (SMID) are susceptible to severe lower respiratory tract infection (LTRI). As SMID patients are prone to develop recurrent wheezing and are often diagnosed with bronchial asthma, they frequently receive systemic corticosteroids as an adjunctive treatment for LRTIs. However, the efficacy of corticosteroid therapy for LTRIs in SMID children is unclear. We investigated whether or not corticosteroid therapy was associated with better clinical outcomes for SMID children with LRTIs.MethodsOur retrospective study enrolled 217 SMID children 1–15 years old hospitalized for LTRIs. We compared the clinical characteristics and outcomes between patients with and without corticosteroid therapy.ResultsOf the 217 patients, 29 (13.3%) received corticosteroid therapy. The proportion of patients with a history of bronchial asthma was higher and LRTI was more severe in patients with corticosteroid therapy than in those without the therapy. The length of hospital stay (LOHS) was significantly longer in patients with corticosteroid therapy (median 13 days) than in those without corticosteroid therapy (median 9 days) (P = 0.02). The same tendency was shown for the LOHS in patients with severe or moderate LRTI, although not to a significant extent.ConclusionSystemic corticosteroid therapy was not associated with better clinical outcomes in SMID children with LRTIs, even if the patients suffer from severe LRTIs. Corticosteroids should be used cautiously for LRTIs in SMID children because bronchial asthma is likely to be overdiagnosed in these children.     

Pro-inflammatory interleukins in patients operated on for proximal femur fracture

Abstract

Objectives. The aims of this study were to measure plasma IL 6 and IL 8 in patients with proximal femoral fracture (PFF) during the early phases of trauma and operation and to find out if there was any correlation between these ILs and the post-operative lower limb oedema. Material and methods. Thirty patients with a median age of 81 years were grouped into pertrochanteric fracture (PTF) (n = 16) and femoral cervical fracture (FCF) (n = 14). Plasma interleukin levels were determined on blood samples obtained from the common femoral vein, immediately after hospital admission, 1 h before operation, and post-operatively at 1, 6, 12, 24, 48 h and on the 7th day. Thigh oedema was calculated by the frustum method. Results. In the patients with PTF, maximum mean plasma IL-6 and IL-8 values were found, respectively at 24 h (45.12 pg/mL) and 6 hours (21.7 pg/mL) postoperatively. Whereas, in the patients with FCF, it was respectively, at 12 h (33.1 pg/mL) and 6 h (17.0 pg/mL), for IL-6 and IL-8 post operatively. The patients with PTF and FCF had respectively, 34.1% and 27.4% more thigh oedema in the operated limb on the 7th post-operative day as compared to the preoperative oedema volume (p<0.001). No significant correlation could be found between the plasma IL-6 and IL-8 levels and oedema in the operated limb. Conclusion: Increased levels of IL 6 and IL 8 suggest ongoing inflammation.     

NGAL: an emerging tool for predicting severity of AKI is easily detected by a clinical assay

Citation

Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008, 3:665-673 [1].

Background

The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). The availability of a standardized clinical platform for NGAL measurements could revolutionize renal diagnostics, especially in intensive care situations.

Methods

Objective

The first objective of the present study was to determine whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT^® analyzer, Abbott Diagnostics) correlates with the research-based assay. The second objective was to determine the utility of the standardized NGAL immunoassay as a predictive biomarker of AKI after CPB in a large prospective cohort.

Design

Prospective cohort study

Setting

Children''s hospital at a large US academic medical center.

Subjects

196 children undergoing elective CPB for surgical correction or palliation of congenital heart lesions between January 2004 and June 2006.

Intervention

None.

Outcomes

The primary outcome variable was the development of AKI, defined as a 50% or greater increase in serum creatinine from baseline. Other outcomes included percent change in serum creatinine, days in AKI, dialysis requirement, length of hospital stay, and mortality.

Results

In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, serial urine NGAL measurements were obtained by ARCHITECT assay. Of the 196 children undergoing CPB, AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.

Conclusions

Accurate measurements of urine NGAL are obtained using the ARCHITECT^® platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.     

中性粒细胞明胶酶相关脂质运载蛋白在重症肺炎合并脓毒症患儿中的表达及临床价值

目的探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在重症肺炎合并脓毒症患儿中的表达及临床价值。方法选取该院106例重症肺炎合并脓毒症患儿,根据严重程度分为脓毒症组、严重脓毒症组和脓毒症休克组,根据出院时转归分为预后良好组和预后不良组,根据是否合并肾功能障碍分为肾功能障碍组和无肾功能障碍组。分析患儿的NGAL、降钙素原(PCT)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)及小儿危重病例评分(PCIS),采用Spearman秩相关及受试者工作特征曲线(ROC曲线)对各指标进行分析与评价。结果肾功能障碍组NGAL水平明显高于无肾功能障碍组,两组比较差异有统计学意义(P<0.05);NGAL、CRP、PCT、IL-6水平和PCIS在脓毒症组、严重脓毒症组和脓毒症休克组中的差异均有统计学意义(均P<0.05),其中NGAL、PCT、IL-6水平在3组中依次升高,PCIS在3组中依次降低,组间两两比较差异均有统计学意义(均P<0.05);与预后良好组比较,预后不良组的NGAL、CRP、PCT、IL-6水平明显升高,PCIS明显降低,差异均有统计学意义(均P<0.05);Spearman相关分析显示NGAL与CRP、PCT、IL-6呈正相关,与PCIS呈负相关(均P<0.05);NGAL用于预测预后不良的曲线下面积(AUC)为0.915,仅次于PCIS的0.949。结论NGAL在重症肺炎合并脓毒症患儿病情严重程度及预后预测中可能具有一定的临床价值。