Serum Neutrophil Gelatinase-associated Lipocalin(NGAL)Is Elevated in Patients with Asthma and Airway Obstruction

Neutrophilic airway inflammation is one of the features of severe asthma.Neutrophil gelatinase-associated lipocalin(NGAL),or lipocalin-2,is a glycoprotein associated with neutrophilic inflammation and can be detected in blood.Recently,blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease.However,the clinical significance of serum NGAL levels in patients with asthma has not been elucidated.The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma.Sixty.one non-smoking people with stable asthma were enrolled in this study.All patients underwent blood ollction and pulmonary function tests.The associations between serum NGAL levels and clinical parameters were analyzed retrospectively.Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect(76.4±51.4 ng/mL vs.39.3±27.4 ng/mL,P=0.0019).Serum NGAL levels were correlated with forced expired flow at 50%of vital capacity%predicted and forced expired flow at 75%of vital capacity%predicted(r=-0.3373,P=0.0078 and r=0.2900,P=0.0234,respectively).Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect.Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect.NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Combination of neutrophil gelatinase-associated lipocalin and matrix metalloproteinase-9 are biomarkers for the detection of colon tubular adenocarcinoma

BACKGROUND Tubular adenocarcinoma of the colon,which originates from the epithelium of the glands,is a major health concern worldwide.However,it is difficult to detect at an early stage.The lack of biomarkers is a main barrier to the diagnosis and treatment of tubular adenocarcinoma.Neutrophil gelatinase-associated lipocalin(NGAL)is a secreted protein that induces the expression of matrix metalloproteinase-9(MMP-9)and is involved in various tumors.NGAL and MMP-9 have been reported to be associated with tumorigenesis and development.They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon.AIM To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon.METHODS Samples were collected from surgically excised tissue from various patients.The content of pro-gastrin-releasing peptide(pro-GRP)in the serum was measured by an electrochemiluminescence immunoassay.The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR,Western blotting and immunohistochemical analysis.RESULTS In this study,we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy.By analyzing the expression of NGAL in tubular adenocarcinoma at different levels,we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues.The upregulation of NGAL expression was strongly correlated with both the degree of differentiation and the disease stage(I–III),indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma.When using NGAL as a biomarker for diagnosis,the accuracy was similar to that achieved with the widely used biomarker pro-GRP,suggesting that NGAL is reliable.Moreover,the expression of MMP-9 was also strongly correlated with the differentiation stage,demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon.More importantly,the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma,and these results were further confirmed by immunohistochemical analysis of tissue sections.CONCLUSION Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.

Evaluation of Reticulocyte Hemoglobin Content and Serum Neutrophil Gelatinase-Associated Lipocalin as Predictive Biomarkers of Anemia in Children on Hemodialysis

Background: Diagnosis of iron deficiency anemia with currently available tests is rendered difficult in hemodialysis patients. The aim: To investigate the role of reticulocyte Hemoglobin Content (CHr) in the diagnosis of iron deficiency anemia in hemodialysis children in comparison to the used traditional markers and assess the impressiveness and the utility of Neutrophil Gelatinase Associated Lipocalin (NGAL) as a novel biomarker of iron status in those patients. Methods: This study investigated CHr in addition to NGAL serum level in the same line with traditional markers for anemia, including: CBC, serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT%). Results: It is more significant that CHr content in hemodialysis children is lower than their controls as they are (27.06 ± 2.90) pg and (32.86 ± 3.59) pg, respectively, p = 0.01. There is no significant difference regarding NGAL between the study groups. Significant negative correlation between CHr with ferritin, urea, creatinine, and positively correlated with iron and RBCS. CHr showed a sensitivity of 90% and specificity of 86.67% to detect iron-deficiency anemia with a cut-off value of 27 pg. Conclusion: CHr is superior to ferritin and TSAT % for the early diagnosis of iron deficiency anemia in hemodialysis children;our results do not support NGAL as a marker of anemia in hemodialysis patients.

Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure

BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical settings.AIM To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of CRS-1.METHODS We performed a retrospective cohort,multi-centre study.From January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary syndrome.We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.RESULTS Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required dialysis.Neither the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak value.Finally,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly correlated.CONCLUSION In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart disease.So,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

The Differences of Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels between Asphyxiated and Non-Asphyxiated Neonates

Objective: To evaluate the differences of urinary NGAL levels between asphyxiated and non-as- phyxiated neonates. Methods: This was a cross-sectional observational analytic study, including 34 newborns in Dr. Hasan Sadikin Hospital, Bandung, Indonesia. Sample collection was conducted from December 2014 to March 2015. Urine NGAL levels were evaluated using enzyme-linked immunosorbent assays (ELISA) technique. To determine the differences of urinary NGAL levels between asphyxiated and non-asphyxiated group we used Mann-Whitney U test, and to determine the differences of gestational age and birth weight between these two groups we used Fisher’s exact test. Results: Twenty males (60%) and 14 females (40%) neonates participated in the study. From 34 subjects, 17 neonates were diagnosed with asphyxia and 17 neonates without asphyxia. The results showed that urine NGAL levels had significantly increased in asphyxiated neonates. The median urine NGAL level in asphyxiated group is 95% CI: 506.7 (60.0 - 651.7) ng/mL, while the median urine NGAL level in non-asphyxiated group is 95% CI: 6.7 (0.1 - 53.0) ng/mL. Statistically, there were significant urine NGAL levels differences between asphyxiated and non-asphyxi- ated neonates (p < 0.001). There were no differences in gestational age and birth weight between asphyxiated and non-asphyxiated neonates (p > 0.05). Conclusions: Urinary NGAL levels in asphyxiated neonates were significantly higher than those in non-asphyxiated neonates. There were significant differences of urine NGAL levels between the groups.

Urinary neutrophil gelatinase-associated lipocalin(NGAL)and serum cystatin C measurements for early diagnosis of acute kidney injury in children admitted to PICU

Background Acute kidney injury(AKI)is common in critically ill children with significant mortality and morbidity.Serum creatinine is an insensitive and late biomarker compared to newly proposed AKI biomarkers.Methods Prospective study in pediatric intensive care unit(PICU)over three months to compare between serum cystatin-C(s-Cys-C)and urinary neutrophil gelatinase-associated lipocalin(uNGAL)as AKI biomarkers at multiple time points with pediatric risk,injury,failure,loss,end-stage renal disease(pRIFLE)classification in diagnosing AKI.Results Forty children were recruited.Of these 40 children,22 developed AKI according to pRIFLE criteria.There was no significant difference between AKI and non-AKI in age(P=0.29).Post cardiac surgery,renal insult was the main cause of AKI(27.3%).There was a twofold increased risk of incident AKI in those patients with high baseline uNGAL at PICU admission and almost a fourfold increased risk in patients with high baseline s-Cys-C at PICU admission.uNGAL levels were highly predictive of AKI during the follow-up period[area under the curve(AUC)=0.76,95%confidence interval(CI)0.61-0.92].The cutoff point with the highest correctly classified proportion was 223 ng/mL(≥12 centiles)which correctly predict 80.0%patients with AKI,with a corresponding sensitivity of 72.7%and a specificity of 89.9%.AUC for s-Cys-C was 0.86(95%CI 0.75-0.97),and the highest correctly classified proportion was 1009μg/L(≥13 centiles);75%of patients with AKI,with a corresponding sensitivity of 63.6%and a specificity of 88.9%.Conclusion uNGAL and s-Cys-C predicts AKI early in critically ill children.

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi Compatibility on Uric Acid Metabolism and Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Rats with Hyperuricemia

Objective：To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomicompatibility（PR） on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin（NGAL） and kidney injury molecule-1（KIM-1） in rats with hyperuricemia. Methods：Seventy male Sprague Dawley（SD） rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses（3.5, 7, 14 g/kg）. Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid（SUA）, blood urea nitrogen（BUN） and creatinine（Cr） were determined. In addition, the contents of NGAL and KIM-1 in urine and the m RNA and protein expressions of xanthine oxidase（XOD） in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction（RT-PCR） and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin（HE） stain method. Results：Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD m RNA and protein in the hyperuricemia rats were increased significantly（P〈0.01）. PR significantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the m RNA and protein expressions of hepatic XOD（P〈0.05 or P〈0.01）. In addition, the pathological changes of kidney were significantly suppressed by oral administration of PR. Conclusions：PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

Urine neutrophil gelatinase-associated lipocalin at SICU admission predicts for cardiac surgery-associated acute kidney injury

Background Acute Kidney Injury （AKI） is a common and serious complication of cardiovascular surgery. There is a need to find biomarkers that are involved in the etiology of cardiac surgery-associated acute kidney injury （CSA-AKI） and have an earlier response to acute kidney injury. The association between urine neutrophil gelatinase-associated lipocalin （NGAL） concentrations and AKI progression is not well established. Methods The prospective-cohort study included 1631 consecutive adult patients undergoing cardiac surgery at Fuwai Hospital between September 2012 and November 2013. AKI defined by Acute Kidney Injury Network （AKIN） criteria with a postoperative increase in plasma creatinine 〉/50% baseline or/〉0.3 mg/dL. Urine NGAL was measured us- ing latex particle-enhanced turbidimetric immunoassay. Associations between Urine NGAL levels and AKI were determined by estimating areas under receiver operating characteristic curves （AUC）. Results A total of 438 （26.9%） patients developed CSA-AKI. And the patients were divided into four groups： 1193 non-AKI patients, 368（22.6%） patients with AKIN stage I AKI, 49（3.0%） with AKIN stage 2 AKI and 21（1.3%） with AKIN stage 3 AKI. urine NGAL concentrations at surgical intensive care unit （SICU） admission were significantly related to AKI severity. The AUCs for urine NGAL were for AKIN stage 1 （0.54±0.02）, AKIN stage 2 （0.67±0.04）, and AKIN stage 3 （0.76±0.06）, respectively. Conclusions Urinary NGAL is associated with CSA-AKI and its progression, indicating their potential use as prognostic markers. Urine NGAL level measured at SICU admission predicts the development of severe AKI after cardiac surgery.

Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

Background: Neuttrophil gelatinase associated lipocalin (NGAL) was shown to be a good marker for predicting acute kidney injury (AKI). Some recent reports demonstrated that NGAL may be an early biomarker for kidney affection in diabetic patients. The aim of this work is to investigate urinary NGAL (UNGAL) in type 2 diabetic patients with and without albuminuria. Methods: This study included 46 type 2 diabetic patients and 15 healthy age and sex matched individuals as the control group. Diabetic patients were divided into three groups according to urinary albumin excretion (UAE), normoalbuminuria, microalbuminuria and macroalbuminuria. UNGAL was measured in all populations and corrected to urinary creatinine to account for day to day variation in urine volume and transformed log. Comparison between 4 groups (control, normoalbuminuria, microalbuminuria and macroalbuminuria) was done. Results: Log UNGAL/Creatinine ratio showed significant difference when comparing control group (0.70 ± 0.58) versus normoalbuminuria (1.71 ± 1.06), microalbuminuria (1.57 ± 0.72) and macroalbuminuria (1.92 ± 0.63), however, there was no significant difference among diabetic groups. Pearson’s correlation showed that log UNGAL/Creatinine ratio positively correlated with glycated hemoglobin (HbA1c) and inversely with estimated glomerular filtration rate (eGFR). Regression analysis showed that HbA1c, urinary creatinine and eGFR were the independent predictors of log UNGAL/Creatinine ratio. Conclusion: Tubular markers like UNGAL may be early elevated in type 2 diabetic patients even before the incidence of glomerular injury detected by microalbuminuria and it can be used as an early marker for detection of kidney involvement in diabetic patients.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

AIM: To evaluate neutrophil gelatinase associated lipocalin(NGAL) in patients infected by hepatitis C virus(HCV) before and during treatment with directly acting antivirals(DAAs).METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate(e GFR). Then, NGAL and e GFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for nonparametric data. Differences in dichotomous variables were evaluated through χ~2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four(FIB-4), AST to platelet ratio index(APRI), and e GFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with e GFR < 60 mL/min vs patients with e GFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/d L were compared with those of NGAL ≤ 118.11 ng/d L, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis(P > 0.05). Linear correlation was found between NGAL and both age(P = 0.0475) and e GFR(P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for e GFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline(P = 0.0239).CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

Levels of neutrophil gelatinase-assosciated lipocalin in patients with head and neck squamous cell carcinoma in Indian population from Haryana state

AIM To study the levels of neutrophil gelatinase associated lipocalin(NGAL) in head and neck squamous cell carcinoma(HNSCC).METHODS This was a non randomized case control study conducted at Department of Biochemistry,in collaboration with Regional Cancer Center over a period of one year.The study population included 50 adult newly diagnosed HNSCC patients reporting in outpatient department at Regional Cancer Center and compared with 50 healthy controls.NGAL was estimated by ELISA technique.Student t test and χ~2 test were applied for comparison of means of study groups.Correlations between groups were analyzed using Pearson correlation coefficient(r) formula.RESULTS Patients with HNSCC exhibited significantly increased levels of NGAL(P < 0.05) as compared to healthy controls(978.88 ± 261.39 ng/mL vs 34.83 ± 7.59 ng/mL).Out of 50,26 patients(52%) were in stage Ⅳ,21(42%) in stage Ⅲ,1(2%) patient in stage Ⅱ and 2(4%) patients were in stage Ⅰ.Metastasis was absent in 98% patients and mean NGAL levels were highest in these patients but P value was not significant.Mean NGAL levels were highest in stage Ⅳ [1041.54 ± 222.15 ng/mL(stage Ⅳ) vs 1040 ± 0.00 ng/mL(stage Ⅰ);900 ± 0.00 ng/mL(stage Ⅱ) and 1031.90 ± 202.55 ng/mL(stage Ⅲ)] and χ~2 test was highly significant(P < 0.001).Thirty-six patients(72%) were having moderately differentiated HNSCC and mean NGAL levels were maximum in patients with well differentiated HNSCC(1164 ± 315.64 ng/mL vs 1013.33 ± 161.19 ng/mL in moderately differentiated and 890 ± 11.55 ng/mL in poorly differentiated) and the results were also highly significant(P < 0.001,χ~2 test).CONCLUSION The present work demonstrates a potential role of NGAL as cancer biomarker and its use in monitoring the HNSCC progression.

Correlation between Serum Neutrophil Gelatinase Associated Lipocalin and Burn Severity: A Pilot Study

The severity of an initial burn injury is critical for determining the treatment plan and prognosis of burn patients. Here, we measured serum neutrophil gelatinase-associated lipocalin (NGAL) levels to determine whether NGAL can be used as a biomarker for severity of burn injuries. A study of the demographic, clinical, and laboratory markers for various organ damage was performed at Bestian Burn Center (n = 10 healthy people, n = 31 patients). NGAL and organ damage marker levels were measured in 31 patients with severe burns within 2 - 3 days following their admission to the intensive care unit. Serum NGAL level of the expired patients was 788.5 (685.0 - 998.0) pg/mL, whereas that of the discharged patients was 421.2 (356.2 - 480.6) pg/mL, showing that the initial serum NGAL level can be used to estimate mortality. We also determined the correlation between serum NGAL level and the currently used severity markers (total body surface area burned and abbreviated burn severity index) and confirmed that serum NGAL level could be used as a severity marker. We also found that serum NGAL level was correlated with damage of organs such as the liver, kidney, heart, and respiratory organs in patients with severe burns.

Study of Lipocalin-2 Associated with Neutrophilic Gelatinases (uNGAL) in the Urine in Children with the Microbial Inflammatory Diseases of Kidneys and Urinary Tract

Purpose of the study: Research of the clinical and diagnostic significance of determination of Lipocalin-2 associated with neutrophilic gelatinases (uNGAL) in the urine of children with urinary tract infection (UTI) and pyelonephritis. Materials and methods: We examined 30 children with acute pyelonephritis and UTI aged 1 to 16 years (average age 7.32 ± 4.52) including 26 girls and 4 boys. Verification of the diagnosis was conducted on the basis of clinical and laboratory data, medical history and instrumental examination of patients. All children were divided into 2 groups: 1st group—15 children with acute pyelonephritis, 2nd group—15 children with urinary tract infection. uNGAL was measured in the urine by enzyme-linked immunosorbent assay (EISA) (BioVendor Laboratoty Medicine). Results: It is found, that the urine level of NGAL depends on the damage degree of renal parenchyma. The correlation of medium strength was found between the excretion level of uNGAL during the acute period of pyelonephritis and the detection of renal scars according to the DMSA-nephroscintigraphy data. In the group of children with the acute pyelonephritis the direct correlation of medium strength was found between the excretion level of uNGAL/creatinine and leukocytosis value and also with the CRP blood level. Conclusion: The results allow us to recommend the determination of the excretion level of uNGAL/creatinine as an additional non-invasive marker for the early detection of renal parenchyma injury.

Plasma neutrophil-gelatinase-associated lipocalin and cystatin C could early diagnose contrast-induced acute kidney injury in patients with renal insufficiency undergoing an elective percutaneous coronary intervention

Background Contrast induced acute kidney injury （CIAKI） is an important complication in the use of iodinated contrast media （CM）. Our study was to evaluate the neutrophil gelatinase-associated lipocalin （NGAL） and cystatin C for early diagnosis of CIAKI. Methods The patients with established or suspected coronary artery disease （CAD） with the estimated glomerular filtration rate （eGFR） was more than 30 ml·min^-1·1.73 m^-2 and nor more than 90 ml·min^-1·1.73 m^-2 were continuously enrolled. The blood samples of the first 50 patients were obtained before and at 2, 4, 8, 24 and 48 hours after procedure to identify the time points at which the biomarkers reached peaks and at which the blood samples of the rest of patients were obtained. The plasma NGAL and cystatin C measure used enzyme-linked immunosorbent assay （ELISA） kit. The diagnostic characteristics of absolute and relative increasing NGAL and cystatin C for CIAKI were evaluated. Results Total 311 patients were enrolled, among whom 39 （12.5%） developed CIAKI. Plasma NGAL increased at 2 hours and reached peak at 4 hours after procedure, while plasma cystatin C increased at 2 hours and reached peak at 24 hours after procedure. Thus, we determine rational point of time at 4 hours for NGAL and at 24 hours after procedure for cystatin C, respectively. The plasma NGAL at 4 hours after CM exposure showed largest area under curve （AUC） of 0.662 （95% confidence interval （CI）： 0.565-0.758, P=0.002） with 51.5% sensitivity and 80.6% of specificity. The relative increasing 25% of NGAL showed the best sensitivity and specificity of 0.872 and 0.808, respectively, with maximum Youden index of 0.680, while cystatin C with relative increasing more than 25% had 76.9% of sensitivity and 81.2% of specificity. Combined two biomarkers might get more than 90% of specificity. Conclusions Single measurement of NGAL or cystatin C had poor sensitivity and specificity; however, the relative increasing 25% of NGAL at 4 hours after CM exposure demonstrated higher diagnostic values for CIAKI. Combining relative increasing plasma NGAL with relative increasing plasma cystatin C might perform better for early diagnosis of CIAKI.

急、慢性肾损伤患者血清中生物标志物的研究与验证

目的:探讨血清中中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)及其他生物标志物在急、慢性肾损伤患者中的临床应用价值。方法:选取2022年1月~2023年7月在广州市中山大学附属第三医院就诊的急性肾损伤(acute kidney injury,AKI)患者171例及慢性肾脏病(chronic kidney disease,CKD)患者209例。收集各组成员的钾(K)、钠(Na)、氯(Cl)、二氧化碳(CO_(2))、尿素(Urea)和葡萄糖(GLU)数据。选取同时期健康体检者94例作为健康对照组,并用胶乳免疫比浊法检测3组成员血清中的NGAL水平。分析血清NGAL和其他生物标志物在鉴定急性和慢性肾损伤中的诊断有效性。采用多因素logistic回归方程分析影响AKI和CKD患者发生的因素。此外,还构建了受试者工作特征(receiver operating characteristic,ROC)曲线,以评估这些生物标志物在肾损伤患者中的临床意义。结果:通过生物信息学分析,提示NGAL可能是肾损伤的检测标志物。一般资料显示,在AKI组及CKD组中,K、Na、CO_(2)、Urea、GLU和NGAL水平均高于健康对照组(P<0.05)。多因素logistic回归方程分析显示,Na、Urea、GLU和NGAL水平均为AKI或者CKD疾病发生的独立危险因素(P<0.05)。ROC曲线分析结果显示,在AKI组中,Na、Urea、GLU和NGAL的曲线下面积(area under curve,AUC)分别为0.711、0.960、0.793和0.841(P<0.01);在CKD组中,Na、Urea、GLU和NGAL的AUC分别为0.681、0.990、0.703和0.930(P<0.01)。NGAL和Urea联合诊断AKI的灵敏度和特异性分别是81.9%和61.1%,诊断CKD的灵敏度和特异性分别是62.7%和80.0%。结论:血清NGAL可作为急、慢性肾损伤的指标,联合其他生物标志物在急、慢性肾损伤中也有一定的临床应用价值。

尿液中性粒细胞明胶酶相关脂质运载蛋白和白细胞介素-6水平对心脏外科术后患者严重液体超负荷的风险价值

目的分析尿液中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和白细胞介素-6(IL-6)水平对心脏外科术后患者严重液体超负荷(FO)的风险价值。方法选取2020年4月—2023年3月在成都市第三人民医院接受心脏外科手术的患者220例,根据术后24 h FO,将FO≥10%的患者记为A组,将FO<10%的患者记为B组。分析两组一般资料,比较两组术前及术后尿液NGAL和IL-6水平,采用logistic回归模型分析心脏外科术后24 h内患者发生严重FO的危险因素,绘制ROC曲线,分析尿液NGAL、IL-6对患者发生严重FO的风险价值。亚组分析不同原发病对FO的影响。结果A组男性ICU停留时间比例高于B组(P<0.05),术前白蛋白水平及术后当天尿量低于B组(P<0.05),两组体重指数、年龄、病程、手术时间、术中尿量、原发疾病类型、术前左室射血分数、肌酐水平、白细胞计数、血红蛋白水平、机械通气时间、体外循环时间,以及急性肾损伤、左心功能不全、高血压、心力衰竭、糖尿病占比比较无差异(P>0.05);两组术后2 h、术后12 h尿液NGAL和IL-6水平均高于术前(P<0.05),术后12 h尿液NGAL和IL-6水平均高于术后2 h(P<0.05),且A组术前、术后2 h及术后12 h均高于B组(P<0.05);logistic回归分析发现,术前尿液NGAL和IL-6水平高是心脏外科术后患者发生严重FO的危险因素(P<0.05);ROC结果显示,术前尿液NGAL和IL-6水平对心脏外科术后患者发生严重FO的最佳截断点分别为48.04 ng/mL和32.26 pg/mL,AUC分别为0.865和0.704,二者联合检测AUC为0.894。冠心病、先天性心脏病、心脏瓣膜病亚组之间FO情况、ICU停留时间、体外循环时间、术后当天尿量及术前NGAL和IL-6之间无显著差异(P均>0.05)。结论心脏外科术后患者尿液NGAL和IL-6水平异常升高,术前尿液NGAL和IL-6水平是其发生严重FO的危险因素。

血清PTX3 SFRP4联合尿NGAL对糖尿病肾病的诊断价值

目的:探讨联合检测尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)及血清正五聚蛋白3(PTX3)和分泌型卷曲相关蛋白4(SFRP4)对临床上糖尿病肾病(DN)的诊断意义。方法:选取我院2020年12月至2023年6月就诊的DN患者86例,作为DN组,根据尿微量白蛋白排泄率(UAER)分为早期组(24例,UAER≤20μg/min)、中期组(30例,20μg/min<UAER<200μg/min)、晚期组(32例,UAER≥200μg/min),根据病情严重程度分为轻度DN组(40例)和中重度DN组(46例),另选取40例单纯2型糖尿病患者为对照组。比较DN组与对照组、不同病情程度组以及早中晚期组血清PTX3、SFRP4和尿液NGAL水平。分析三者及其联合检测在诊断DN中的临床价值。结果:DN组血清PTX3、SFRP4和尿液中NGAL的水平均高于对照组(P<0.05);与轻度DN组相比中重度DN组患者三个指标的水平也明显升高(P<0.05);中、晚期组DN患者三个指标的水平较早期组升高(P<0.05)。ROC曲线分析显示,三者联合诊断DN的曲线下面积(AUC)为0.985,且联合诊断AUC大于单一指标诊断(Z三者联合-PTX3=2.670、Z三者联合-SFRP4=3.976、Z三者联合-NGAL=2.510,P=0.008、0.000、0.012),敏感度为94.20%,特异性为96.00%。结论:血清PTX3、SFRP4和尿液NGAL联合检测在诊断DN以及评估DN患者严重程度具有更高的可靠性。

生物标志物在脓毒症相关急性肾损伤中的应用

月毒症相关急性肾损伤(SA-AKI)是脓毒症常见并发症之一,是脓毒症所致的与长期不良后果相关的一种急性功能及器官损害综合征,其发病率呈逐渐上升趋势,且病死率远高于单纯脓毒症。利用生物标志物早期识别SA-AKI和预测疾病进展并给予相应的干预措施,对于降低SA-AKI死亡风险及长期后遗症的发生至关重要。截止目前,鲜见可特异性识别SA-AKI的生物标志物被提出,临床仍以急性肾损伤(AKI)相关生物标志物来识别SA-AKI的发生或预测其进展,因此,了解生物标志物在AKI与SA-AKI发生或变化中的差异所在,是评估AKI相关生物标志物在识别SA-AKI发生及预测其进展中的关键环节。现通过概述AKI相关生物标志物在AKI与SA-AKI发生发展中的差异,为识别SA-AKI发生及预测其进展的生物标志物提供参考。

CD4^(+)/CD8^(+)、NGAL和SAA与老年肾衰竭血液透析患者细菌感染的相关性及诊断价值

目的 研究外周血CD4^(+)/CD8^(+)、人中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase associated lipocalin,NGAL)和淀粉样蛋白A(serum amyloid A protein,SAA)与接受维持性血液透析(maintenance hemodialysis,MHD)治疗的老年慢性肾衰竭(chronic renal failure,CRF)患者细菌感染的相关性及其诊断价值。方法 选取2019年10月—2021年10月在海南省中医院接受MHD治疗的老年CRF患者合并细菌感染者61例(感染组)和未合并感染者104例(非感染组)为样本开展横断面研究,检测2组CD4^(+)/CD8^(+)、NGAL和SAA表达水平并进行比较,建立Logistics回归模型分析各指标与老年CRF患者MHD治疗期间细菌感染的关系并作受试者工作特征(ROC)曲线分析其诊断价值。结果 感染组CD8^(+)(t=2.573,P=0.011)、NGAL(t=6.670,P<0.001)和SAA(t=10.116,P<0.001)表达水平高于非感染组,CD4^(+)(t=8.514,P<0.001)、CD4^(+)/CD8^(+)(t=3.904,P<0.001)表达水平低于非感染组。校正年龄、性别和透析龄等基本资料后进行Logistics回归分析(因变量赋值感染组=1,非感染组=0)显示CD4^(+)/CD8^(+)(OR=0.586,95%CI:0.440~0.780,P<0.001)、NGAL(OR=1.324,95%CI:1.149~1.525,P<0.001)和SAA(OR=1.419,95%CI:1.251~1.610,P<0.001)均与老年CRF患者MHD治疗期间细菌感染存在密切联系;ROC曲线分析显示CD4^(+)/CD8^(+)、NGAL和SAA用于老年MHD患者细菌感染诊断的曲线下面积(AUC)分别为0.576、0.738和0.838,敏感度分别为54.10%、62.30%和77.05%,特异度分别为63.46%、83.65%和77.88%,将3项指标建立Logistics回归模型进行综合判断,结果显示AUC为0.886,敏感度为85.25%,特异度为79.81%。结论 接受MHD治疗的老年CRF患者外周血CD4^(+)/CD8^(+)、NGAL和SAA与细菌感染存在密切联系,检测CD4^(+)/CD8^(+)、NGAL和SAA表达水平变化可为细菌感染早期准确诊断提供参考依据。

替格瑞洛在STEMI患者介入术后中的应用及对血清NGAL、MMP-9水平的影响

目的分析替格瑞洛在急性ST段抬高型心肌梗死(STEMI)患者介入术后的应用及对血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、基质金属蛋白酶-9(MMP-9)水平的影响。方法选定2020年1月至2022年1月住院的86例STEMI介入术患者,以随机法将其分为2组,每组43例。氯吡格雷组给予氯吡格雷治疗,替格瑞洛组给予替格瑞洛治疗,比较2组心肌损伤标志物、血清NGAL、MMP-9水平、TIMI血流分级、主要心血管不良事件(MACE)总发生率、不良反应总发生率。结果替格瑞洛组治疗后血清肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、NGAL、MMP-9水平均比氯吡格雷组低(P<0.05)。替格瑞洛组治疗后TIMI血流分级优于氯吡格雷组(P<0.05)。替格瑞洛组MACE总发生率(2.33%)低于氯吡格雷组(16.28%)(P<0.05)。替格瑞洛组MACE总发生率(4.65%)低于氯吡格雷组(9.30%),差异无统计学意义(P>0.05)。结论STEMI患者介入术后给予替格瑞洛,可有效减轻心肌细胞受损程度及冠脉硬化程度,改善血流分级,降低MACE发生率,且未见明显不良反应,具有一定的安全性。