Serum Lipocalin-2 Levels as a Biomarker in Pre- and Post-Pubertal Klinefelter Syndrome Patients: A Pilot Study.

Klinefelter syndrome (KS) is a male genetic disease caused by the presence of an extra X chromosome, causing endocrine disorders mainly responsible for a high rate of infertility and metabolic disorders in adulthood. Scientific research is interested in identifying new biomarkers that can be predictive or prognostic of alterations strictly connected to KS. Lipocalin-2 (LCN-2, also known as NGAL) is a small protein initially identified within neutrophils as a protein related to innate immunity. Serum LCN-2 estimation seems to be a useful tool in predicting the metabolic complications caused by several pathological conditions. However, little is known about its potential role in infertility conditions. The present pilot study aims to investigate the presence of LCN-2 in the serum of a group of pre-pubertal and post-pubertal children affected by KS, compared to healthy controls. We demonstrated for the first time the presence of elevated levels of LCN-2 in the serum of KS patients, compared to controls. This increase was accompanied, in pre-pubertal KS patients, by the loss of correlation with LH and HDL, which instead was present in the healthy individuals. Moreover, in all KS individuals, a positive correlation between LCN-2 and inhibin B serum concentration was found. Despite the limited size of the sample analyzed, our preliminary data encourage further studies to confirm the findings and to extend the study to KS adult patients, to verify the predictive/prognostic value of LCN-2 as new biomarker for metabolic diseases and infertility associated with the pathology.

Neutrophil gelatinase-associated lipocalin serum level: A potential noninvasive biomarker of endometriosis?

Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2) is an acute-phase protein expressed in many tissues and plays a role in cell proliferation, regulation, and epithelial-mesenchymal transformation. Therefore, this study aimed to investigate serum NGAL levels and endometrioma tissue expression in women with endometriosis. This cross-sectional study was conducted at a university hospital. The endometrioma group included 36 women who underwent ovarian cystectomy for endometrioma, which was compared with a control group (n = 36) of women who underwent ovarian cystectomy due to benign persistent cysts (follicle cyst, theca lutein cyst, and serous cystadenoma). NGAL levels were analyzed using both serum enzyme-linked immunosorbent assay analysis and immunohistochemical tissue staining. Serum C-reactive protein and CA-125 levels were also evaluated. NGAL serum levels were significantly higher in the endometrioma group than in the control group (P < .05). C-reactive protein and CA-125 levels were also significantly higher in the endometrioma group (P < .05) and were correlated with NGAL levels. Immunohistochemical staining for NGAL was also higher in the endometrioma group (P < .001). NGAL may be considered a potential noninvasive biomarker of endometriosis.

Predictive Value of Serum NGAL and ß2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury.

OBJECTIVE: This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and ß2 microglobulin (ß2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). METHODS: The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and ß2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and ß2-MG in the blood and urine of patients with AKI and AP. RESULTS: The AKI group had higher serum NGAL and ß2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and ß2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. CONCLUSIONS: The increased levels of serum NGAL and ß2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI.

Predictive Value of Serum NGAL and B2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury

Objective: This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and β2 microglobulin (β2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). Methods: The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and β2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and β2-MG in the blood and urine of patients with AKI and AP. Results: The AKI group had higher serum NGAL and β2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and β2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. Conclusions: The increased levels of serum NGAL and β2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI (AU)

Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of gestational diabetes mellitus.

Objective: Gestational diabetes mellitus (GDM) has adverse effects on the health of mothers and their offspring. Currently, no known biomarker has been proven to have sufficient validity for the prediction of GDM in the first trimester of pregnancy. The aim of this study was to investigate the potential relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) levels in the first trimester of pregnancy and later GDM risk and to evaluate the performance of serum NGAL as a biomarker for the prediction of GDM. Methods: The study was conducted by recruiting participants at 8-13 weeks of gestation from The First Affiliated Hospital of Chengdu Medical College between January and June 2021; participants were followed up for oral glucose tolerance test (OGTT) screening at 24-28 gestational weeks. We examined the serum NGAL levels of all subjects in the first trimester who met the inclusion and exclusion criteria. Anthropometric, clinical, and laboratory parameters of the study subjects were obtained during the same study period. A logistic regression model was carried out to investigate the potential relationship between serum NGAL levels in the first trimester of pregnancy and later GDM risk. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the discrimination and calibration of serum NGAL as a biomarker for the prediction of GDM in the first trimester of pregnancy. Results: Serum NGAL levels in the first trimester of pregnancy were significantly higher in women who later developed GDM than in those who did not develop GDM. Serum NGAL levels in the first trimester of pregnancy were positively associated with an increased risk of GDM after adjustment for potential confounding factors. The risk prediction model for GDM constructed by using serum NGAL levels in the first trimester of pregnancy achieved excellent performance. Conclusions: Maternal serum NGAL in the first trimester of pregnancy is a potential biomarker for the prediction of GDM, which could help guide the clinical practice of antenatal care.

[Effects and significance of continuous hemoperfusion on patients with diquat poisoning].

OBJECTIVE: To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance. METHODS: A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. RESULTS: Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (µg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (µmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ 2 = 7.288, P = 0.007]. CONCLUSIONS: Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

The Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Biomarker for Monitoring Renal Function in Patients with Solitary Kidney Stones: A Single-Center, Retrospective Analysis of 23 Cases

Purpose: To assess the efficacy of flexible ureteroscopy (F-URS) in treating single kidney stones and the role of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in detecting early renal function abnormalities in patients with solitary kidney stones. Materials and Methods: We retrospectively analyzed 23 patients with solitary kidney nephrolithiasis who underwent F-URS atthe Sichuan Science City Hospital between January 2017 and November 2020. We collected data on the following variables:Age, gender, stone size, surgery time, perioperative outcomes, and complications; Stone-free rates (SFRs) were calculated using computed tomography (CT). Serum creatinine (SCr) and NGAL levels were tested before surgery and at one-day and one-month postoperatively. Results: The average size of the stones was 1.53 ± 0.57 cm. The average operating time was 59.28 ± 21.25 minutes. For , three patients (13.0%) required second-stage F-URS. The SFRs were 91.3% following the first and second treatments.The mean NGAL levels were significantly increased at one-day postoperatively compared to baseline (768.91 ± 514.50 ng/mL vs.173.39 ± 147.94 ng/mL, respectively, p < 0.001). Minor complications, including gross hematuria (n = 5) and mild fever (n = 3), occurred in 34.8% of cases (n = 8), who recovered quickly. Conclusions: F-URS is a safe and efficient therapeutic approach for patients with solitary kidney nephrolithiasis, and NGAL hashuge pro spects as an indicator of early-stage renal injury in this patient population.(AU)

Association Of Blood Lipocalin-2 Levels with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Lipocalin-2 (LCN2) is becoming recognized as a pleiotropic mediator of metabolic disorders. However, the relationship between LCN2 and gestational diabetes mellitus (GDM) is not well understood. We performed a systematic review and meta-analysis to explore it. A systematic search of Cochrane Library, PubMed, Embase, Scopus, Web of Science, Chinese National Knowledge Infrastructure, and Wan-fang Database was done for relevant articles published up to September 29, 2021. Standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated to explore the association of LCN2 levels with GDM using Revman 5.3 and Stata 15.1. Fifteen case-control studies were included in this meta-analysis. The patients with GDM had significantly higher levels of blood LCN2 than parturients with normal glucose tolerance (SMD=3.41, 95% CI=2.24 to 4.58). Meta-regression and subgroup analysis were conducted to investigate the source of heterogeneity. Likely sources of heterogeneity were age and testing methods. This study found that GDM showed higher blood LCN2 levels than controls. However, caution is warranted on the interpretation of these findings. Standardized LCN2 measurement methods and longitudinal studies are required to disentangle and better understand the relationships observed.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cystatin C are early biomarkers of acute kidney injury associated with cardiac surgery.

Acute kidney injury (AKI) is a serious complication in as much as half of the patients undergoing cardiac surgery, and early diagnosis and treatment are of the utmost importance. There is a need for robust biomarkers that can detect cardiac surgery-associated AKI (CSA-AKI) prior to rise in plasma creatinine, which typically occurs at least 48 h postoperatively. We compared pre- and 4, 12 and 48 h postoperative plasma (P) neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, urea and creatinine, and urine (U) NGAL, as markers of AKI, in 49 patients (67% men, median age 65 years) scheduled for elective cardiac surgery (e.g. coronary artery bypass graft and/or valve replacement surgery) with the use of extracorporeal circulation. Patients with preoperative sepsis, renal replacement therapy, or estimated glomerular filtration rate <30 mL/min/1.73m2 were excluded. P- and U-NGAL were measured using the Roche Modular P (Roche Diagnostics®) NGAL immunoassay. According to AKIN/KDIGO criteria, nine patients (18%) were diagnosed with CSA-AKI. Compared to patients without CSA-AKI, these patients had significantly higher P-NGAL and P-cystatin C values 4 h (p-values .002 and <.001) and 12 h (p-values <.001 and <.001) postoperatively. The same differences were not observed for U-NGAL. Patients with AKI also had significantly higher P-creatinine 4 and 12 h postoperatively (p-values .001 and <.001), however the rise in P-creatinine was just above the upper reference limit. In conclusion, plasma NGAL and cystatin C seem to detect CSA-AKI earlier than the more commonly used biomarkers creatinine and urea.

Lipocalin-2 and insulin as new biomarkers of alopecia areata.

Lipocalin-2 and visfatin are proinflammatory adipokines involved in the regulation of glucose homeostasis. Their role has been described in numerous inflammatory skin diseases such as atopic dermatitis and psoriasis. Recently, an increased prevalence of metabolic abnormalities has been reported in patients with alopecia areata. The aim of the study is to determine the serum levels of lipocalin-2 and visfatin in patients with alopecia areata in comparison with healthy controls. Moreover, the serum levels of total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, fasting glucose, insulin, c-peptide, and homeostasis model assessment for insulin resistance (HOMA-IR) were evaluated. Fifty-two patients with alopecia areata and 17 control subjects were enrolled in the study. The serum levels of lipocalin-2 [mean ± standard deviation, SD: 224.55 ± 53.58 ng/ml vs. 188.64 ± 44.75, p = 0.01], insulin [median (interquartile range, IQR): 6.85 (4.7-9.8) µIU/ml vs. 4.5 (3.5-6.6), p<0.05], c-peptide [median (IQR): 1.63 (1.23-2.36) ng/ml vs. 1.37 (1.1-1.58), p<0.05)], and HOMA-IR [median (IQR): 1.44 (0.98-2.15) vs. 0.92 (0.79-1.44), p<0.05) were significantly higher in patients with alopecia areata compared to the controls. The serum concentration of insulin and HOMA-IR correlated with the number of hair loss episodes (r = 0.300, p<0.05 and r = 0.322, p<0.05, respectively). Moreover, a positive correlation occurred between insulin, HOMA-IR, c-peptide and BMI (r = 0.436, p <0.05; r = 0.384, p<0.05 and r = 0.450, p<0.05, respectively). In conclusion, lipocalin-2 and insulin may serve as biomarkers for alopecia areata. Further studies are needed to evaluate the role of insulin as a prognostic factor in alopecia areata.

Lipocalin2 as a useful biomarker for risk stratification in patients with acute cholangitis: A single-center prospective and observational study.

BACKGROUND: Lipocalin2 (LCN2) is being increasingly used to diagnose and predict severe bacterial infection. We aimed to evaluate the predictive value of serum lipocalin 2 for severity grading of acute cholangitis (AC) on patient admission. METHODS: A total of 108 patients were enrolled in this study. Blood samples were obtained at admission. Receiver operating characteristic (ROC) curves were built to assess the abilities of LCN2 levels to predict moderate/severe (vs. mild) or severe (vs. mild/moderate) AC with traditional markers of inflammation such as white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR). The correlations among the key research indicators were determined using spearman's test. Multivariate analysis was conducted to identify the risk factors for severe AC. RESULTS: The levels of LCN2 on admission increased significantly with the severity of AC. By analysis of ROC curve of biomarkers for differentiating patients with moderate to severe AC (versus mild AC), the AUC for LCN2 (0.925) was significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 262.2 ng/mL, with a sensitivity of 90.8% and specificity of 81.4%. In addition, the AUC for LCN2 (0.912) for severe acute cholangitis was also significantly greater than that for other inflammatory markers, and the optimal cut-off value of LCN2 was 325.7 ng/mL. The sensitivity and specificity were 86.1% and 83.3%, respectively. Furthermore, LCN2 the closest relationships were found between LCN2 and PCT (r = 0.8054, P < 0.001) through Spearman's test. Multivariate analysis showed that LCN2 was the only risk factor predicting severe AC (P < 0.05). CONCLUSION: Serum LCN2 concentration on patient admission could better predict severe acute cholangitis than WBC, CRP, PCT and NLR. Serum LCN2 may become a potential biomarker in the risk stratification of acute cholangitis and in indicating the time of biliary drainage.

Association of plasma neutrophil gelatinase-associated lipocalin and thoracic aorta calcification in maintenance hemodialysis patients with and without diabetes.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a bone-derived factor involved in metabolism, but also a biomarker of kidney disease and cardiovascular pathophysiology. We conducted this cross-sectional observational study to explore relationships between plasma NGAL and thoracic aorta calcification (TAC) in maintenance hemodialysis (MHD) patients with and without diabetes. METHODS: Plasma NGAL was measured by ELISA, TAC was evaluated via computed tomography scan using a 3D quantification method or chest radiography aortic arch calcification score. Spearman correlation, Logistic regression and Partial correlation analysis were used to describe the correlations between NGAL and TAC. RESULTS: Plasma NGAL levels were lower in MHD patients with diabetes compared to those without diabetes (49.33(42.37, 55.48) vs 56.78(44.37, 674.13) ng/mL, P = 0.026). In MHD patients without diabetes, lg (NGAL) was positively correlated with ARC value(R = 0.612, P = 0.003) analyzed by Spearman correlation; for partial correlation analysis, lg (NGAL) was positively correlated with ARC value, after adjusting for age and sex (R = 0.550, P = 0.015), adjusting for age, sex and CHD (R = 0.565, P = 0.015), adjusting for age, sex, CHD and Alb (R = 0.536, P = 0.027), or adjusting for age, sex, CHD, Alb, and dialyzer membrane (polysulfone) (R = 0.590, P = 0.016); however, when adjusting for age, sex, CHD, Alb and Ca, the correlation between lg (NGAL) and ARC value disappeared. Positive correlation were found between NGAL and Ca (R = 0.644, P < 0.001), Ca and ACR (R = 0.534, P = 0.013) in Spearman coefficient analysis. CONCLUSION: There were positive correlations among plasma NGAL, serum Ca and ARC in MHD patients without diabetes; which suggests that NGAL is possibly a participant in cardiovascular calcification, in non-diabetic MHD.

Prognostic utility of neutrophil gelatinase associated lipocalin in cardiac ICU: A prospective study.

Our study aims to evaluate the role of neutrophil gelatinase associated lipocalin (NGAL) as an early surrogate marker in predicting acute kidney injury (AKI) and mortality in cardiac ICU patients. The study was conducted at SRN Hospital, excluding those with known renal diseases. Out of 152 patients, 56 developed AKI (cases) and 96 were our controls. Higher NGAL was associated with increased mortality rates (P = 0.0201 and 0.0255 for serum and urinary NGAL respectively). Our study concluded that NGAL measurement at admission may be a boon in improving the outcome of cardiac ICU patients.

Circulating Lipocalin-2 level is positively associated with cognitive impairment in patients with metabolic syndrome.

The association between Lipocalin-2 (LCN2) and cognition in patients with metabolic syndrome (MetS) has not been thoroughly investigated. We aimed to evaluate whether serum LCN2 levels are associated with the alteration of cognitive function in patients with MetS. The total of 191 non-demented participants with MetS were enrolled onto the study in 2015, and a cohort study was conducted in a subpopulation in 2020. After adjustment for sex, age, waist circumference, creatinine levels, and HbA1C, an association between the higher serum LCN2 levels and the lower Montreal cognitive assessment (MoCA) scores was observed (B = - 0.045; 95%CI - 0.087, - 0.004; p 0.030). A total of 30 participants were followed-up in 2020. Serum LCN2 levels were decreased in correlation with age (23.31 ± 12.32 ng/ml in 2015 and 15.98 ± 11.28 ng/ml in 2020, p 0.024), while other metabolic parameters were unchanged. Magnetic resonance imaging studies were conducted on a subsample of patients in 2020 (n = 15). Associations between high serum LCN2 levels from 2015 and 2020 and changes in brain volume of hippocampus and prefrontal cortex from 2020 have been observed. These findings suggest a relationship between changes of the level of circulating LCN2, cognitive impairment, and changes in brain volume in patients with MetS. However, further investigation is still needed to explore the direct effect of circulating LCN2 on the cognition of MetS patients.

Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients. METHODS: This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed. RESULTS: AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently. CONCLUSION: Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.

Identification of CCL20 and LCN2 as Efficient Serological Tools for Detection of Hepatocellular Carcinoma.

Objectives: To discover a more powerful diagnostic tool for the detection of hepatocellular carcinoma (HCC). Methods: 16 extracellularly located candidates were selected by analyzing the expression array datasets in GEO. 10 of them were validated in clinical samples by ELISA. Differences of each variable were compared by one-way ANOVA or Kruskal-Wallis test. CCL20 and LCN2 were determined in all samples (HCC, 167; liver cirrhosis, 106; and healthy control, 106) and finally chosen for the construction of the combination model by binary logistic regression. The models were first built using a comprehensive control, including both liver cirrhosis (LC) and healthy donors. Then, the models were rebuilt by using the LC group alone as a control. ROC analysis was performed to compare the diagnostic efficiency of each indicator. Results: Levels of CCL20 and LCN2 in HCC sera were significantly higher than those in all controls. Using the comprehensive control, ROC curves showed that the optimum diagnostic cutoff of the CCL20 and LCN2 combination was 0.443 (area under curve (AUC) of 0.927 (95% CI 0.896-0.951), sensitivity of 0.808, specificity of 0.892, and accuracy of 0.859). For detection of HCC from LC control, the optimum diagnostic cutoff was 0.590 (AUC of 0.919 (95% CI 0.880-0.948), sensitivity of 0.814, specificity of 0.868, and accuracy of 0.834). Furthermore, the model maintained diagnostic accuracy for patients with HCC in the early stage, with the sensitivity and specificity of 0.75 and 0.77 from LC control, yet the AFP only reached 0.5 and 0.67, respectively. Conclusion: A combination model composed of CCL20 and LCN2 may serve as a more efficient tool for distinguishing HCC from nonmalignant liver diseases.

Risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) in sepsis patients.

OBJECTIVE: Sepsis is a host response with life-threatening organ dysfunction caused by an infection. Although the overall mortality rate has increased from 30% to 37% by the surviving sepsis campaign, it is still not acceptable. Early identification, accurate stratification and appropriate intervention can improve the prognosis. In this study we assessed the risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) as a biomarker in sepsis patients. METHODS: A total of 112 sepsis patients (38 patients with sepsis, 41 patients with severe sepsis, 33 patients with septic shock) and 25 healthy controls were enrolled in this study. Serum samples of all patients were collected and frozen before testing. Basic patient information was collected, including age, gender, primary infection, complications, and so on. Results of serum calcitonin, lactic acid, and SOFA score were followed up for 28 days. RESULTS: Levels of serum procalcitonin (PCT), serum lactate, Sequential Organ Failure Assessment (SOFA) score and sNGAL of sepsis patients were significantly higher (p<0.05) than those of controls. The sNGAL level in sepsis patients who were alive on the 28th day of follow-up was significantly lower (p<0.05) than that of sepsis patients who had died before the 28th day of follow-up. Multiple logistic regression analysis showed that sNGAL-0h and lactates were independent risk factors of death due to sepsis within 28 days. At cut-off value of 250 ng/mL, the sensitivity and specificity sNGAL-0h predicting the 28-day mortality in septic patients were 0.838 and 0.827, respectively. The sNGAL level in sepsis patients with acute kidney injury (AKI) was significantly higher (p<0.05) than in sepsis patients without AKI. CONCLUSION: Serum NGAL may contribute to the assessment of the severity of sepsis. Serum NGAL and lactate can be independent risk factors for 28-day mortality in sepsis patients. Serum NGAL has potential of predicting septic-AKI.

Association of significantly elevated plasma levels of NGAL and IGFBP4 in patients with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a type of progressive kidney disease affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine (sCr) levels. However, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required for early diagnosis to effectively manage DN progression. METHODS: In this study, a cohort of 159 individuals were clinically evaluated and the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 were determined using Multiplexing Assays. Additionally, the association between the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN were compared to those in patients with T2D without kidney disease and control participants. RESULTS: Circulating level of NGAL were significantly higher in people with DN compared to people with T2D and non-diabetic groups (92.76 ± 7.5, 57.22 ± 8.7, and 52.47 ± 2.9 mg/L, respectively; p <  0.0001). IGFBP-4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to T2D and non-diabetic people (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8 respectively, ANOVA p <  0.01). The data from this study shows a significant positive correlation between NGAL and IGFBP-4 in people with DN (ρ = .620, p <  0.005). IGFBP-4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. CONCLUSION: The data from this study shows a parallel increase in the plasma levels of NGAL and IGFBP-4 in DN. This highlights the potential to use these markers for early diagnosis of DN.

Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers.

BACKGROUND: Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer's disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer's disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer's disease, differential diagnoses, other biomarkers, and clinical data. METHODS: For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer's disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer's disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). RESULTS: Plasma Lipocalin-2 was significantly lower in Alzheimer's disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer's pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer's disease and healthy controls were 0.783 (95%CI: 0.712-0.855) in the study cohort and 0.766 (95%CI: 0.627-0.905) in the validation cohort. The area under the curve for Alzheimer's disease versus vascular dementia was 0.778 (95%CI: 0.667-0.890) in the study cohort. In Alzheimer's disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer's disease (p = 0.013). CONCLUSIONS: Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer's disease and seems to be independent from currently employed biomarkers.

Serum levels of lipocalin-2 are elevated at early times in African American relapsing remitting multiple sclerosis patients.

Previous studies showed that depleting Liver Kinase-B1 (LKB1) from astrocytes increased inflammatory factors lipocalin-2 (LCN2) and osteopontin (OPN) in EAE. A single nucleotide polymorphism (SNP) in STK11 (encoding LKB1) is a risk factor for MS, suggesting increased LCN2 or OPN contributes to risk. Serum LCN2 and OPN levels in African American female MS patients were higher than healthy controls, and while levels increased with disease duration in cases without the SNP, levels decreased with duration in cases with the SNP. Increased MS risk associated with the STK11 SNP may be due to higher LCN2 or OPN levels at early times.