Role of Urinary Biomarkers (Transforming Growth Factor ß1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve.

Background: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-ß1 (TGF-ß1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. Aim: To compare the urinary levels of TGF-ß1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. Materials and Methods: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-ß1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Results: Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-ß1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 µg/ml, 0.439 µg/ml, and 0.382 µg/ml) than the control group (0.243 µg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-ß1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 µg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). Conclusion: The elevated uTGF-ß1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis.

Introduction: Early and accurate diagnosis of urinary tract infection (UTI) can prevent serious sequelae including chronic kidney disease. Multiple individual studies have identified urine neutrophil gelatinase-associated lipocalin (uNGAL) as a promising biomarker for early diagnosis of UTI. We sought to understand the distribution and diagnostic accuracy of uNGAL values in patients presenting with UTI symptoms. Methods: Our systematic literature reviews in PubMed, Embase, and Cochrane Reviews up to March 2024, identified 25 studies reporting mean/median, standard deviation/quartiles, and detection limits of uNGAL in symptomatic patients with and without culture-confirmed UTI. Seventeen studies were in children. Meta-analyses were performed using the quantile estimation (QE) method estimating the distributions of uNGAL, which were then compared between the UTI and non-UTI groups for identifying the best cut-off points maximizing the Youden index. Sensitivity analyses were performed on all 25 studies including adult patients. Results: We found that uNGAL levels were significantly higher in samples with confirmed UTI compared to those without. In pediatric studies, median and 95% confidence interval (CI) of uNGAL values were 22.41 (95% CI of 9.94, 50.54) ng/mL in non-UTI group vs. 118.85 (95% CI of 43.07, 327.97) ng/mL in UTI group. We estimated the cut-off point of 48.43 ng/mL with highest sensitivity (96%) and specificity (97%) in children. Sensitivity analysis including both pediatric and adult studies yielded similar results. Discussion: The level of uNGAL in symptomatic patients with confirmed UTI is much higher than that reported in patients without UTI. It may be used as a diagnostic tool to identify UTI early among symptomatic patients. The range of uNGAL concentrations and cut-off points reported in subjects with UTI is much lower than that reported in patients with acute intrinsic kidney injury. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023370451).

Is the urinary neutrophil gelatinase-associated lipocalin concentration in children and adolescents with type 1 diabetes mellitus different from that in healthy children?

Introduction: Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies. Materials and methods: In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age. Results: There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL vs 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg vs 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL. Conclusions: We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.

Emerging insights into Lipocalin-2: Unraveling its role in Parkinson's Disease.

Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder globally, marked by a complex pathogenesis. Lipocalin-2 (LCN2) emerges as a crucial factor during the progression of PD. Belonging to the lipocalin family, LCN2 is integral to several biological functions, including glial cell activation, iron homeostasis regulation, immune response, inflammatory reactions, and oxidative stress mitigation. Substantial research has highlighted marked increases in LCN2 expression within the substantia nigra (SN), cerebrospinal fluid (CSF), and blood of individuals with PD. This review focuses on the pathological roles of LCN2 in neuroinflammation, aging, neuronal damage, and iron dysregulation in PD. It aims to explore the underlying mechanisms of LCN2 in the disease and potential therapeutic targets that could inform future treatment strategies.

Trajectory pattern of serially measured acute kidney injury biomarkers in critically ill patients: a prospective observational study.

BACKGROUND: The clinical value of the trajectory of temporal changes in acute kidney injury (AKI) biomarkers has not been well established among intensive care unit (ICU) patients. METHODS: This is a single-center, prospective observational study, performed at a mixed ICU in a teaching medical institute in Tokyo, Japan. Adult ICU patients with an arterial line and urethral catheter were enrolled from September 2014 to March 2015. Patients who stayed in the ICU for less than 48 h and patients with known end-stage renal disease were excluded from the study. Blood and urine samples were collected for measurement of AKI biomarkers at 0, 12, 24, and 48 h after ICU admission. The primary outcome was major adverse kidney events (MAKE) at discharge, defined as a composite of death, dialysis dependency, and persistent loss of kidney function (≥ 25% decline in eGFR). RESULTS: The study included 156 patients. Serum creatinine-based estimated glomerular filtration rate (eGFR), plasma neutrophil gelatinase-associated lipocalin (NGAL), and urinary liver-type fatty acid-binding protein (uL-FABP) were serially measured and each variable was classified into three groups based on group-based trajectory modeling analysis. While the trajectory curves moved parallel to each other (i.e., "low," "middle," and "high") for eGFR and plasma NGAL, the uL-FABP curves showed distinct trajectory patterns and moved in different directions ("low and constant," "high and exponential decrease," and "high and exponential increase"). These trajectory patterns were significantly associated with MAKE. MAKE occurred in 16 (18%), 16 (40%), and 9 (100%) patients in the "low and constant," "high and exponential decrease," and "high and exponential increase" groups, respectively, based on uL-FABP levels (p-value < 0.001). The initial value and the 12-h change in uL-FABP were both significantly associated with MAKE, even after adjusting for eGFR [Odds ratio (95% confidence interval): 1.45 (1.17-1.83) and 1.43 (1.12-1.88) for increase of initial value and 12-h change of log-transformed uL-FABP by 1 point, respectively]. CONCLUSIONS: Trajectory pattern of serially measured urinary L-FABP was significantly associated with MAKE in ICU patients.

The predictive role of neutrophil gelatinase-associated lipocalin in coronary artery disease.

The prognosis holds significant implications for the long-term quality of life among patients suffering from coronary artery disease. However, a pressing challenge lies in the absence of reliable biomarkers that can establish a definitive correlation between these biomarkers and the prognosis of coronary artery heart disease. This review paper delves into the critical role of neutrophil gelatinase-associated lipocalin (NGAL) in predicting outcomes in coronary artery disease. It examines the influence of NGAL on various clinical manifestations, including stable angina, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and isolated coronary artery dilation. Furthermore, this review provides recommendations aimed at enhancing the rigor and impact of future research, thereby serving as a valuable reference for subsequent studies in this domain.

Bioinformatics and experimental approach identify lipocalin 2 as a diagnostic and prognostic indicator for lung adenocarcinoma.

BACKGROUND: lipocalin 2 (LCN2) is a secreted glycoprotein that plays key roles in tumorigenesis and progression. Interestingly, LCN2 appears to have a contradictory function in developing lung adenocarcinoma (LUAD). Thus, we intend to explore the role of LCN2 in LUAD through bioinformatics and experimental validation. METHODS: LCN2 expression of LUAD was investigated in the TCGA, TIMER and HPA databases. The relationship between LCN2 and prognosis was investigated by KM plotter, TCGA and GEO databases. GO, KEGG and protein-protein interactions network analysis were conducted to investigate the potential mechanism of LCN2. The relevance of LCN2 to cancer-immune infiltrates was investigated in the TCGA and TIMER databases. Quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay were performed to identify the expression level of LCN2 in cells and serum samples. The CCK-8, wound healing and transwell assay were used to confirm the effect of LCN2 on cell proliferation, migration and invasion in LUAD. The receiver operating characteristic curve was utilized to assess the diagnostic efficiency of LCN2 further. RESULTS: LCN2 expression was significantly upregulated in LUAD (P < 0.05), and was correlated with the clinical stage, tumor size, lymph node metastasis and distant metastasis (P < 0.05). There was a high correlation between high LCN2 and worse prognosis in LUAD. Functional network analysis suggested that LCN2 was associated with multiple signal pathways in cancers, such as JAK-STAT, TNF, NF-κB, HIF-1 and PI3K-Akt signal pathways. In addition, the knockdown of LCN2 significantly inhibited the ability of cell proliferation, migration and invasion. Immune infiltration analysis indicated that LCN2 is associated with multiple immune cell infiltration. Notably, LCN2 demonstrated high diagnostic efficiency for LUAD (AUC = 0.818, P < 0.05), especially for stage III-IV patients could reach 0.895. CONCLUSIONS: LCN2 as an oncogenic glycoprotein promotes the cancer progression related to immune infiltrates, which might be a potential diagnostic and prognostic marker in LUAD.

Evaluation of urinary neutrophil gelatinase associated lipocalin in the early diagnosis of acute kidney injury with sepsis.

BACKGROUND: To assess the utility of urinary neutrophil gelatinase associated lipocalin (uNGAL) in the diagnosis of acute kidney injury (AKI) in the context of sepsis. METHODS: In this retrospective study, a total of 142 patients with sepsis treated in the Third Hospital of Shanxi Medical University from January 2019 to January 2021 were included. Patients diagnosed with AKI complicated with sepsis were categorized into the AKI group (n=70 cases), and patients diagnosed with sepsis were classified into the non-AKI group (n=72 cases). We collected and analyzed data on serum creatinine (Scr) and uNGAL levels. The ROC (receivers operating characteristics) curve was used to evaluate the sensitivity and specificity of uNGAL in the diagnosis of AKI with sepsis. RESULTS: The level of uNGAL in the AKI group increased over time following admission, which was not observed in the non-AKI group. Twenty-four hours after admission, the level of uNGAL in the AKI group was significantly higher than that in the non-AKI group (P < 0.05), but there was no significant difference in Scr level between the two groups (P > 0.05). At 72 hours after admission, the AUC of uNGAL in predicting AKI was 0.989 (95% CI: 1.018-1.085), and its intercept value was 961.3 ng/ml. At the same time, the correlation analysis showed that the level of uNGAL was positively correlated with the occurrence of AKI. CONCLUSION: uNGAL is superior to Scr for early diagnosis of AKI patients with sepsis.

Plasma proenkephalin and neutrophil gelatinase-associated lipocalin predict mortality in ICU patients with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients admitted to intensive care unit (ICU) and mortality rates for this condition are high. To reduce the high incidence of short-term mortality, reliable prognostic indicators are required to facilitate early diagnosis and treatment of AKI. We assessed the ability of plasma proenkephalin (p­PENK) and plasma neutrophil gelatinase-associated lipocalin (p­NGAL) to predict 28-day mortality in AKI patients in intensive care. METHODS: This prospective study, carried out between January 2019 and December 2019, comprised 150 patients (100 male) diagnosed with AKI after excluding 20 patients discharged within 24 h and those with missing hospitalization data. Blood samples were collected to determine admission p-PENK and p-NGAL levels. The study outcome was 28­day mortality. RESULTS: The mean patient age was 68 years (female, 33%). The average P­PENK and p­NGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. P­PENK levels >0.36 ng/µL and p­NGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28­day mortality for patients with AKI (adjusted hazard ratios 0.785 [95% confidence interval 0.706-0.865, P<0.001] and 0.700 [95% confidence interval 0.611-0.789, P<0.001], respectively). This association was significant for mortality in patients in intensive care with AKI. Baseline p-PENK (0.36 ng/µL) and p-NGAL (230.30 ng/mL) levels and their respective cut-off values showed clinical value in predicting 28-day mortality. CONCLUSION: Serum PENK and NGAL levels, when used in conjunction, improved the accuracy of predicting 28-day mortality in patients with AKI while retaining sensitivity and specificity.

The use of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for diagnosis of hepato-renal syndrome in advanced cirrhotic patients.

BACKGROUND: Chronic liver disease is a common and important clinical problem.Hepatorenal syndrome (HRS) is a life threatening complication. Serum creatinine (Cr) remains the only conventional indicator of renal function. However, the interpretation of serum Cr level can be confounded by malnutrition and reduced muscle mass often observed in patients with severe liver disease. Here, we present a cross-sectional study to explore the sensitivity and specificity of other markers as urinary KIM-1 and NGAL for cases of HRS. METHODS: Cross-sectional study was conducted on 88 patients who were admitted to Alexandria main university hospital. Enrolled patients were divided in two groups; group 1: patients with advanced liver cirrhosis (child B and C) who have normal kidney functions while group 2: patients who developed HRS. Stata© version 14.2 software package was used for analysis. RESULTS: Group 1 included 18 males and 26 females compared to 25 males and 19 females in group 2 (p = 0.135). Only the urinary KIM-1 showed a statistically significant difference between both groups in the multivariate logistic regression analysis adjusted for gender, serum bilirubin, serum albumin, INR, serum K, AST and ALT levels. CONCLUSION: In conclusion, our study aligns with prior research, as seen in the consistent findings regarding Urinary NGAL elevation in cirrhotic patients with AKI. Urinary KIM-1, independent of Urinary NGAL, may have a role in precisely distinguishing between advanced liver cirrhosis and HRS and merits further exploration.

The utility of serum neutrophil gelatinase-associated lipocalin level on predicting autosomal dominant polycystic kidney disease progression.

INTRODUCTION: We focused on neutrophil gelatinase-associated lipocalin (NGAL) and autosomal dominant polycystic kidney disease (ADPKD) progression. METHODS: ADPKD patients with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 were included. Serum NGAL level and NGAL to eGFR ratio (NGR), height-adjusted total kidney volume (hTKV) were assessed initially. Patients were followed-up for 5 years. RESULTS: Sixty one patients were enrolled and initial eGFR was 73.6 (48.9-101.5) ml/min/1.73m2. EGFR declined by 3.7 mL/min/1.73m2 per year. Thirty four patients (55.7%) exhibited rapid progression. Rapid progression group had lower serum NGAL levels (p < 0.001) and higher hTKV (p < 0.001). Lower serum NGAL level was a risk factor for rapid progression (p < 0.001). NGR was not associated with rapid progression. Serum NGAL level was predictive in for rapid progression ROC analysis (cut-off <10.62 ng/mL). CONCLUSION: Relatively lower serum NGAL levels can predict worse outcomes in ADPKD and can provide risk stratification in patients with ADPKD.

The Role of Biomarkers in Diagnosis of Sepsis and Acute Kidney Injury.

Sepsis and acute kidney injury (AKI) are two major public health concerns that contribute significantly to illness and death worldwide. Early diagnosis and prompt treatment are essential for achieving the best possible outcomes. To date, there are no specific clinical, imaging, or biochemical indicators available to diagnose sepsis, and diagnosis of AKI based on the KDIGO criterion has limitations. To improve the diagnostic process for sepsis and AKI, it is essential to continually evolve our understanding of these conditions. Delays in diagnosis and appropriate treatment can have serious consequences. Sepsis and AKI often occur together, and patients with kidney dysfunction are more prone to developing sepsis. Therefore, identifying potential biomarkers for both conditions is crucial. In this review, we talk about the main biomarkers that evolve the diagnostic of sepsis and AKI, namely neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and cell-free DNA.

The Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplants.

Tacrolimus (TAC) has a narrow therapeutic window and patient-specific pharmacokinetic variability. In our study, we analyzed the association between TAC exposure, metabolism, and kidney graft outcomes (function, rejection, and histological lesions). TAC trough (C0), coefficient of variation (TAC CV), concentration/dose ratio (C/D), and biomarkers related to kidney injury molecule-1 (KIM-1) and neutrophil gelatinase lipocalin (NGAL) were analyzed. We examined 174 patients who were subjected to a triple immunosuppressive regimen and underwent kidney transplantation between 2017 and 2022. Surveillance biopsies were performed at the time of kidney implantation and at three and twelve months after transplantation. We classified patients based on their Tac C/D ratios, classifying them as fast (C/D ratio < 1.05 ng/mL × 1/mg) or slow (C/D ratio ≥ 1.05 ng/mL × 1/mg) metabolizers. TAC exposure/metabolism did not significantly correlate with interstitial fibrosis/tubular atrophy (IF/TA) progression during the first year after kidney transplantation. TAC CV third tertile was associated with a higher chronicity score at one-year biopsy. TAC C/D ratio at three months and Tac C0 at six months were associated with rejection during the first year after transplantation. A fast TAC metabolism at six months was associated with reduced kidney graft function one year (OR: 2.141, 95% CI: 1.044-4.389, p = 0.038) and two years after transplantation (OR: 4.654, 95% CI: 1.197-18.097, p = 0.026), and TAC CV was associated with reduced eGFR at three years. uNGAL correlated with IF/TA and chronicity scores at three months and negatively correlated with TAC C0 and C/D at three months and one year. Conclusion: Calculating the C/D ratio at three and six months after transplantation may help to identify patients at risk of suffering acute rejection and deterioration of graft function.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia.

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

Comparison of Urinary Biomarkers in Diagnosis of Ureteropelvic Junction Obstruction and Differentiation from Nonobstructive Dilatation.

Background and Aims: Differentiation of nonobstructive dilatation (NOD) from ureteropelvic junction obstruction (UPJO) is a challenge in children with antenatally detected hydronephrosis. The aim of this study is to compare the utility of urinary biomarkers: carbohydrate antigen (CA 19-9), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM) in diagnosing UPJO. Methods: A prospective study was conducted after obtaining ethical clearance between 2021 and 2022. Group 1 - control group (n = 30): children with normal antenatal ultrasound with no urinary symptoms. Group 2 - study group (n = 48): children with unilateral hydronephrosis: Group 2a - NOD (n = 24): children stable on ultrasound and diuretic renogram and Group 2b - UPJO (n = 24): children who worsened to Grade 4 hydronephrosis on ultrasound/worsening of differential renal function (10% drop) on renogram who underwent pyeloplasty. Urinary biomarkers NGAL, KIM-1, and CA 19-9 were measured using the enzyme-linked immune absorbent assay method. Results: The urine CA 19-9 level was 128.05 ± 4.08 U/mL in the UPJO group, and this was significantly higher (P = 0.001) than NOD, 70.29 ± 4.41, and controls, 1.91 ± 1.57. The urine NGAL level was 21.41 ± 4.44 pg/mL in UPJO, and this was significantly higher than controls, 2.669 ± 0.513, but not NOD, 24.55 ± 2.67. The urine KIM level was 817 ± 15.84 pg/mL in the UPJO group, and this was significantly higher than controls, 285 ± 8.10, but not NOD, 768.23 ± 15.12. Receiver operating characteristic analysis of CA 19-9 revealed a urine biomarker cutoff of 95 U/mL for diagnosing UPJO (sensitivity 95%; specificity 96%; and area under the curve 0.99). Conclusions: CA 19-9 is a superior marker compared to NGAL and KIM in differentiating UPJO from NOD. Further studies with larger numbers are warranted.

Clinical Impacts of Urinary Neutrophil Gelatinase-Associated Lipocalin in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for renal injury. However, the association between urinary NGAL concentrations and renal and cardiovascular events in patients with CKD undergoing PCI has not been elucidated. This study investigated the clinical impact of urinary NGAL concentrations on renal and cardiovascular outcomes in patients with non-dialysis CKD undergoing PCI.Methods and Results: We enrolled 124 patients with non-dialysis CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective PCI. Patients were divided into low and high NGAL groups based on the median urinary NGAL concentration measured the day before PCI. Patients were monitored for renal and cardiovascular events during the 2-year follow-up period. Kaplan-Meier analyses showed that the incidence of renal and cardiovascular events was higher in the high than low NGAL group (log-rank P<0.001 and P=0.032, respectively). Multivariate Cox proportional hazards analyses revealed that urinary NGAL was an independent risk factor for renal (hazard ratio [HR] 4.790; 95% confidence interval [CI] 1.537-14.924; P=0.007) and cardiovascular (HR 2.938; 95% CI 1.034-8.347; P=0.043) events. CONCLUSIONS: Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

Disposable label-free electrochemical immunosensor based on gold nanoparticles-Prussian blue for neutrophil gelatinase-associated lipocalin detection in urine samples.

Neutrophil gelatinase-associated lipocalin (NGAL) is a remarkable biomarker for assessing acute kidney injury. In this study, we developed a novel label-free NGAL electrochemical immunosensor based on gold nanoparticles (AuNPs) and Prussian blue (PB) without an external mediator. The AuNPs-PB based immunosensor was fabricated on a custom gold-electrode (AuE)-based polypropylene (PP) substrate. We systematically assessed and optimized key experimental parameters, including the process of AuNPs-PB electrodeposition, antibody concentration, and incubation time. The immunosensor response toward NGAL was determined using differential pulse voltammetry, where the decrease in the oxidation current response of the PB redox probe correlating with the increase in NGAL concentration. Our results demonstrated that the synergistic benefits of both AuNPs and PB significantly improved electrochemical activity for NGAL detection and provided a highly stable sensor across a range of pH values. The label-free immunosensor exhibited two linear ranges: 0.10-1.40 ng mL-1 and 1.40-25.0 ng mL-1, with a low detection limit of 0.094 ng mL-1. The developed NGAL immunosensor displayed high selectivity and excellent reproducibility. Furthermore, NGAL detection was completed within 30 min and the immunosensor exhibited storage stability for six weeks. Notably, NGAL levels determined in human urine samples using this developed label-free immunosensor showed good agreement with the results obtained from the enzyme-linked immunosorbent assay. This novel label-free NGAL immunosensor provides great potential in developing NGAL point-of-care testing applications.

Value of serum iron and urine neutrophil gelatinase-associated lipocalin in predicting the mortality of critically ill patients with sepsis.

INTRODUCTION: We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis. METHODS: Serum or urine concentrations of iron metabolism-related parameters on intensive care unit admission were measured in a prospective cohort of 133 eligible patients with sepsis according to the Sepsis-3 criteria, and these values were compared between survivors and nonsurvivors, categorized according to their 60-day survival status. Cox regression analyses were performed to examine the association between iron parameters and 60-day mortality. Kaplan-Meier methods were used to illustrate the differences in survival between different iron parameters. RESULTS: Of the 133 patients included in the study, 61 (45.8%) had died by day 60. After adjusting for confounding variables, higher concentrations of serum iron (cut-off 9.5 µmol/mL) and higher concentrations of urine neutrophil gelatinase-associated lipocalin (uNGAL; cut-off 169.3 ng/mL) were associated with a significantly greater risk of death in the Cox regression analysis. These two biomarkers combined with Sequential Organ Failure Assessment (SOFA) scores increased the area under the receiver operating characteristic (AUROC) curve to 0.85. DISCUSSION: These findings suggest that higher concentrations of serum iron and uNGAL are each associated with higher 60-day mortality, and they add significant accuracy to this prediction in combination with SOFA. Abbreviations: uNGAL: urine neutrophil gelatinase-associated lipocalin; ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment; APACHE II: the Acute Physiology and Chronic Health Evaluation II; ELISA: enzyme-linked immunosorbent assay; HR: hazard ratio; CIs: confidence intervals; WBC: white blood cell; TBIL: total bilirubin.

Neutrophil Gelatinase-Associated Lipocalin for the Differentiation of Mucinous Pancreatic Cystic Lesions.

Undetermined pancreatic cystic lesion (PCL) differentiation benefits from endoscopic ultrasound (EUS) based on morphology and cyst fluid analysis, but room for new biomarkers exists. Our aim was to assess the intracystic and serum diagnostic value of neutrophil gelatinase-associated lipocalin (Ngal) and interleukin 1 beta (IL-1ß) for differentiation of PCLs. This prospective study included patients from one tertiary hospital, evaluated between April 2018 and May 2020. EUS fine-needle aspiration or pancreatic pseudocysts drainage was the source of PCL intracystic liquid. The final diagnosis was based on surgery or EUS results (morphology, cytology, glucose, and CEA-carcinoembryogenic antigen). The intracystic samples were tested for Ngal, IL-1ß, glucose, and CEA, and serum for Ngal and IL-1ß. We evaluated 63 cysts, 33 pseudocysts, and 30 non-inflammatory cysts. The diagnostic sensitivity and specificity for mucinous PCL was 70.8% and 92.3% for intracystic Ngal (cut-off: 500-800 ng/dL), without correlation with serum Ngal, no matter the inclusion of infected pseudocysts. After exclusion of infected pseudocysts, the sensitivity and specificity for glucose were 87% and 75%, respectively, and for CEA, they were 87.1%, and 96.8%, respectively. Intracystic Ngal shows promise in differentiating mucinous PCLs, but researchers need to conduct further studies to confirm its effectiveness. Intracystic IL-1ß and serum Ngal made no diagnostic contribution.

Prognostic Biomarkers and AKI: Potential to Enhance the Identification of Post-Operative Patients at Risk of Loss of Renal Function.

Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit. The conventional markers of AKI, namely serum creatinine and urine output are the mainstay of defining chronic kidney disease but are less suited to the acute phase. Such concerns are compounded in surgical patients given they often have significantly reduced mobility, suboptimal levels of nutrition and reduced muscle bulk. Many patients may also have misleadingly low serum creatinine and high urine output due to aggressive fluid resuscitation, particularly in intensive care units. Over the last two decades, considerable information has accrued with regard to the performance of what was termed "novel" biomarkers of AKI, and here, we discuss the most examined molecules and performance in surgical settings. We also discuss the application of biomarkers to guide patients' postoperative care.

Kidney damage is common after major surgery with a recent study showing almost 1 in 5 patients suffer kidney damage. The usual tests for measuring kidney function are excellent in the outpatient but not so good in acute scenario's. Therefore, there has been a lot of interest in new markers of kidney damage (so-called novel biomarkers) which perform well acutely and allow earlier detection of damage allowing treatment to be started earlier. This article summarises the currently available biomarkers for use post-operatively and points out the different information that can be achieved by using them routinely.