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Objectives This study was aimed to investigate the diagnostic values of serum levels of asprosin and neutrophil gelatinase-associated lipocalin (NGAL) in Retinopathy of prematurity (ROP) and to assess the role of these biomarkers on the development and progression of the condition. Methods This study was carried out from April 2020 to February 2021 in the department of ophthalmology of a tertiary hospital in Turkey. Thirty patients diagnosed with ROP and 30 healthy newborns were included the study. Serum NGAL and asprosin levels were determined via ELISA. Results The median serum NGAL levels were found to be similar between the ROP group and the control group (p=0.595). Median asprosin levels were significantly higher in patients diagnosed with ROP [46.58 (12.70–142.28) ng/mL] compared to healthy subjects [13.05 (10.92–17.73) ng/mL] (p=0.001). The optimal cut-off value of asprosin by ROC analysis was 30 ng/mL (AUC: 0.754, p=0.001) for diagnosing ROP. Serum asprosin levels were positively correlated with serum ALP levels and inversely correlated with gestational week, uric acid and AST values (all, p Conclusions Our results demonstrated that asprosin, but not NGAL, could be a biomarker for the diagnosis of ROP.

Aim: We explored the concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL) in healthy adults in the Jiangsu region in Eastern China and established a reference interval using latex-enhanced immunoturbidimetry to provide important guidelines for the interpretation and application of urinary NGAL in clinical practice. Methods: In total, 1970 eligible subjects from four regions were included in this study. The urinary NGAL levels were measured using an AU5800 automatic biochemical analyzer with its matched reagents. The urinary NGAL reference interval was established using the one-sided percentile method (95th percentile). Results: The urinary NGAL data were non-normally distributed. The urinary NGAL levels were not significantly different by sex or age. Therefore, the urinary NGAL reference interval in healthy adults in the Jiangsu region in Eastern China was

Purpose: To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis. Methods: A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI. Results: The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p

BACKGROUND: Insecticide usage has increased in the tropics and subtropics due to the high prevalence of vector-borne infections, even though insecticide use effectively reduces insect-borne diseases. Insecticide exposure can cause oxidative stress and have severe consequences for human health. The study was then designed to evaluate oxidative stress and its effects on immunomodulatory and renal integrity among Wistar rats exposed to pyrethroids. METHODS: Eighty-four Wistar rats were randomly selected and divided into two groups. Fifty-one rats were exposed to 1.2 %w/v pyrethroids, while the remaining thirty-three rats were grouped as non-exposed. The groups were divided into three different groups, each with 7, 21, and 41 days. After days of exposure, the animals in each group were anesthetized, and blood samples were collected from the inferior vena cava. Using standard spectrophotometric techniques, the levels of total antioxidant status (TAS), malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), urea, creatinine and uric acid were determined. Blood activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were determined. ELISA was used to determine levels of IgG, IgA, IgE, TNF-α, and NGAL. Data obtained were statistically compared. RESULTS: The serum mean levels of SOD, GPx, CAT, GSH, and TAS were significantly reduced (p

Coronary heart disease (CHD) has become the primary cause of death worldwide in both developed and developing countries.1 In China, the mortality rates of CHD in urban and rural residents were 122.04/100,000 and 115.32/100,000, respectively, in 2017.2 The Global Burden of Disease study reported that ischemic heart disease led to approximately 1.7 million deaths in China in 2016.3 CHD has become the leading cause of death in the Chinese population and a serious public health problem. In particular, acute coronary syndrome (ACS) is the chief and serious type of CHD, leading to ventricular remodeling and heart failure.4 Previous studies have also found that patients with ACS have a higher incidence of renal dysfunction.5,6 In recent years, the concept of cardiorenal syndrome (CRS) has been widely recognized, including a series of diseases involving the heart and kidney.7,8 Acute or chronic dysfunction of the heart or kidney may lead to acute or chronic dysfunction of another organ. In 2019, the American Heart Association issued a scientific statement on the classification, pathophysiology, diagnosis, and treatment strategy of CRS, which was divided into 5 subtypes.8 This is very important for the prognosis of patients with type 1 CRS by early detection and the treatment of renal dysfunction in patients with ACS. However, traditional laboratory indicators for kidney function, such as blood urea nitrogen and creatinine, are limited in the early diagnosis of acute kidney injury (AKI) because of their low sensitivity and specificity.9 In addition, diuretic treatment for acute heart failure (AHF) makes the evaluation of renal function more complicated. Recent studies have revealed that markers targeted for renal tubular injury have better early evaluation significance for patients with AKI, especially for patients with AHF, than traditional laboratory indicators. Among them, neutrophil gelatinase–associated lipocalin [neutrophil gelatinase–associated lipocalin (NGAL)], urinary kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are increased in the early stage in patients with AKI and can be used as biological markers of early renal dysfunction.10,11 However, the role of these renal tubular injury markers in type 1 CRS has not been clearly studied. Nicorandil can significantly alleviate the occurrence of angina pectoris,12 reduce the incidence of cardiovascular events, and improve the prognosis in patients with ACS. In patients with heart failure, nicorandil could reduce all-cause mortality, increase cardiac pump function,13 and improve left ventricular diastolic function.14 These protective effects of nicorandil might result from the dual vasodilation of coronary and peripheral arteries to increase coronary blood flow, reduce preload and afterload, and alleviate myocardial injury and cardiac remodeling.15 In addition, some studies have found that nicorandil can provide additional renal protection for chronic kidney disease or significantly reduce the incidence of contrast-induced nephropathy in patients undergoing coronary angiography or percutaneous coronary intervention.16 The possible mechanism of nicorandil is the reduction of vascular and renal dysfunction17 or the neutralization of nephrotoxicity by normalizing the TLR4/MAPK P38/NFκ-B inflammatory cascade.18 Moreover, oral nicorandil reduced cardiac death in hemodialysis patients undergoing coronary revascularization.19 Therefore, it is very interesting to study the effect of nicorandil on renal function in patients with type 1 CRS. This study will explore the effect of nicorandil on cardiac and renal function in Chinese patients with type I CRS caused by ACS.

The objective of the work was to determine diagnostic and predictive value of urinary neutrophil gelatinase-associated lipocalin in case of acute kidney injury in full-term infants with signs of severe perinatal pathology. A comprehensive clinical and paraclinical examination has been carried out in 95 newborns, of whom 65 infants had disorders of the functional renal state, and 30 children were diagnosed with acute kidney injury. A high sensitivity (100 %) and specificity (91.4 %) of neutrophil gelatinase-associated lipocalin has been found in urine during diagnostics of acute kidney injury in critically ill full-term newborns. High diagnostic value of this index is proved by diagnostic accuracy (94.7 %) and high AUROC index (0.97); high predictive value — by high parameters of a positive predictive value (88.0 %) and negative predictive value (100.0 %). A threshold level of urinary neutrophil gelatinase-associated lipocalin was detected to be higher than 589 mcg/g of creatinine that is indicative of the formation of acute kidney injury in full-term newborns with severe perinatal pathology. Considering a high predictive and diagnostic value, the authors recommend to apply this method of identification of acute kidney injury in the practical work of neonatal intensive care units.

Chronic kidney disease is a rare disease in horses, unlike humans and companion animals where it is frequently encountered. There are multiple causes, although, since the disease typically presents late in the disease process, the instigating factor is often not ascertained. Clinical signs most commonly include weight loss, ventral oedema and polyuria-polydipsia. There is a need for more sensitive markers of renal damage or dysfunction so that the disease can be detected earlier in its course. Serum symmetric dimethylarginine and neutrophil gelatinase-associated lipocalin are potential biomarkers that are being investigated in this regard. Currently, once the diagnosis has been made, treatment is supportive only, with no options to halt the progression of the disease. Although this is a terminal condition, horses can be maintained with an adequate quality of life for several years after diagnosis in some cases.

Background We investigated the predictive value of 11 serum biomarkers for renal and mortality end points in people with CKD. Methods Adults with CKD (n=139) were enrolled from outpatient clinics between February 2014 and November 2016. Biomarker quantification was performed using two multiplex arrays on a clinical-grade analyzer. Relationships between biomarkers and renal and mortality end points were investigated by random forests and Cox proportional hazards regression. Results The cohort was 56% male. The mean age was 63 years and median (IQR) CKD-EPI eGFR was 33 (24–51) ml/min per BSA. A total of 56 (40%) people developed a composite end point defined as ≥40% decline in eGFR, doubling of serum creatinine, RRT, or death over median (IQR) follow-up of 5.4 (4.7–5.7) years. Prediction of the composite end point was better with random forests trained on serum biomarkers compared with clinical variables (area under the curve of 0.81 versus 0.78). The predictive performance of biomarkers was further enhanced when considered alongside clinical variables (area under the curve of 0.83 versus 0.81 for biomarkers alone). Patients (n=27, 19%) with high soluble TNF receptor-1 (≥3 ng/ml) and neutrophil gelatinase-associated lipocalin (≥156 ng/ml), coupled with low complement 3a des-arginine (

Huogen Liu, Xin Wan, Yundi Shi, Fengming Huang, Hailin Shu, Rijin Huang, Ling Gu Department of Critical Care Medicine, Mindong Hospital Affiliated to Fujian Medical University, Fu’an City, Fujian Province, 355000, People’s Republic of ChinaCorrespondence: Ling GuDepartment of Critical Care Medicine, Mindong Hospital Affiliated to Fujian Medical University, No. 89 Heshan Road, Fu’an City, Fujian Province, 355000, People’s Republic of ChinaEmail green660405@163.comBackground: Neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to reflect early renal dysfunction. We investigated the predictive significance of serum NGAL in predicting cardiovascular (CV) death in an old-age population with coronary heart disease (CHD).Methods: In total, 633 CHD patients with a stable clinical condition were enrolled. The measurements of serum NGAL and other laboratory indices were performed within 24 hours after admission. Adjusted analysis was used to assess relationships between serum NGAL and CV death during the 10-year follow-up period.Results: Multivariate logistic regression analysis demonstrated that elevated NGAL levels were related to a higher prevalence of CV disease history [quartile 4, 2.41 (1.60– 4.59), P-trend < 0.001]. The Kaplan–Meier curve indicated that patients with high NGAL levels tended to have a higher rate of CV death than patients with low NGAL levels. A multivariate Cox model suggested that increased levels of NGAL were independently linked with elevated risk of CV death (HR=2.62, 95% CI 1.51– 4.96, P< 0.001) during the 10-year follow-up period, after adjusting for related confounding factors using sensitivity analysis. Furthermore, the receiver operating characteristics (ROC) curve demonstrated that serum NGAL (AUC=0.917, 95% CI 0.895– 0.940, P< 0.001) had an ideal predictive value in predicting CV death.Conclusion: Serum levels of NGAL were elevated in patients with CHD and may be a new parameter that could independently predict CV death in these patients, which may strengthen its potential application in clinical practice.Keywords: neutrophil gelatinase-associated lipocalin, cardiovascular death, ischemic heart disease

Background: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a valuable biomarker of urinary tract infection (UTI) in children.Purpose: This study aimed to compare the diagnostic accuracy of urinary NGAL (uNGAL) with those of serum C-reactive protein (CRP) and white blood cell (WBC) count for predicting UTI and acute pyelonephritis (APN) in febrile children.Methods: The medical charts of children undergoing uNGAL measurements between November 2017 and August 2019 were retrospectively reviewed. Patients with a suspected or diagnosed UTIs were included. The diagnostic accuracies of uNGAL, serum CRP, and WBC count for detecting UTI and APN were investigated. Independent predictors of UTI and APN were investigated using multivariable logistic regression analyses.Results: A total of 321 children were enrolled in this study. The uNGAL levels were higher in the UTI group (n=157) than in the non-UTI group (n=164) (P

Background: Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods: We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI >48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results: At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00-0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC

La evaluación de la función renal se ha realizado históricamente en base a la medición de la tasa de filtración glomerular, la cual fue reemplazada, posteriormente, por la determinación de creatinina sérica debido a su amplia disponibilidad y accesibildad. Sin embargo, en los trabajos actuales, cuando es comparada con el aumento de los biomarcadores de injuria renal aguda (IRA), se observa que la elevación desde su valor basal ante una lesión renal repentina sucede horas más tarde que el Neutrophil Gelatinase-Associated Lipocalin (NGAL) urinario. El objetivo de la presente revisión sobre NGAL, y sus alcances como marcador biológico temprano de injuria renal aguda, es conocer su validación como tal y su aplicabilidad en la práctica médica de pacientes caninos, ya que la identificación temprana de un proceso que altere la funcionalidad y viabilidad de los riñones, permite intervenir de manera terapéutica y anticiparse a un grado irreversible de lesión renal. El método utilizado para la revisión fue consultar revistas científicas internacionales y, sobre estas, seleccionar trabajos de la última década que demuestran resultados estadísticamente significativos sobre el aumento de NGAL entre dos (2) y doce (12) horas antes que la creatinina. Si bien los datos aportados por los trabajos de investigación son claros, aún queda un camino por recorrer en relación a los tipos de injuria renal aguda y sus diferentes causas. NGAL, como biomarcador renal, presente un espectro favorable en cuanto a utilidad clínica, dada la accesibilidad a los métodos complementarios que permiten valorarlo en medicina veterinaria.

Acute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients.172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed.In this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898.This study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.

Objective: To evaluate the benefit of urine neutrophil gelatinase-associated lipocalin (NGAL) measurement to predict the ureteral patency in pediatric patients undergoing pyeloplasty. Materials and Methods: Ureteropelvic junction obstruction patients who underwent unilateral dismembered pyeloplasty had urine NGAL measurements taken intraoperatively during pyeloplasty and postoperatively at six months following surgery. All patients were evaluated preoperatively and postoperatively with renal scans. Pairwise comparisons and correlation analyses were performed to determine the dynamics and benefits of urine NGAL measurement. Results: Thirteen patients were included in this pilot study with a mean age of 3.2 years at surgery. Mean intraoperative bladder urine level was 4.43 ng/mL, and median intraoperative renal pelvic urine NGAL level was 3.70 ng/mL. There was no significant difference between these two levels (p-value = 0.76). Six months after pyeloplasty, 9/13 patients demonstrated significant reduction in the bladder urine NGAL level (at least 50% reduction), and 5/13 patients showed ureteral patency based on postoperative renal scan (more than 5% improvement in differential renal function or the conversion of diuretic half time. However, the finding of significant reduction of urine NGAL level did not correlate with ureteral patency (r = -0.50, p-value = 0.08). Conclusion: Although bladder urine NGAL level reduces in most pediatric patients following pyeloplasty, this decline is not reflective of the finding of ureteral patency from renal scanning. The benefits of urine NGAL measurement in this context remain unclear and require further large-scale investigation.

Background Liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) are candidate biomarkers for the detection of early chronic kidney disease (CKD) in cats. Objective To evaluate urinary and serum L-FABP and NGAL concentrations in CKD cats and in hyperthyroid cats before and after radioiodine (I-131) treatment. Animals Nine CKD cats, 45 healthy cats and hyperthyroid cats at 3 time points including before (T0, n = 49), 1 month (T1, n = 49), and 11 to 29 months after (T2, n = 26) I-131 treatment. Methods Cross-sectional and longitudinal study. Serum L-FABP (sL-FABP), serum NGAL (sNGAL), urinary L-FABP (uL-FABP), and urinary NGAL (uNGAL) were compared between the 3 groups and between hyperthyroid cats before and after treatment. Data are reported as median (min-max). Results CKD cats had significantly higher sL-FABP (13.50 [3.40-75.60] ng/ml) and uL-FABP/Cr (4.90 [0.97-2139.44] mu g/g) than healthy cats (4.25 [1.34-23.25] ng/ml; P = .01 and 0.46 [0.18-9.13] mu g/g; P < .001, respectively). Hyperthyroid cats at T0 had significantly higher uL-FABP/Cr (0.94 [0.15-896.00] mu g/g) than healthy cats (P < .001), thereafter uL-FABP/Cr significantly decreased at T2 (0.54 [0.10-76.41] mu g/g, P = .002). For the detection of CKD, uL-FABP/Cr had 100% (95% confidence interval [CI], 66.4-100.0) sensitivity and 93.2% (95% CI, 81.3-98.6) specificity. There were no significant differences in sNGAL and uNGAL/Cr between the 3 groups. Conclusions and Clinical Importance L-FABP, but not NGAL, is a potential biomarker for the detection of early CKD in cats. Utility of uL-FABP to predict azotemia after treatment in hyperthyroid cats remains unknown.

Background/Aims: We investigated whether serum neutrophil gelatinase-associ ated lipocalin (NGAL) can predict mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Methods: This study enrolled 169 patients who underwent serum NGAL testing at CRRT initiation from June 2017 to January 2019. The predictive power of se rum NGAL level for 28-day mortality was compared to the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score and Sequential Organ Failure Assessment (SOFA) score via area under the receiver operating characteristic curve (AuROC) value. Results: There were 55 survivors and 114 non-survivors at 28 days post-CRRT ini tiation. Median serum NGAL level was significantly higher in the non-survivor group than in the survivor group (743.0 ng/mL vs. 504.0 ng/mL, p = 0.003). The AuROC value of serum NGAL level was 0.640, which was lower than APACHE-II score and SOFA score values (0.767 and 0.715, respectively). However, in the low APACHE-II score group (< 27.5), AuROC value of serum NGAL was significantly increased (0.698), and it was an independent risk factor for 28 day-mortality (haz ard ratio, 2.405; 95% confidence interval, 1.209 to 4.783; p = 0.012). Conclusions: In patients with AKI requiring CRRT, serum NGAL levels may be useful for predicting short-term mortality in those with low APACHE-II scores.

Background: This study aimed to evaluate the ascitic Neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic biomarker for bacterial translocation or bactDNA translocation in ascites of cirrhotic patients and to evaluate the urinary NGAL for identifying renal dysfunction in patients with liver cirrhosis. Methods: This study included 44 patients with ascites. Study participants were divided into two groups. Group (1) had 22 patients with neutrocytic ascites and/or positive ascitic fluid (AF) culture while group (2) included 22 patients with culture negative non neutrocytic ascites (CNNNA), recruited as controls. AF and urine samples were collected from all studied participants. ELISA kit was used for measurement of NGAL levels in AF and urine. DNA extraction and PCR were done. Results: Values of NGAL in ascitic fluid were statistically significantly higher in bactDNA positive group. At cutoff 143.9 ng/ml, ascites NGAL had 86.4% sensitivity, 45.5% specificity, 61.3% positive predictive value (PPV) and 76.9% negative predictive value (NPV). When comparing ascites NGAL between bactDNA positive and negative group, NGAL has a sensitivity of 86.2% and a specificity of 46.7%, PPV of 75.8%, NPV of 63.6%. As for urine NGAL, patients with AKI had statistically significant higher levels of NGAL. Urine NGAL achieved sensitivity of 77.3%, specificity of 50%, PPV of 60.7%, NPV of 68.75%. Conclusion: Early and accurate diagnosis of BT or bactDNA translocation can be aided by utilizing NGAL especially in ruling out infection in those reported to have negative culture results, besides, it can help in early detection of complication of cirrhosis and infection especially AKI helping in the improving the prognosis of cirrhotic patients. It is an advantage that a single marker can detect both infection and kidney injury.

Objectives: Evaluation of urinary neutrophil gelatinase-associated lipocalin (UNGAL) and kidney injury molecule 1 (UKIM-1) as early predictors of development of acute kidney injury (AKI) in patient...

Many hypotheses underlie the pathogenesis of preeclampsia. This study aims to evaluate Neutrophil gelatinase-associated lipocalin (a marker of immune hypothesis) and Neutrophil / Lymphocyte ratio (a marker of inflammation) in the diagnosis of preeclampsia and its severity and to determine the correlation between them.Study design : This randomized case-control study involved 132 pregnant women ; 88 were diagnosed with PE (divided into non-severe and severe groups), and 44 healthy pregnant women as a control group. Results : The mean serum level of NGL was significantly higher in PE (535.37 ± 158.61 ng / ml for severe PE, 522.5 ± 106.3 ng / ml for non-severe PE, and 161.96 ± 17.48 ng / ml for the control group). The ROC Curve NGL criteria of more than 204.4 ng / ml showed 100% sensitivity and specificity in both severe and non-severe cases versus control. The N / L ratio showed a significant difference (5.81 ± 5.24 for severe PE, 4.1 ± 3.41 for non-severe PE, and 3.89 ± 1.79 for the control group), but the ROC curve criterion was not significant. Both showed a non-significant positive correlation. Conclusion : NGL is an excellent diagnostic factor, whereas N / L might have lower diagnostic performance compared with NGL. Both are related independently to the pathophysiology of PE. J. Med. Invest. 68 : 321-325, August, 2021.

Oxidative stress has been implied in cellular injury even in the early phases of multiple sclerosis (MS). In this study, we quantified levels of biomarkers of oxidative stress and antioxidant capacity in cerebrospinal fluid (CSF) in newly diagnosed MS patients and their associations with brain atrophy and iron deposits in the brain tissue. Consecutive treatment-naive adult MS patients (n = 103) underwent brain MRI and CSF sampling. Healthy controls (HC, n = 99) had brain MRI. CSF controls (n = 45) consisted of patients with non-neuroinflammatory conditions. 3T MR included isotropic T1 weighted (MPRAGE) and gradient echo (GRE) images that were processed to quantitative susceptibility maps. The volume and magnetic susceptibility of deep gray matter (DGM) structures were calculated. The levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-iso prostaglandin F2α (8-isoPG), neutrophil gelatinase-associated lipocalin (NGAL), peroxiredoxin-2 (PRDX2), and malondialdehyde and hydroxyalkenals (MDA + HAE) were measured in CSF. Compared to controls, MS patients had lower volumes of thalamus, pulvinar, and putamen, higher susceptibility in caudate nucleus and globus pallidus, and higher levels of 8-OHdG, PRDX2, and MDA + HAE. In MS patients, the level of NGAL correlated negatively with volume and susceptibility in the dentate nucleus. The level of 8-OHdG correlated negatively with susceptibility in the caudate, putamen, and the red nucleus. The level of PRDX2 correlated negatively with the volume of the thalamus and both with volume and susceptibility of the dentate nucleus. From MRI parameters with significant differences between MS and HC groups, only caudate susceptibility and thalamic volume were significantly associated with CSF parameters. Our study shows that increased oxidative stress in CSF detected in newly diagnosed MS patients suggests its role in the pathogenesis of MS.

Objective: To evaluate the serum neutrophil gelatinase-associated lipocalin levels in pregnant women with and without preeclampsia, early-onset preeclampsia and late-onset preeclampsia, preeclampsia with and without severe features, and investigate the correlation with the neonatal outcomes.Study Design: A total of 79 pregnant women, 27 with uncomplicated pregnancies, 30 with early-onset preeclampsia, and 22 with late-onset preeclampsia were evaluated in a cross-sectional study. Neutrophil gelatinase-associated lipocalin was measured with a colorimetric Sandwich-ELISA method. Age; body mass index; systolic and diastolic blood pressure; umbilical-artery Doppler results; serum urea, bilirubin, uric acid, AST, ALT; 24-hour protein test; birth-weight; and Apgar-scores were recorded.Results: Serum neutrophil gelatinase-associated lipocalin levels were significantly higher in women with preeclampsia compared to those without preeclampsia (p

Introduction: Detecting AKI in a timely fashion with the current AKIN staging criteria is a challenge because the diagnosis of AKI is usually based on changes in serum creatinine (SCr) which is a poor marker of early renal dysfunction. Aim: To study the role of Serum Neutrophil Gelatinase-Associated Lipocalcin (NGAL) as early biomarker for the detection of Contrast induced acute kidney injury (CIAKI) in subjects undergoing Percutaneous transluminal coronary angiogram (PTCA) with normal eGFR. Materials and Methods: Prospective cohort study was conducted, where SCr and serum NGAL were serially measured in a heterogeneous group of subjects (n=60) presenting to cardiology department. Results: The study population consisted of 60 subjects. All subjects were divided into 2 groups “CIAKI group” and “no-CIAKI group” according to predefined definition. The serum NGAL increased and reached its peak at 4 hours after contrast media (CM) administration and did not returned to baseline by 24 hours while the SCr increased at 24 hours and reached peak at 48 hours respectively (P

STUDY DESIGN Secondary analysis of urine samples collected from a prospective within-subject clinical trial. OBJECTIVES Describe the baseline variation in urine neutrophil gelatinase-associated lipocalin (uNGAL) levels in adults with neurogenic lower urinary tract dysfunction (NLUTD) and determine if uNGAL levels vary according to likelihood of having a UTI. SETTING Greater Washington D.C. region. METHODS Urine samples were collected from a cohort of adults with NLUTD from a clinical trial. Samples were divided into groups of "Not UTI", "Unlikely UTI", and "Likely UTI" based on symptoms and urine culture results. uNGAL was compared between groups using Kruskal-Wallis and post hoc Dunn's test. Mixed effects logistic model was used to assess the association of uNGAL and Likely UTI. RESULTS Twenty-seven participants provided a total of 104 samples. uNGAL levels were lowest for the No UTI group (n = 29; 37 ng/ml interquartile range (IQR) (15, 71)), intermediate for the Unlikely UTI group (n = 67; 95 ng/ml IQR (37, 161)) and highest for the Likely UTI group (n = 8; 187 ng/ml IQR(146, 224)). uNGAL levels were higher in those with Likely UTI compared to both Unlikely UTI (p

Introduction: Acute kidney injury following cardiac surgery is a frequent complication associated with increased mortality and morbidity. Minimal invasive extracorporeal circulation is suggested to preserve postoperative renal function. The aim of this study was to assess the impact of minimal invasive versus conventional extracorporeal circulation on early postoperative kidney function. Methods: Randomized controlled trail including 60 patients undergoing elective stand-alone coronary artery bypass graft surgery and allocated in a 1:1 ratio to either minimal invasive (n = 30) or conventional extracorporeal circulation (n = 30). Postoperative kidney injury was assessed by elevation of plasma neutrophil gelatinase-associated lipocalin (NGAL), a sensitive tubular injury biomarker. In addition, we assessed changes in estimated glomerular filtration rate (eGFR), and the incidence of acute kidney injury according to the Acute Kidney Injury Network (AKIN) classification. Results: We observed no differences between groups regarding increase of plasma NGAL (p = 0.31) or decline of eGFR (p = 0.82). In both groups, 6/30 patients developed acute kidney injury according to the AKIN classification, all regaining preoperative renal function within 30 days. Conclusion: Our findings challenge the superiority of minimal invasive compared to conventional extracorporeal circulation in terms of preservation of renal function following low-risk coronary surgery.

Background. To evaluate the ratio of acute kidney injury (AKI) to chronic kidney disease (CKD) in sepsis-associated acute kidney injury (SA-AKI) patients of the intensive care unit (ICU) and predictive value of neutrophil gelatinase-associated lipocalin (NGAL) measured at the admission time in the progression of AKI to CKD. Methods. A study of 121 consecutive adult patients admitted to the intensive care unit (ICU) diagnosed as SA-AKI. AKI and CKD were defined based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Glomerular filtration rate (GFR) was calculated by the CKD-EPI formula. Serum and urine NGAL was measured using the BioVendor Human Lipocalin-2/NGAL ELISA with a blood sample taken at hospital admission time. Results. The ratio of AKI to CKD in SA-AKI patients was 22.3%. Mean concentration of serum and urine NGAL in AKI to the CKD group was 790.99 ng/ml and 885.72 ng/ml, higher significantly than those of recovery patients (351.86 ng/ml and 264.68 ng/ml), p<0.001. eGFR, both serum and urine NGAL had a predictive value for AKI to CKD (eGFR: AUC=0.857, Se=74.1%, Spe=92.6%, p<0.001. Serum NGAL: AUC=0.868, Se=77.8%, Spe=91.5%. Urine NGAL: AUC=0.869, Se=77.8%, Spe=92.6%, p<0.001. Conclusion. Serum and urine NGAL, measuring at hospital admission time, were good prognostic biomarkers of AKI to CKD in SA-AKI patients.

Objective: The role of neutrophil gelatinase-associated lipocalin in renal obstruction remains unclear. The aim of this study is to assess neutrophil gelatinase-associated lipocalin kinetics and its potential role as a biomarker of renal damage in acute ureteric colic. Methods: Thirty-six patients with acute ureteric colic were prospectively recruited and compared with two control groups. Blood and urine samples for plasma neutrophil gelatinase-associated lipocalin and urinary neutrophil gelatinase-associated lipocalin levels were obtained at various time points. Results: There were significantly higher levels of urinary neutrophil gelatinase-associated lipocalin and the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio at presentation when comparing patients with acute ureteric colic to healthy controls ( P=0.002 and P=0.004, respectively). In patients with acute ureteric colic managed with surgical intervention ( n=27) there was a significant reduction in plasma neutrophil gelatinase-associated lipocalin ( P=0.001) and an increase in the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio 6 hours postoperatively ( P=0.03). Eight of nine patients managed conservatively for acute ureteric obstruction had spontaneous stone passage at follow-up (median 26 days) with a significant reduction in the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio ( P=0.03). Conclusion: The observation of a reduction in plasma neutrophil gelatinase-associated lipocalin and urinary neutrophil gelatinase-associated lipocalin levels following relief of renal obstruction due to ureteric stones suggests the potential role of neutrophil gelatinase-associated lipocalin as a biomarker in this scenario and in the follow-up setting as a potential marker of relief of obstruction. Level of evidence: 3b

Background: Breast cancer (BC) is the most common cause of malignancy in females all over the world. Continuous scientific research for the discovery of new markers helping is a cornerstone for early disease detection and proper management. Aim of the Study: This study aimed to evaluate the role of Neutrophil gelatinase-associated lipocalin (NGAL) as prognostic markers for breast cancer in an Egyptian female population. Patients and Methods: 120 BC patients and 30 healthy controls were the subjects of the study; serum NGAL levels were investigated and correlated with the clinicopathologic characteristics of the BC patients. Results: Our study showed that NGAL was significantly different between healthy controls and BC patients, and it revealed a gradual increase with disease severity. Conclusion: Our findings suggested that NGAL could be diagnostic marker for early case detection, and was shown to be associated with breast cancer prognosis, supporting its role as prognostic biomarker.

Introduction: Chronic kidney disease (CKD) is one of the most threatening and important disorders worldwide in both industrial and developing nations. In addition, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) are three factors suggested as diagnostic and prognostic biomarkers in CKDs. Considering the lack of enough efficiency of the creatinine in the prognosis of the CKD, the present study aimed to assess the relationship between these three factors and CKD occurrence and determine if they could be considered valid biomarkers in this regard. Materials and Methods: The present case-control study was designed enrolling 42 patients with confirmed CKD referring to the Imam Khomeini hospital of Kangan. The participants were 42 years old and gender-matched healthy counterparts. Blood samples were obtained, and then NGAL, KIM-1, and L-FABP were determined by the enzyme-linked immunosorbent assay using commercial kits (Bioassay Technology Laboratory). Finally, the serum creatinine was detected by applying Jaffe’s method. Results: Based on the results, significant differences were found in the serum levels of all four factors between CKD patients and the control group. More precisely, the serum levels of NGAL (P < 0.0001, specificity: 87.6%, sensitivity: 79.3%, and the area under the curve, AUC: 0.89), L-FABP (P < 0.0001, specificity: 83.3%, sensitivity: 78.3%, and AUC: 0.86), KIM-1 (P < 0.0001, specificity: 85.7%, sensitivity: 78.6%, and AUC: 0.88), and creatinine (P < 0.0001) were significantly higher in individuals with CKDs in comparison with controls. Eventually, the serum levels of NGAL, L-FABP, and KIM-1 were significantly correlated with each other in both patient and control groups (P < 0.0001). Conclusion: In general, NGAL, L-FABP, KIM-1, and creatinine could be used as independent biomarkers for the diagnosis of CKD. Moreover, the measurement of NGAL, L-FABP, and KIM-1 altogether could be a valid assessment for the diagnosis of CKD.

Introduction: Detection of activity of ulcerative colitis (UC) is vital for predicting treatment outcome. The assessment depends on clinical, serologic, and endoscopic findings. One of the noninvasive biomarkers for disease activity detection is serum Neutrophil Gelatinase-Associated Lipocalin (NGAL). Aim: To assess the relationship between NGAL and endoscopic, histopathologic and clinical activity of UC. Methods: This study was conducted on 50 cases with definitive diagnosis of UC and 15 cases with normal colonoscopy examination as controls. UC cases were considered active if Geobes score was ≥3.1. Complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and liver and kidney function tests were done. Serum NGAL was estimated using ELISA technique. Results: UC cases were classified into active group (n = 36) and inactive group (n = 14). In active UC cases, median value (IQR) of serum NGAL was significantly increased (101.15 (67.53 – 156.40) ng/mL) compared to inactive cases (63.35 (60.98–65.20) ng/mL) and control group (24.80 (15.50 – 31.50) ng/mL). Serum NGAL was well correlated with Geobes score, Mayo score, CRP and ESR. Serum NGAL at cut-off ≥ 63 can predict activity with sensitivity 88.89%, specificity 85.71%, PPV 94.12% and NPV 75%. Conclusion: Serum NGAL is valuable noninvasive marker for assessment of UC disease activity.

Our study evaluates the effects of aminophylline in the reduction of NGAL levels in perinatal asphyxia.Term neonates with hypoxic ischaemic encephalopathy who were divided into two groups, the treatment and placebo. Urine NGAL levels were measured on day one and four of the treatment using BIOPORTO kits in both the groups.Day 1 NGAL levels were not statistically different in either group irrespective of the age, gender and the mode of delivery. on 4Following the treatment with aminophylline, NGAL levels in asphyxiated neonates are likely to reduce. Further studies based on other kidney dysfunction parameters can lead to the better and accurate conclusions.

Neutrophil gelatinase-associated lipocalin (NGAL) may be a biomarker candidate for brain injury and a novel therapeutic target in ischemic stroke. Epidermal growth factor (EGF) has protective effects on ischemic injury via activating EGF receptor (EGFR). Whether the protection mechanism of activating EGF-EGFR axis against brain injury is involved in regulating NGAL is still unknown. In the present study, we attempted to explore the expression of NGAL in ischemic brain and the effects of EGF on the NGAL expression in a mouse model of middle cerebral artery occlusion (MCAO). Results suggested that the NGAL expression in ischemic brain was markedly increased after cerebral ischemic damage, and specific NGAL-siRNA can attenuate ischemia-triggered infarct volume and neurological deficit. Then, we found that intracerebroventricular EGF treatment may reduce the level of NGAL in ischemic brain, accompanied by functional improvements. Meanwhile, specific JAK2/STAT3 inhibitor AG490 can reverse EGF-induced reduction of NGAL level. Therefore, the elevated NGAL level in ischemic brain may be an important participant in ischemic brain injury. EGF/EGFR activation ameliorated infarct volume of brain tissues and neurological deficit, and the underlying mechanism is involved in regulating the expression of NGAL via the activation of JAK2/STAT3 pathway.

Renal toxic injury can neither be predicted nor quantified exactly by the serum creatinine level. NGAL is a promising biomarker for early detection of AKI due to different causes. Our objective was to evaluate it�s value in the setting of nephrotoxic injury. We performed an experiment in which we administered gentamicin, atropine and fipronil at different doses to the laboratory mice to quantify the evolution of creatinine and NGAL. Compared to creatinine, NGAL increased faster and was detected at elevated levels from the first 4 h after administration of both low and high dose gentamicin. Fipronil, atropine and the combination caused a significant increase in NGAL serum values at 4 hours, an increase that lasted up to 24 and 72 h , respectively, compared to the control group, Its highest levels were recorded at 4 h. Compared to creatinine, NGAL increased faster and was detected at elevated levels from the first 4 h after administration of fipronil, atropine and the combination of them.

Background The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. Methods This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. Results NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01-1.14]), Interleukin-6 (1.51 [1.01-2.26]), midkine (1.01 [1.00-1.02]), 1-hepcidin-25 (1.08 [1.00-1.17]), and NGAL/hepcidin-ratio (2.91 [1.30-6.49]) were independent predictors of MAKE and AKI (1.38 [1.03-1.85], 1.08 [1.01-1.15], 1.01 [1.00-1.02], 1.09 [1.01-1.18], and 3.45 [1.54-7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. Conclusions NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.

BACKGROUND: Sepsis is a complex interaction between the direct toxic effects of infecting microor ganisms and the disruption of the host's normal inammatory response to infection. One organ that is often disrupted is the kidney . Neutrophil Gelatinase-Associated Lipocalin (NGAL) is an AKI biomarker that can be used as an early biomarker for AKI prediction, monitoring clinical trials in AKI and for the prognosis of AKI. METHOD: This research is an observational study. 30 subjects with sepsis were examined for PCT, BUN, urea, creatinine and urine NGAL tests. RESULTS: Statistical analysis using the Spearman Rank Test shows that NGAL level 1 has a signicant relationship with PCT day 1, with a value (r = 0.912) and a value of p 0.05). NGAL day 3 had a signicant relationship with PCT day 1, with a value (r = 0.0771) and a p value

Purpose Understanding the pathogenesis and the molecular mechanisms of diabetic nephropathy (DN) helps its timely detection and prevention. The current work aims tomeasure serum sestrin 2 and betatrophin levels in healthy and type diabetic (T2DM)subjects with/or without diabetic nephropathy (DN) and also to test their correlation with serum neutrophil gelatinase associated lipocalin (sNGAL); indicator of DN. Methods This study included 96 subjects; 20 healthy (G1) and 76 T2DM [22 normoalbuminuric (G2), 35 microalbuminuric (G3) and 19 macroalbuminuric (G4)]. Serum sestrin 2, betatrophin and NGAL were measured by their corresponding kits. Results Significant low levels of serum sestrin 2 andhigh levels of serum betatrophin were found in T2DM group when compared to G1 (p = 0.002,p > 0.001, respectively) and this difference is manifested in G4 followed, in order, by G3, G2 then G1 (p= > 0.001 for both). Also, serum sestrin2 levels showed significant negative correlations with sNGAL in G1 (r = −0.497, p = 0.026), G2 (r = −0.784, p > 0.001), G3 (r = −0.894, p > 0.001) and G4 (r = −0.896, pp. > 0.001) while serum betatrophin levels showed significant positive correlations with sNGAL in G2 (r = 0.681, p > 0.001), G3 (r = 0.518, p > 0.001) and G4 (r = 0.727, p > 0.001). Conclusion Serum sestrin 2 levels decrease significantly while betatrophin levels increase significantly in T2DM patients with DN especially those with macroalbuminuria. These levels have significant effect strengths on the indicator of diabetic nephropathy; sNGAL which might indicate theirvaluablerole in the timely detection and prevention of the development of DN.

Objective:The objective of this article is to study the correlation between neutrophil gelatinase-associated lipocalin (NGAL) and soluble CD14 subtype (presepsin) on the severity and prognosis evaluation of acute paraquat poisoning (APP) patients.Materials and methods:We studied 120 APP patients who were divided into three groups: light (28 cases), moderate (52 cases), and heavy poisoning (40 cases) groups. Twenty healthy volunteers were enrolled as controls.Results:Acute kidney injury (AKI) occurred in 86 APP patients (71.7%, 86 of 120). In AKI group, urine NGAL was elevated 3 h after treatment, serum NGAL was elevated 24 h after treatment, and serum creatine (SCr) was elevated 2 days after treatment, which were all significantly higher than non-AKI group. Compared with control group, there were significant differences in presepsin and acute physiology and chronic health status (APACHE) II score of different poisoning groups. There were significant differences in detection indices 24 h, 3 days, and 7 days after treatment among different poisoning groups. There was a positive correlation between urine NGAL and serum paraquat concentration, urine NGAL, and AKI morbidity ( r1= 0.974, r2= 0.766, p < 0.001), suggesting higher urine NGAL level indicated higher AKI morbidity. Receiver operating characteristic curves analysis suggested serum presepsin level and urine NGAL level had higher sensitivity and specificity than APACHE II score when predicting 28-day mortality of APP patients.Conclusion:Serum and urine NGAL level is elevated earlier than SCr, which is important for the early diagnosis of APP. Serum presepsin and urine NGAL levels can be used as markers to diagnose the severity of AKI and predict the mortality of APP patients.

Aims: This study was designed to evaluate the conflicting association between 2 tubular protein markers including neutrophil gelatinase-associated lipocalin (NGAL) and retinol-binding protein-4 (RBP-4) with albuminuria and glomerular filtration rate (GFR) and calculate the accuracy of the role of NGAL and RBP-4 in diagnosis of diabetic nephropathy (DN) in patients with type2 diabetes. Methods: This is a cross-sectional study that included 133 patients with type 2 diabetes. There were 3 diabetic study groups with normoalbuminuria, moderately increased albuminuria, severely increased albuminuria, and non-diabetic control group without any renal disease. We analyzed the difference of urinary NGAL (uNGAL) and RBP-4 between nondiabetics and diabetics, as well as within the diabetic group. We also assessed the association between albuminuria and NGAL and RBP-4. Results: The urinary levels of NGAL and RBP-4 were higher in patients with type 2 diabetes compared to nondiabetics as well as in albuminuric diabetics compared to nonalbuminuric patients with diabetes (p value p < 0.01). Moreover, areas under the curve of NGAL and RBP-4 for the diagnosis of chronic kidney disease were 80.6 and 74.6%, respectively. Conclusion: uNGAL and RBP-4 are potential markers of tubular damage that may increase before the onset of glomerular markers such as albuminuria and GFR in patients with type 2 diabetes. Therefore, these markers can be used as complementary measurements to albuminuria and GFR in the earlier diagnosis of DN.

To evaluate the efficacy of renal resistance indices (RRIs) and neutrophil gelatinase-associated lipocalin (NGAL) for early prediction of occurrence and severity of acute kidney injury in patients ...

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for the diagnosis of diabetic kidney disease (DKD), but its utility is currently debated. This meta-analysis aims to evaluate the diagnostic value of NGAL for DKD. Method: MEDLINE, Embase, ­Cochrane Library, CNKI, and CBM databases were searched up to April 13, 2019. In bivariate random-effect models, the diagnostic performance of NGAL for DKD was assessed using pooled estimates of sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and hierarchical summary receiver-operating characteristic analysis. Results: Nineteen studies were eligible for the meta-analysis. Serum NGAL had a pooled sensitivity and specificity of 0.79 (95% confidence intervals [CI] 0.60–0.91) and 0.87 (0.75–0.93) (7 studies, 1,238 patients). The pooled positive likelihood ratio (LR+) and negative likelihood ratio (LR–) were 5.97 (3.03–11.76) and 0.24 (0.11–0.51). For urine NGAL, the pooled sensitivity, specificity, LR+, and LR– were 0.85 (0.74–0.91), 0.74 (0.57–0.86), 3.26 (1.87–5.67), and 0.21 (0.12–0.35), respectively (10 studies, 1,369 patients). The pooled sensitivity and specificity for kidney disease in normoalbuminuric patients with diabetes was 0.90 (0.82–0.95) and 0.97 (0.90–0.99) for both serum NGAL and 0.94 (0.87–0.98) and 0.90 (0.81–0.96) for urine NGAL (4 studies, 221 patients). NGAL appeared to perform similarly in subgroup analysis. Conclusion: The meta-analysis has shown that NGAL may be useful for DKD classification and also has a potential diagnostic value for normoalbuminuric kidney disease. Large-scale prospective studies are required to clarify its role in the diagnosis and risk stratification of patients with DKD.

Objectives: To evaluate serum neutrophil gelatinaseassociated lipocalin (NGAL) concentrations of pregnant women complicated with coronavirus disease 2019 (COVID-19) and investigate its diagnostic value for the severity of COVID-19. Methods: Of the 46 pregnant women with COVID-19 included in the study, we further classified these women into 2 subgroups: the non-severe COVID-19 group (n=25) and the severe COVID-19 group (n=21). Results: Neutrophil gelatinase-associated lipocalin plasma concentrations were significantly higher in pregnant women complicated with severe COVID-19 (90 [53.1-207.7] ng/ml) compared to those from Original Article pregnant women with non-severe COVID-19 (51.8 [39.6-70.3] ng/ml) and healthy pregnant women (44.3 [32.2-54.1] ng/ml, p

Background Systemic inflammatory response occurs by sepsis and invasive surgery. Recent articles suggest that not only CRP but also procalcitonin, presepsin, and neutrophil gelatinase-associated lipocalin may reflect the severity of systemic inflammation. In addition, as systemic inflammation could degenerate orexin neurons, plasma orexin A might also be a good biomarker to predict the severity. Thus, we have determined relation between plasma biomarker and severity of illness score in patients with systemic inflammation. Methods Previous database (UMIN000018427) was used to secondly determine which plasma biomarkers may predict the severity of illness in the ICU patients with systemic inflammation (n = 57, 31 non-sepsis surgical patients and 26 sepsis patients). We measured plasma levels of orexin A, CRP, procalcitonin, presepsin, and neutrophil gelatinase-associated lipocalin were measured, and APACHE II score was assessed in these patients at their admission to the ICU. Data are shown as mean ± SD. Statistical analyses were done with unpaired t test. The correlation between APACHE II score and plasma biomarkers were examined using Pearson’s correlation coefficient and a least squares linear regression line. Results Demographic data did not differ between sepsis and non-sepsis groups. However, APACHE-II score was significantly higher in sepsis group than those in non-sepsis group (20.9 ± 6.6 vs 15.8 ± 3.2, p < 0.01). There were significant correlations between APACHE II score and plasma CRP (r = 0.532, p < 0.01), procalcitonin (r = 0.551, p < 0.01), presepsin (r = 0.510, p < 0.01), and neutrophil gelatinase-associated lipocalin (r = 0.466, P < 0.01) except orexin A. Conclusion All plasma biomarkers tested except orexin A may reflect the severity of illness in patients with systemic inflammation.

Einleitung: Die akute Nierensch��digung (AKI) hat eine hohe Pr��valenz bei hospitalisierten Patienten und ist mit ung��nstigen klinischen Verl��ufen assoziiert. Neue Biomarker, wie neutrophil gelatinase-associated lipocalin (NGAL), verbessern zwar die fr��he Detektion einer AKI, k��nnen jedoch von diversen St��rfaktoren beeinflusst werden. Wir haben cation transport regulator homolog 1 (CHAC1) in einem Mausmodell der Nierensch��digung durch Isch��mie-Reperfusion (IRI) als potenziellen neuen Biomarker der hyperakuten Nierensch��digung identifiziert. Ziel dieser Arbeit ist die ��bertragung der Ergebnisse in ein klinisches Setting. Hierzu wurde zun��chst ein Western Blot-Protokoll entwickelt, das zur Messung von CHAC1 im Urin bei einer Kohorte von Patienten verwendet wurde, bei denen durch unilaterales Abklemmen der Nierenarterie w��hrend einer Teilnephrektomie eine IRI induziert wurde. Zus��tzlich wurde eine Fallserie mit Patienten mit verschiedenen AKI-Formen zusammengestellt, um potenziell vielversprechende klinische Szenarien f��r zuk��nftige Studien zu identifizieren. Methoden: Die Studienpopulation bestand aus 37 Patienten, von denen 27 eine Teilnephrektomie mit unilateralem Abklemmen der Nierenarterie erhielten (Gruppe 1). 10 Patienten erhielten eine Teilnephrektomie ohne renale Isch��mie (Gruppe 2). Urinproben wurden pr��operativ sowie einmal t��glich im postoperativen Verlauf entnommen. Die Fallserie umfasste 15 Patienten mit verschiedenen AKI-Formen und 26 Patienten ohne AKI (Kontrollgruppe), von denen jeweils eine Urinprobe gesammelt wurde. CHAC1 im Urin wurde mittels Western Blot gemessen. Die Ergebnisse wurden mittels ImageJ semiquantitativ ausgewertet, wobei f��r alle Messungen eine Kalibrierung zu bekannten Konzentrationen von rekombinantem CHAC1 durchgef��hrt wurde. NGAL und Calprotectin im Urin wurden mittels enzyme-linked immunosorbent assay (ELISA) gemessen. Ergebnisse: Die Patienten in Gruppe 1 wiesen sechs Stunden postoperativ sowie bis zum dritten postoperativen Tag signifikant h��here CHAC1-Konzentrationen auf als pr��operativ. In Gruppe 2 war postoperativ kein signifikanter Anstieg der CHAC1-Konzentration zu beobachten. Die h��chste CHAC1-Konzentration wurde in Gruppe 1 sechs Stunden nach der Operation erreicht. Es konnte kein signifikanter Unterschied der maximalen postoperativen Konzentrations��nderung von CHAC1 gegen��ber dem pr��operativen Ausgangswert zwischen den beiden Gruppen festgestellt werden (p=0,77). Im Rahmen der Fallserie konnte CHAC1 bei allen AKI-Patienten im Urin gemessen werden und die Konzentrationen lagen signifikant h��her als bei Patienten ohne AKI (p, Introduction: Acute kidney injury (AKI) has a high prevalence among hospital patients and is associated with unfavorable clinical courses. Novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) improve the early detection of AKI, but they are sensitive to stimuli other than kidney injury. We identified cation transport regulator homolog 1 (CHAC1) as a potential new biomarker for early AKI in a mouse model of ischemia-reperfusion injury (IRI). The goal of this project was to translate these findings into a clinical setting. Therefore, I developed a Western Blot protocol to evaluate the utility of urinary CHAC1 in a cohort of patients who underwent unilateral clamping of the renal artery inducing IRI during partial nephrectomy. Secondly, I put together a case series including patients with different forms of AKI to determine promising clinical settings for future research. Methods: The study population consisted of 37 patients. 27 underwent partial nephrectomy with unilateral clamping of the renal artery (group 1). 10 patients underwent partial nephrectomy without renal ischemia (group 2). Urinary samples were collected before surgery and serially after surgery. The case series consisted of 15 patients with different forms of AKI and 26 patients without AKI (control group) donating one urine sample each. Urinary CHAC1 was detected by Western blotting. Semiquantitative analysis of band intensity was performed using ImageJ calibrating to known quantities of recombinant CHAC1 loaded onto adjacent lanes. Urinary NGAL and calprotectin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients undergoing partial nephrectomy with renal ischemia urinary CHAC1-concentrations significantly increased compared to preoperative baseline from 6h up to 3 days after surgery. In group 2 there was no significant increase in CHAC1-concentrations after surgery. Highest CHAC1- concentrations in group 1 were reached 6h after surgery. There was no significant difference in the highest change from baseline CHAC1 after surgery between the two groups (p=0,77). Regarding the case series, CHAC1 was detectable in all samples of AKI patients and concentrations were significantly higher than in patients without AKI (p

Circulating levels of neutrophil gelatinase-associated lipocalin (NGAL) have been associated with acute kidney injury and the severity and progression of chronic kidney disease (CKD). This study investigated its potential utility as a biomarker for the risk of new-onset CKD in a population-based cohort study. Individuals without CKD at baseline (n = 4660) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma NGAL concentrations were investigated for their associations with new-onset CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, urinary albumin excretion (UAE) > 30 mg/24-h, or both. Mean (±SD) plasma NGAL concentrations were 104.0 (±34.7) μg/L and median eGFR was 96 [IQR: 85.3–105.8] mL/min/1.73 m2. After median follow-up of 8.3 [IQR: 7.8–8.9] years, 467 participants developed new-onset CKD. Plasma NGAL concentrations were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.35 [95% CI: 1.11–1.63], p = 0.002), even after adjustment for potentially confounding factors (1.37 [1.09–1.73], p = 0.007) except baseline eGFR (1.09 [0.86–1.37], p = 0.490). In secondary analyses, plasma NGAL concentrations were significantly associated with new-onset CKD as defined by eGFR < 60 mL/min/1.73 m2 alone (adjusted HR per doubling 2.54 [1.69–3.80], p < 0.001), which was abrogated after adjustment for eGFR (1.05 [0.69–1.59], p = 0.828), also when UAE > 30 mg/24-h was set as individual outcome (1.05 [0.82–1.35], p = 0.705). Higher plasma NGAL concentrations are associated with an increased risk of developing CKD in the general population. This association is dependent on renal function, and mainly driven by new-onset CKD as defined by renal function decline.

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.

Background Aortic valve (AV) stenosis is the commonest form of adult valvular heart disease (VHD) and affects 4.5% of the general population aged over 60 years. Owing to multifactorial and complex molecular events, the valve interstitial cell (VIC) undergoes myofibroblast and osteoblast differentiation. Neutrophil gelatinase-associated lipocalin (NGAL) is a pleiotropic glycoprotein belonging to the lipocalin family and it is expressed in a wide range of tissues and cell types. It is deregulated in several diseases with both detrimental and beneficial effects. NGAL mainly signals towards 24p3R. Purpose We aimed to confirm the expression of NGAL in human AV stenosis and its association with inflammation, oxidative stress, fibrosis/remodeling and calcification, and its regulation in calcifying VICs. Methods Surgical AV leftovers were harvested from patients undergoing elective surgical valve replacement with no kidney disease. Serum samples were collected within the 24h before the surgery. AV were histologically assessed by hematoxylin-eosin, Movat, Alizarin Red and Alcian blue/Sirius Red staining and immunohistochemistry. Western blotting, ELISA and zymography were used in molecular biology studies. VICs were challenged for 2, 4 and 8 days with hyperphosphate (2.6mM, HP) media ± rhNGAL for in vitro validation studies. Results NGAL was quantified in AVs and serum samples from 126 donors (57.4% men). Circulating NGAL was associated with circulating inflammation (Tumor Necrosis Factor-α, Interleukin (IL)-6 and ICAM-1) and oxidative stress (Myeloperoxidase (MPO) and 8OHdG) markers. Likewise, tissue NGAL was correlated with inflammation (IL-6, RANTES and Galectin-3), oxidative stress (MPO, Endothelial Nitric Oxide Synthase, Malondialdehyde (MDA) and Carboxy Methyl Lysine (CML)) and fibrosis (Collagen type I). Osteoblast markers, metalloproteinase (MMP)-9 expression or its activity were not associated with NGAL. NGAL was greater expressed in men than women (217.70±23.41 vs. 119.5±11.31, p=0.0098). In vitro, intracellular NGAL and 24p3R were strongly down-regulated in calcifying men-derived VICs (n=6) whereas secretion of NGAL was enhanced from day 4 (0.55±0.15, p=0.0283; 0.32±0.09 p Conclusions NGAL is associated with inflammation, oxidative stress and fibrosis in AV stenosis, and promotes pro-apoptotic and necrotic phenotypes in vitro. Our results suggest that NGAL signaling may drive sex-dependent differences clinically relevant to the VHD pathogenesis. The challenge is now to understand how NGAL signals in men/women-derived VICs. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III

Introduction Lupus nephritis (LN) affects almost two-thirds of Systemic lupus erythematosus (SLE) patients. Despite initial aggressive therapy, up to 25% of patients with LN will progress to end stage renal disease (ESRD). Conventional serum markers for LN lack the sensitivity of an ideal biomarker. Urinary Neutrophil gelatinase-associated lipocalin (UNGAL) is an excellent biomarker for early diagnosis of acute kidney injury and predicting renal outcomes. Objectives To measure UNGAL among LN patients correlating its levels with renal disease activity to investigate its predictive performance in response to induction therapy. Patients and Methods 40 SLE patients with biopsy-proven LN, class III, IV, or V were randomly selected. The study was conducted in internal medicine department and Outpatient clinic in Ain Shams University Hospitals on and completed after six months. UNGAL was measured at baseline and after complete induction therapy. Results In LN patients at baseline; mean UNGAL levels of complete response, partial response, and no response groups were 14.48 ±2.99 ng/ml, 34.49 ±4.09, and 62.07 ±14.44 ng/ml respectively. Based on ROC curve, we found better performance of baseline UNGAL to discriminate complete response group from partial and non-response groups to predict response to induction, outperforming conventional biomarkers. The area under the curve was 0.943 (92.31% sensitivity, 88.89% specificity), and the best cut-off level was 26.5 ng/ml. Conclusion UNGAL performed better than conventional biomarkers in predicting response to treatment of active LN.