Neutrophil Gelatinase-associated Lipocalin Concentrations Research Articles

#2307 Serum NGAL, MMP-9 and suPAR in the assessment of kidney impairment and cardiovascular risk in children and adolescents with type 1 diabetes or obesity

Abstract Background and Aims Type 1 diabetes mellitus (DM1) and obesity represent two chronic paediatric diseases with worryingly rising incidence, characterized by chronic inflammation, endothelial dysfunction and increased risk for kidney impairment and cardiovascular disease. The aim of this cross-sectional study was to explore the potential usefulness of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL), Matrix Metalloproteinase-9 (MMP-9) and Soluble Urokinase Plasminogen Activator Receptor (suPAR) for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity. Method Serum samples were obtained from children and adolescents aged <18 years old with DM1 (n=35) or obesity (n=38) and normal renal function with no history of albuminuria, as well as from healthy controls (n=23). Serum NGAL, MMP-9 and suPAR concentrations were measured using commercially available sandwich ELISA kits (NGAL: (DY1757-05), MMP-9: (DMP900); suPAR: (DUP00); R&D systems). All patients were evaluated for anthropometric indices (weight, height, BMI) while for different degrees of weight status we used the body mass index (BMI) z-score adjusted for age and sex. Estimated glomerular filtration rate (eGFR) was calculated according to the revised bedside Schwartz formula. Results Serum NGAL values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with T1DM with diabetes duration (Spearman rho 0.364, p=0.044), and in all study participants with BMI z-score (Spearman rho 0.401, p=0.004). Furthermore, serum MMP-9 levels were significantly increased in patients with T1DM and in patients with obesity compared to controls. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls (Table 1). Finally, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p<0.001) and creatinine levels (Spearman rho −0.334, p=0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p=0.009). Conclusion Circulating NGAL, MMP-9 levels may prove useful as surrogate biomarkers to creatinine, GFR and albumin excretion rate for early detection of kidney injury, inflammation or endothelial dysfunction and cardiovascular complications in children and adolescents with T1DM or obesity. Children with obesity may have impaired inflammation status, kidney and endothelial function to a higher degree compared to children with T1DM, which may suggest that obesity may impose a greater health burden than T1DM, at least during childhood or the first years after T1DM diagnosis.

Clinical outcomes prediction in kidney transplantation by use of biomarkers from hypothermic machine perfusion.

The clinical outcomes of kidney transplantation from deceased donors have seen significant improvements with the use of machine perfusion (MP), now a standard practice in transplant centers. However, the use of perfusate biomarkers for assessing organ quality remains a subject of debate. Despite this, some centers incorporate them into their decision-making process for donor kidney acceptance. Recent studies have indicated that lactate dehydrogenase (LDH), glutathione S-transferase, interleukin-18, and neutrophil gelatinase-associated lipocalin (NGAL) could predict post-transplant outcomes. Between August 2016 and June 2017, 31 deceased-donor after brain death were included and stroke was the main cause of death. Pediatric patients, hypersensitized recipients were excluded. 43 kidneys were subjected to machine perfusion. Perfusate samples were collected just before the transplantation and stored at -80ºC. Kidney transplant recipients have an average age of 52 years, 34,9% female, with a BMI 24,6±3,7. We employed receiver operating characteristic analysis to investigate associations between these perfusate biomarkers and two key clinical outcomes: delayed graft function and primary non-function. The incidence of delayed graft function was 23.3% and primary non-function was 14%. A strong association was found between NGAL concentration and DGF (AUC=0.766, 95% CI, P=0.012), and between LDH concentration and PNF (AUC=0.84, 95% CI, P=0.027). Other perfusate biomarkers did not show significant correlations with these clinical outcomes. The concentrations of NGAL and LDH during machine perfusion could assist transplant physicians in improving the allocation of donated organs and making challenging decisions regarding organ discarding. Further, larger-scale studies are required.

Impacts of age, type 2 diabetes, and hypertension on circulating neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after prolonged work in the heat in men.

Prolonged work in the heat increases the risk of acute kidney injury (AKI) in young men. Whether aging and age-associated chronic disease may exacerbate the risk of AKI remains unclear. We evaluated plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum kidney injury molecule-1 (KIM1) before and after 180min of moderate-intensity work (200W/m2) in temperate (wet-bulb globe temperature [WBGT] 16°C) and hot (32°C) environments in healthy young (n = 13, 22years) and older men (n = 12, 59years), and older men with type 2 diabetes (T2D; n = 9, 60years) or hypertension (HTN; n = 9, 60years). There were no changes in NGAL or KIM1 concentrations following prolonged work in temperate conditions in any group. Despite a similar work tolerance, the relative change in NGAL was greater in the older group when compared to the young group following exercise in the hot condition (mean difference + 82ng/mL; p < 0.001). Baseline concentrations of KIM1 were ~ 22pg/mL higher in the older relative to young group, increasing by ~ 10pg/mL in each group after exercise in the heat (both p ≤ 0.03). Despite a reduced work tolerance in the heat in older men with T2D (120 ± 40min) and HTN (108 ± 42min), elevations in NGAL and KIM1 were similar to their healthy counterparts. Age may be associated with greater renal stress following prolonged work in the heat. The similar biomarker responses in T2D and HTN compared to healthy older men, alongside reduced exercise tolerance in the heat, suggest these individuals may exhibit greater vulnerability to heat-induced AKI if work is prolonged.

Admission plasma concentration of neutrophil gelatinase-associated lipocalin and -C-reactive protein have additive prognostic value in patients with STEMI

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by Righospitalets Forskningsfond (07IO) Lundbeck Foundation (R186-2015-2132). Background Inflammation plays an apparent critical role in patients with acute coronary syndrome (ACS) and is associated with mortality. However, the complex process is poorly understood. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker originating from mature neutrophils and renal tubular cells. It has previously been shown to be associated with mortality and acute kidney injury in ACS patients. In this study we sought to assess the potential additive prognostic value of NGAL and its relation to other markers of inflammation. Methods In 1556 consecutive ST-elevation myocardial infarction (STEMI) patients, NGAL and C-reactive protein (CRP) plasma concentration were measured at hospital admission, before acute coronary angiography. Patients were stratified to plasma concentration of both biomarkers &amp;gt;/&amp;lt; the median concentration into 4 groups (low NGAL/ low CRP (group 1), low NGAL/high CRP (2), high NGAL/low CRP (3), high NGAL/high CRP(4)). Primary outcome was 30-day all-cause mortality. Results In total, 477 (31%), 324 (21%), 316 (20%), and 439 (28%) patients were stratified in group 1-4, respectively. With 0, 1, or 2 biomarker plasma concentration above the median (group 1 – 4), patients were older (61 – 67 years old, p&amp;lt;0.0001), had more comorbidity (hypertension (40 – 53%), p=0.002; previous stroke (4.0 – 9.9%), p=0.007; peripheral arterial disease (PAD) (2.6 – 10%), p&amp;lt;0.0001; chronic kidney dysfunction (CKD) (0.6 – 11%), p&amp;lt;0.0001) and more critical per-infarction circumstances (time from symptom debut to angiography (170 – 229 minutes), p&amp;lt;0.0001; cardiogenic shock (1.3 – 14%), p&amp;lt;0.0001, cardiac arrest (0.8 – 3.4%), p=0.0002) and lower left ventricular ejection fraction (LVEF) (48 – 43%, p&amp;lt;0.0001). Increased NGAL and CRP was associated with 30-day all-cause mortality (Figure A). Only high NGAL/high CRP was independently associated with 30-day mortality in a cox proportional hazard model when adjusting for age, hypertension, previous stroke, CKD, LVEF, and cardiogenic shock (HR (95% CI) 5.19 (1.20 – 22.52), p=0.03). Both CRP and NGAL had significant predictive value of 30-day mortality (AUC ROC 0.67, p&amp;lt;0.0001 and 0.78, p&amp;lt;0.0001, respectively). Combining NGAL and CRP did, however, not increase the predictive value of NGAL alone (AUC ROC 0.77, p=0.86) (Figure B). Conclusion Combined admission NGAL and CRP plasma concentration was independently associated with 30-day all-cause mortality in STEMI patients. Adding CRP to NGAL did, however, not increase the predictive value.Figure AFigure B

A Pilot Study of the Role of Selected Biomarkers of Kidney Injury in Dogs with Dilated Cardiomyopathy.

Heart and kidney diseases are among the most frequent medical conditions diagnosed in small animals. Due to the functional interconnection between these organs, the concept of the cardio-renal axis has been developed. In this context, renal disease or dysfunction often occurs secondary to heart diseases, such as dilated cardiomyopathy (DCM). DCM is the most common cardiomyopathy and a leading cause of mortality in large-breed dogs. Traditional biomarkers like creatinine or symmetric dimethylarginine concentration are not always effective, especially in the early stages of the disease, underscoring the need for more sensitive markers of renal impairment during heart failure (HF). This study aimed to evaluate the efficacy of selected biomarkers as indicators for early kidney damage in dogs with stage B2 DCM. We measured serum concentrations of cystatin C, KIM-1 (kidney injury molecule-1), and NGAL (neutrophil gelatinase-associated lipocalin) and their ratios to creatinine, analyzing their diagnostic values. Cystatin C was quantified using a sandwich enzyme immunoassay, while KIM-1 and NGAL were measured with enzyme-linked immunosorbent assay kits designed for canine diagnostics. The concentrations were indexed against serum creatinine. The study included 26 dogs: 9 with HF and 17 healthy controls. The mean ± standard deviation for healthy dogs for cystatin C, cystatin C/creatinine ratio, KIM-1, KIM-1/creatinine ratio, NGAL, and NGAL/creatinine ratio were 0.24 ± 0.04, 0.26 ± 0.07, 0.61 ± 0.07, 0.67 ± 0.13, 2.76 ± 1.8, and 2.79 ± 1.81, respectively. For DCM dogs, these values were 0.27 ± 0.1, 0.32 ± 0.12, 0.61 ± 0.08, 0.69 ± 0.17, 6.46 ± 5.22 (p = 0.02), and 7.99 ± 6.53 (p = 0.04). This study's findings suggest that during the asymptomatic phase of DCM, only NGAL concentration and the NGAL/creatinine ratio may serve as diagnostic markers for early-stage kidney injury.

Tissue-resident Lymphocytes Are Released During Hypothermic and Normothermic Machine Perfusion of Human Donor Kidneys.

Machine perfusion is the preferred preservation method for deceased donor kidneys. Perfusate fluid, which contains a complex mixture of components, offers potential insight into the organ's viability and function. This study explored immune cell release, particularly tissue-resident lymphocytes (TRLs), during donor kidney machine perfusion and its correlation with injury markers. Perfusate samples from hypothermic machine perfusion (HMP; n = 26) and normothermic machine perfusion (NMP; n = 16) of human donor kidneys were analyzed for TRLs using flow cytometry. Residency was defined by expressions of CD69, CD103, and CD49as. TRL release was quantified exclusively in NMP. Additionally, levels of cell-free DNA, neutrophil gelatinase-associated lipocalin, and soluble E-cadherin (sE-cadherin) were measured in NMP supernatants with quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Both HMP and NMP samples contained a heterogeneous population of TRLs, including CD4+ tissue-resident memory T cells, CD8+ tissue-resident memory T cells, tissue-resident natural killer cells, tissue-resident natural killer T cells, and helper-like innate lymphoid cells. Median TRL proportions among total CD45+ lymphocytes were 0.89% (NMP) and 0.84% (HMP). TRL quantities in NMP did not correlate with donor characteristics, perfusion parameters, posttransplant outcomes, or cell-free DNA and neutrophil gelatinase-associated lipocalin concentrations. However, CD103+ TRL release positively correlated with the release of sE-cadherin, the ligand for the CD103 integrin. Human donor kidneys release TRLs during both HMP and NMP. The release of CD103+ TRLs was associated with the loss of their ligand sE-cadherin but not with general transplant injury biomarkers.

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

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. Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

Systemic reserve dysfunction and contrast-associated acute kidney injury following percutaneous coronary intervention.

Developing contrast-associated acute kidney injury (CA-AKI) following percutaneous coronary intervention (PCI) is closely related to patient-related risk factors as well as contrast administration. The diagnostic and prognostic roles of neutrophil gelatinase-associated lipocalin (NGAL) in CA-AKI following PCI are not well established. Consecutive patients undergoing PCI were enrolled prospectively. CA-AKI was defined as an increase in the serum creatinine level ≥0.3 mg/dL within 48 hours or ≥1.5 times the baseline within 7 days after PCI. Serum NGAL concentrations were determined immediately before and 6 hours after PCI. The participants were classified into four NGAL groups according to the pre- and post-PCI NGAL values at 75th percentile. CA-AKI occurred in 38 (6.4%) of 590 patients. With chronic kidney disease status (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.06-2.52), NGAL groups defined by the combination of pre- and 6 h post-PCI values were independently associated with the occurrence of CA-AKI (HR 1.69, 95% CI: 1.16-2.45). All-cause mortality for 29-month follow-ups was different among NGAL groups (log-rank p<0.001). Pre-PCI NGAL levels significantly correlated with baseline cardiac, inflammatory, and renal markers. Although post-PCI NGAL levels increased in patients with larger contrast administration, contrast media made a relatively limited contribution to the development of CA-AKI. In patients undergoing PCI, the combination of pre- and post-PCI NGAL values may be a useful adjunct to current risk-stratification of CA-AKI and long-term mortality. CA-AKI is likely caused by systemic reserve deficiency rather than contrast administration itself.

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

We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis. 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. 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. 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.

Plasma Biomarkers Associated to Outcome in Patients with Sars-Cov-2 Infection

Background: A serious consequence of respiratory infections with SARS-CoV-2 is Acute Kidney Injury (AKI). The aim of this study was to evaluate some novel biomarkers measured in plasma for their associations with the outcome of this infection as to AKI and mortality. Methods: Four different HNL (Human Neutrophil Lipocalin) assays were constructed using different antibody configurations, reflecting both neutrophil and epithelial cell activities. TK-1 (Thymidine kinase-1) was measured as a sign of cell destruction and proliferation. For comparison the plasma concentrations of NGAL (Neutrophil Gelatinase Associated Lipocalin), the cytokines IL-6, IL-8 and IFN-γ and of cystatin C, and procalcitonin were also measured. One hundred and three patients with severe respiratory failure admitted to the ICU were sampled for blood at admittance and at day three (n=67) after admittance. Results: Sixty-five percent of the patients developed AKI. The performance of the HNL assay 763/8F was most closely associated to outcome as to AKI and mortality with Area Under the Receiver Operating Characteristics Curve (AUC) of 0.87 and a sensitivity of 80% and a specificity of 88% in COVID-19 patients with and without severe AKI (p&lt;0.0001). TK-1 was significantly related to the development of AKI (p=0.01) and the three cytokines were related to mortality (p=0.004-p&lt;0.001). Conclusion: The HNL variant 763/8F and TK-1 are novel biomarkers that might become useful and novel tools in the management of COVID-19 patients, but likely also in other patients affected by AKI.

Effects of high-intensity intermittent exercise versus moderate-intensity continuous exercise on renal hemodynamics assessed by ultrasound echo.

High-intensity intermittent exercise (HIIE) has become attractive for presenting a variety of exercise conditions. However, the effects of HIIE on renal function and hemodynamics remain unclear. This study aimed to compare the effects of HIIE and moderate-intensity continuous exercise (MICE) on renal hemodynamics, renal function, and kidney injury biomarkers. Ten adult males participated in this study. We allowed the participants to perform HIIE or MICE to consider the impact of exercise on renal hemodynamics under both conditions. Renal hemodynamic assessment and blood sampling were conducted before the exercise (pre) and immediately (post 0), 30 min (post 30), and 60 min (post 60) after the exercise. Urine sampling was conducted in the pre, post 0, and post 60 phases. There was no condition-by-time interaction (p = 0.614), condition (p = 0.422), or time effect (p = 0.114) regarding renal blood flow. Creatinine-corrected urinary neutrophil gelatinase-associated lipocalin concentrations increased at post 60 (p = 0.017), but none exceeded the cut-off values for defining kidney injury. Moreover, there were no significant changes in other kidney injury biomarkers at any point. These findings suggest that high-intensity exercise can be performed without decreased RBF or increased kidney injury risk when conducted intermittently for short periods.

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory markers in schizophrenia: A comparative analysis of drug-naive schizophrenia patients, remitted patients, and healthy controls

This study aims to examine the plasma concentrations of NGAL and other inflammatory parameters, including TNF-α, IL-1β, and IFN-γ, in schizophrenia patients and healthy volunteers. It also investigates potential associations between these biomarkers and symptom severity in schizophrenia and the utility of NGAL as a potential diagnostic and monitoring biomarker for schizophrenia. The study included 49 drug-naive schizophrenia patients (DNS), 59 patients with schizophrenia in remission (REM) on antipsychotic treatment, and 58 healthy volunteers (HC). The Positive and Negative Symptoms Evaluation Scale (PANSS) was utilized to assess the severity of symptoms in schizophrenia patients. Plasma levels of TNF-α, IL-1β, IFN-γ, and NGAL were measured for all participants. NGAL levels were significantly lower in the DNS group than in HC. Significantly lower TNF-α levels were observed in both the DNS and REM groups compared to the HC group. Notably, a statistically significant positive correlation was detected between TNF-α and NGAL levels. The findings of this study are noteworthy, as they demonstrate that drug-naive individuals with schizophrenia exhibit significantly diminished levels of NGAL and TNF-α compared to healthy controls. These identified biomarkers hold promise for providing valuable insights into the complex and evolving pathophysiology of schizophrenia.

KIM-1, IL-18, and NGAL, in the Machine Learning Prediction of Kidney Injury among Children Undergoing Hematopoietic Stem Cell Transplantation-A Pilot Study.

Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.

Hypohydration induced by prolonged cycling in the heat increases biomarkers of renal injury in males

PurposeRecent studies have shown that hypohydration can increase renal injury. However, the contribution of hypohydration to the extent of renal injury is often confounded by exercise induced muscle damage. Therefore, the aim of the present study was to investigate the effect of manipulating hydration status during moderate-intensity cycling in the heat on biomarkers of renal injury.MethodsFollowing familiarisation, fourteen active males (age: 21 [20–22] y; BMI: 22.1 ± 1.9 kg/m2; V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\dot{V} $$\\end{document}O2peak: 55 ± 9 mL/kg/min) completed two experimental trials, in a randomised cross-over design. Experimental trials consisted of up to 120 min of intermittent cycling (~ 50% Wpeak) in the heat (~ 35 °C, ~ 50% relative humidity). During exercise, subjects consumed either a water volume equal to 100% body mass losses (EU) or minimal water (HYP; 75–100 mL) to induce ~ 3% body mass loss. Blood and urine samples were collected at baseline, 30 min post-exercise and 24 h post-baseline, with an additional urine sample collected immediately post-exercise.ResultsThirty minutes post-exercise, body mass and plasma volume were lower in HYP than EU (P < 0.001), whereas serum and urine osmolality (P < 0.001), osmolality-corrected urinary kidney injury molecule-1 concentrations (HYP: 2.74 [1.87–5.44] ng/mOsm, EU: 1.15 [0.84–2.37] ng/mOsm; P = 0.024), and percentage change in osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (HYP: 61 [17–141] %, EU: 7.1 [– 4 to 24] %; P = 0.033) were greater in HYP than EU.ConclusionHypohydration produced by cycling in the heat increased renal tubular injury, compared to maintaining euhydration with water ingestion.

Interaction between serum neutrophil gelatinase associated lipocalin and visceral fat area on cardiovascular health in a cohort of community-based individuals

BackgroundWe assessed the predictive values of neutrophil gelatinase-associated lipocalin (NGAL), fat distribution, and their interaction on the development of major adverse cardiovascular events (MACE) in a community-based cohort of middle-aged and older individuals. MethodsThis prospective study involved 1349 adults (43.2% men) aged 50–80 y, without baseline cardiovascular diseases, from communities in 2013–2014. All participants were followed up for a mean of 7.6 y via phone calls and medical records. Serum NGAL concentrations were analyzed at baseline. Fat distribution, including subcutaneous fat area and visceral fat area (VFA), was assessed by magnetic resonance imaging. ResultsIn fully-adjusted Cox regression models, baseline high NGAL concentrations were related to an increased risk of MACE in women [HR 1.75, 95% CI 1.03–2.99], compared with low NGAL concentrations. After stratification by VFA concentrations, the observed association was more predominant in women with baseline low VFA (HR 1.24, 95% CI 1.11–1.38). Moreover, the association between NGAL and MACE was interacted by VFA, strengthening the association at low VFA concentrations (Pinteraction < 0.05). ConclusionsSerum NGAL determined at baseline predicts the development of MACE, and the association is modified by VFA in women.

The Urinary Concentrations of Neutrophil Gelatinase-Associated Lipocalin, Cystatin C and Osteopontin in the Healthy Term and Stable Preterm Neonates: A Pilot Study.

In neonates, the assessment of kidney function with serum creatinine is limited; therefore, more effective biomarkers are needed. The study aimed at analyzing the concentrations of renal biomarkers (osteopontin, cystatin C, and NGAL) in neonates. The study included 80 term and 20 preterm neonates aged 28-33 weeks of gestation. Biomarkers were measured in urine. Term neonates' urine was collected on the 1st day of life. Preterm neonates' urine was collected on the 1st, 8th, 15th, 22nd day of life. Biomarkers' concentrations were normalized to urinary creatinine (cr.) and presented as urinary biomarker/cr. ratios. Median values of biomarker/creatine ratios in term and preterm neonates were the following: cystatin C/cr.: 7.26 and 439.49; osteopontin/cr.: 135.86 and 1633.37; NGAL/cr. in girls: 212.14 and 256.93; and NGAL/cr. in boys 27.123 and 65.29 ng/mg cr. In preterm neonates the cystatin C/cr. ratio was higher on the 1st than on the 8th day. The osteopontin/cr. ratio did not differ between the days. The NGAL/cr. ratio in girls was higher on the 8th than on the 22nd day, and in boys, the lowest was on the 22nd day. Prematurity in stable, Caucasian neonates might cause higher osteopontin and cystatin C excretion, but not NGAL. The excretion of NGAL and cystatin C, but not osteopontin, may change during first weeks of premature neonate's life.

THU339 Neutrophil Gelatinase-associated Lipocalin And B2-microglobulin May Reflect Early Diabetic Nephropathy In Asymptomatic Patients With Type 1 Diabetes

Abstract Disclosure: N. Papadopoulou: None. M. Arkoumani: None. I. Papassotiriou: None. A. Mantzou: None. G.P. Chrousos: None. N. Tentolouris: None. C. Kanaka-Gantenbein: None. Type 1 diabetes (T1D) is a frequent autoimmune disease in childhood, adolescence and young adulthood and may cause microvascular complications. Several studies have shown that increased serum or urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and beta 2 microglobulin (b2-microglobulin) are associated with microvascular complications like nephropathy. Hypothesis and Underlying Question the Research Addresses: We assessed the role of serum and urine NGAL and b2-microglobulin, biomarkers of renal dysfunction, in unravelling early renal dysfunction in T1D. Overview of Experimental Design and Methodology: Two patient groups who took part in two-centers’ prospective cohorts were studied. Sixty-one patients with T1D, aged 5-17 years from the Diabetes Center of Aghia Sophia Children’s Hospital, University of Athens, Greece, and 34 patients with T1D aged 18-44 years from the Diabetes Center, 1st Propaedeutic Department Laiko of the Laikon University Hospital of Athens, Greece were recruited. Sixty age- and sex-matched apparently healthy controls were also included in the study . Along with standard blood and urine chemistry, serum and urine NGAL concentrations and serum b2-microglobulin were determined by means of immunoenzymatic techniques. Estimated glomerular filtration rate (eGFR) was calculated with CKD EPI. Both physical and laboratory examinations were obtained in 2 time-points, at baseline and 12 months later. Main Results: In both young and adult groups with T1D, urine NGAL correlated positively with microalbuminuria (r=0.33, p=0.003) and decreased eGFR (r= -0.37, p=0.0008) irrespectively of gender or age. Decreased values of eGFR were correlated with increased values of b2-microglobulin (r= -0.30, p=0.002). Interpretation of Results and Conclusions: Urine NGAL as well as serum b2-microglobulin levels, proposed biomarkers of renal dysfunction, correlated with indices of early diabetic nephropathy, characterized by both microalbuminuria and decreased eGFR in patients with T1D, showing similar results in a broad patients’ age range. Thus, this marker may unmask early reversible renal dysfunction before overt nephropathy appears. However, prior to its clinical application, this biomarker must undergo thorough validation in several cohorts. Presentation: Thursday, June 15, 2023

Diagnostic value of cerebrospinal fluid Neutrophil Gelatinase-Associated Lipocalin for differentiation of bacterial meningitis from tuberculous meningitis or cryptococcal meningitis: a prospective cohort study

BackgroundThe early differential diagnosis between bacterial meningitis (BM) and tuberculous meningitis (TBM) or cryptococcal meningitis (CM) remains a significant clinical challenge. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been reported as a novel inflammatory biomarker in the early stages of infection. This study aimed to investigate whether cerebrospinal fluid (CSF) NGAL can serve as a potential biomarker for distinguishing between BM and TBM or CM.MethodsWe prospectively enrolled the patients with suspected CNS infections at admission and divided them into three case groups: BM (n = 67), TBM (n = 55), CM (n = 51), and an age- and sex-matched hospitalized control (HC, n = 58). Detected the CSF NGAL and assessed its diagnostic accuracy in distinguishing between BM and TBM or CM. Additionally, longitudinally measured the CSF NGAL levels in patients with BM to evaluate its potential as a monitoring tool for antibacterial treatment.ResultsThe concentration of CSF NGAL in BM was significantly higher than in TBM, CM, and HC (all P < 0.05), while the serum NGAL did not show significant differences among the three case groups. The ROC analysis demonstrated that CSF NGAL presented a good diagnostic performance with an AUC of 0.834 (0.770–0.886) and at the optimal cutoff value of 74.27 ng/mL with 70.15% sensitivity and 77.36% specificity for discriminating BM with TBM and CM. Additionally, the CSF NGAL in the convalescent period of BM was significantly lower than in the acute period (P < 0.05).ConclusionsCSF NGAL may serve as a potential biomarker for distinguishing between acute BM and TBM or CM. Additionally, it holds clinical significance in monitoring the effectiveness of antibiotic therapy for BM.

Negative symptoms and neurocognition in drug-naïve schizophrenia: moderating role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and interferon-gamma (INF-γ).

Previous studies reported that peripheral inflammation was associated with cognitive performance and brain structure in schizophrenia. However, the moderating effect of inflammation has not been extensively studied. This study investigated whether inflammation markers moderated the association between negative symptoms and neurocognition in schizophrenia. This cross-sectional study included 137 drug-naïve schizophrenia patients (DNS) and 67 healthy controls (HC). We performed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for cognitive assessment and the Positive and Negative Syndrome Scale (PANSS) for psychiatric symptoms. Plasma concentrations of interferon-gamma (IFN-γ), neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor kappa B (NF-κB) were measured. The MCCB neurocognition score, social cognition score, and total score; the plasma concentrations of NGAL, IFN-γ, and NF-κB were significantly decreased in DNS than in HC (all P's < 0.001). PANSS negative subscale (PNS), PANSS reduced expressive subdomain (RES) negatively correlated with neurocognition score (P = 0.007; P = 0.011, respectively). Plasma concentrations of IFN-γ and NGAL positively correlated with neurocognition score (P = 0.043; P = 0.008, relatively). The interactions of PNS × NGAL; PNS × IFN-γ; RES × IFN-γ accounted for significant neurocognition variance (P = 0.025; P = 0.029, P = 0.007, respectively). Simple slope analysis showed that all the above moderating effects only occurred in patients with near normal IFN-γ and NGAL levels. Plasma concentrations of IFN-γ and NGAL moderated the relationship between negative symptoms (especially RES) and neurocognition in schizophrenia. Treatment targeting inflammation may contribute to neurocognition improvement in schizophrenia.