Neutrophil Gelatinase-associated Lipocalin Concentrations Research Articles

Plasma Neutrophil Gelatinase-Associated Lipocalin Associates with New-Onset Chronic Kidney Disease in the General Population.

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.

Acute Kidney Injury Is Associated with Higher Serum Cys-C and NGAL Concentrations, and Risk of Mortality in Premature Calves with Respiratory Distress Syndrome.

The purpose of the present study was to establish the development of acute kidney injury (AKI) and evaluate the usefulness of kidney-specific biomarkers in diagnosing AKI in premature calves with respiratory distress syndrome (RDS). Ten-term healthy and 70 premature calves with RDS were enrolled. Clinical examination, blood gases, and chemical analysis were performed at admission and 72 h. Serum concentrations of blood urea nitrogen (BUN), creatinine (Cre), phosphorus (P), cystatin-C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (UMOD), and liver-type fatty acid-binding protein (L-FABP) were measured to evaluate kidney injury. Our findings showed that 38.5% of the premature calves with RDS developed AKI. The RDS-AKI group had a 4-fold higher mortality risk than the RDS-non-AKI group. Cys-C, with 90% and 89% specificity, and NGAL, with 100% sensitivity and 85% specificity, were the most reliable biomarkers to determine AKI in premature calves. The usefulness of any biomarker to predict mortality was not found to be convincing. In conclusion, AKI can develop as a consequence of hypoxia in premature calves and may increase the risk of mortality. In addition, serum Cys-C and NGAL concentrations may be useful in the diagnosis of AKI in premature calves with RDS.

Relationship between neutrophil gelatinase-associated lipocalin levels and disease parameters including clinicopathological parameters and various cytokine levels in systemic lupus erythematosus.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury and indicates tubular damage. Lupus nephritis-associated renal injury is characterized by damage to the glomeruli and tubular portions of the kidneys. Therefore, NGAL concentrations are expected to vary according to the severity of systemic lupus erythematosus (SLE). In this study, samples from (NZB × NZW) F1 mice at an advanced stage of SLE were used to determine whether serum and urine NGAL concentrations or the urine NGAL:creatinine (uNGAL/C) ratio can be used to reflect diet, disease state, and treatment efficacy. Additionally, the relationship between the levels of NGAL and various cytokines in the serum in SLE was evaluated. Mice were divided into the following four groups (n=15): CN, chow diet and no treatment (saline; intraperitonially injected [i.p.]; 200 μL/day); CP, chow diet and methylprednisolone (i.p.; 5 mg/kg/day); HN, high-fat diet and no treatment (saline [i.p.]; 200 μL/day); and HP, high-fat diet and methylprednisolone treatment (i.p.; 5 mg/kg/day) every day from 6 to 42 weeks of age. The serum and urine NGAL levels and uNGAL/C values were significantly lower in the CP group than those in the CN group. Further, serum NGAL concentration demonstrated a strong positive correlation with urine NGAL levels, uNGAL/C, urine protein concentrations, urine protein:creatinine ratio, and the expression of several cytokines associated with SLE pathogenesis (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and interferon-induced protein [IP]-10). These results suggest that NGAL has a strong positive correlation with the clinicopathological parameters and several key cytokines in SLE.

Could melatonin prevent Vancomycin-induced nephrotoxicity in critically ill patients? A randomized, double-blinded controlled trial.

Previous research showed some clinical benefits regarding the nephroprotective effect of melatonin. So, this study aimed to evaluate the beneficial effect of oral melatonin on preventing acute kidney injury (AKI) in patients who received vancomycin therapy in the intensive care unit (ICU). We performed a randomized, double-blinded, placebo-controlled pilot study in an academic hospital. Adult patients admitted to the ICU who received vancomycin with normal gastrointestinal and kidney function were randomized into treatment or placebo groups. After that, enrolled patients received a tablet of melatonin (3 mg) or placebo twice daily for seven consecutive days. The occurrence of AKI was assessed by RIFLE criteria (by measurement of serum creatinine (SCr)) and plasma neutrophil gelatinase-associated lipocalin (NGAL) concentration. Moreover, other data related to renal functions and SOFA were also compared between groups. A total of 90 patients were included in the study, while 21patients in the placebo group and 20 in the intervention group completed the study. There were no significant differences between groups regarding baseline SCr, BUN, urine output, NGAL, SOFA, and glomerular filtration rate (GFR). Our results showed that these differences remained insignificant after a 7-day follow-up between groups. However, the incidence of AKI was significantly lower in the melatonin group based on the NGAL cutoff (> 150 ng/mL). We detected a significant decrease in vancomycin-induced nephrotoxicity incidence in patients receiving melatonin compared to placebo. However, more clinical trials in a larger population were required to confirm this result.

Lipid metabolism and renal function markers in obese adolescents.

To investigate the relationship of renal function markers and lipid metabolism parameters in obese adolescents. The study comprised 76 children aged 11-17 years, hospitalised due to: obesity (group I - 19 children) or obesity accompanied by obesity-induced hypertension (group II - 30 children) or normosthenic children with a diagnosed tension headaches (control group - 27 children). A subgroup with metabolic syndrome (MS - 16 children) was also separated. Renal function was assessed on the basis of: serum creatinine concentration, glomerular filtration rate estimated using Schwartz eqation (eGFR), determination of plasma and urinary neutrophil gelatinase-associated lipocalin and cystatin C. On the basis of statistical analysis, it was checked whether renal function markers depend on lipid metabolism parameters. In the study groups mean creatinine concentrations were significantly higher and eGFR values significantly lower than in the control group, but they remained within norm. Differences in plasma and urinary neutrophil gelatinase-associated lipocalin concentrations were not significant. Mean cystatin C concentrations were significantly higher in the group of obese children. Multiple linear regression analysis showed that the most important predictor was: LDL-C for urinary neutrophil gelatinase-associated lipocalin (R2 = 0.42) and TG for eGFR (R2 = 0.44) concentrations in group I; cholesterol for creatinine concentrations in MS group (R2 = 0.44). Renal function of the obese adolescents included in the study was normal and the associations with lipid metabolism were poorly expressed.

Neutrophil Gelatinase-Associated Lipocalin in Synovial Fluid from Horses with and without Septic Arthritis

Neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to be a highly sensitive and specific marker of joint infection in humans. The aim of the study was to investigate NGAL concentrations in synovial fluid (SF) from horses with septic synovitis, horses without septic synovitis, and horses with uncertain status. NGAL was measured in 177 admission samples obtained from 152 horses. From a subset of horses (n = 35), additional samples obtained sequentially over the course of treatment were available. Concentrations of NGAL were significantly higher in septic synovitis (n = 47 samples) than in samples classified as non-septic (n = 103) or samples with uncertain status (n = 27), with median NGAL concentrations in the three groups being 1236, 16.8, and 266.4 µg/L, respectively. NGAL discriminated nearly perfectly between septic and non-septic (area under the receiver operating characteristic curve 0.98, 95% confidence interval 0.95-1.00). The optimal cut-off value for maximal sensitivity (87.2%) and specificity (75.0%) to discriminate septic samples from those with uncertain status was 444.6 µg/L, with an area under the receiver operating characteristic curve of 0.85 (95% confidence interval 0.74-0.93). Concentrations declined over time in horses undergoing treatment. NGAL is a novel biomarker that seems to have great potential for identifying septic synovitis and for monitoring the response to treatment of synovial infection in horses.

Serum procalcitonin, C-reactive protein, and neutrophil gelatinase-associated lipocalin in early diagnosis of acute kidney injury after upper urinary tract calculi.

To investigate the value of serum procalcitonin(PCT), C-reactive protein(CRP), and neutrophil gelatinase-associated lipocalin(NGAL) in the early diagnosis of acute kidney injury(AKI) after upper urinary tract calculi(UUTC). The clinical data of 86 patients who underwent UUTC surgery in our hospital from March 2020 to April 2021 were analyzed retrospectively(Approval number: 20211205L, Date: 2021-12-21). Patients were divided into an AKI group (AKI≥7 days after the operation) and a Non-AKI group. PCT, CRP, and NGAL concentrations were compared before and two hours after the operation. Multivariate logistic regression analysis was used to identify risk factors affecting the early occurrence of AKI post-operation. The receiver operating characteristic curve evaluated PCT, CRP, and NGAL in the early AKI diagnosis. A total of 86 patients (30 with AKI and 56 with Non-AKI) were included. Kidney injury molecule-1(KIM-1) and urinary microalbumin(mAlb) concentrations were significantly higher in the AKI group (P<0.05). PCT, CRP, and NGAL concentrations were significantly higher two hours after the operation than before the operation (P<0.05). KIM-1 levels and elevated PCT, CRP and NGAL concentrations affected the establishment of AKI after UUTC. The sensitivity of PCT, CRP, and NGAL in evaluating AKI after UUTC were 81.17%, 84.42%, and 79.02%; the specificity was 62.31%, 71.48%, and 73.32%; and the AUC was 0.812, 0.885 and 0.804 respectively. PCT, CRP, and NGAL concentrations in patients with AKI after UUTC were significantly increased two hours after the operation, which can be used for the early diagnosis of AKI after UUTC operation.

Heat stress and incidence of acute kidney injury among agricultural workers in Spain

BackgroundHeat stress is associated with adverse health outcomes among workers, including acute kidney injury. We aimed to estimate the incidence of acute kidney injury over the course of the work shift and the association with heat stress among agricultural workers in Spain, where summer temperatures are high and heatwaves are expected to be frequent. MethodsMale agricultural workers were enrolled in two different harvesting seasons and provinces, as follows: summer in Alacant (n=43; September, 2018) and winter in Tarragona (n=52; November, 2018, and January, 2019). For each participant, we estimated exposure to heat stress during a work shift based on the wet bulb globe temperature (WBGT) index and acute kidney injury cross-shift incidence, defined as an increase in post-shift serum creatinine by at least 0·3 mg/dL or at least 1·5 times the pre-shift serum creatinine concentration. We collected information on confounders. For a subsample of participants (n=54), we measured neutrophil gelatinase-associated lipocalin (NGAL) concentrations before and after the working shift. We used regression models to assess if heat stress was a risk factor for acute kidney injury and increase in NGAL concentrations. FindingsThe mean WBGT was 24·5°C (SD 2·0; range 20·2–27·1) during the summer season and 14·2°C (8·0–20·7) during the winter season. Nine (21%) of 43 workers harvesting during summer were exposed to heat stress. Incidence of acute kidney injury was higher during the summer season (14 [33%] of 43 workers vs two [4%] of 52 workers). Heat stress was associated with cross-shift incidence of acute kidney injury (age-adjusted odds ratio 9·6, 95% CI 1·4–67·9). No differences in NGAL concentrations were observed between participants exposed to heat stress. InterpretationHeat stress is a risk factor for acute kidney injury among agricultural workers in Spain, even when environmental temperatures are not extreme. Monitoring acute kidney injury incidence among agricultural workers in Spain is important in the context of climate change, as frequent episodes of acute kidney injury can lead to chronic kidney disease. FundingCarlos III Health Institute and European Union.

Urinary NGAL, IGFBP-7, and TIMP-2: novel biomarkers to predict contrast medium-induced acute kidney injury in children

Background Serum creatinine (SCr) is unreliable in detecting acute changes in kidney function. Early recognition of contrast-induced acute kidney injury (CI-AKI) can provide better opportunities for preventive interventions. Therefore, the purpose of this study is to examine the value of the combined detection of urinary neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor binding protein-7 (IGFBP-7), and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the early diagnosis of children with CI-AKI. Methods A prospective, single-center clinical trial was performed and included 172 children aged 0–18 years. The dynamic changes of urinary NGAL, IGFBP-7, and TIMP-2 levels in children with intravascular injection of contrast medium were investigated to determine whether they can diagnose CI-AKI early. Results CI-AKI occurred in 20 of 137 enrolled patients, and the incidence was 14.59%. In the CI-AKI group, urinary levels of NGAL, IGFBP-7, TIMP-2, and [IGFBP-7]*[TIMP-2] were significantly increased 2 h after angiography and remained at high levels at 6 h. Using a cutoff value of 36.274 ng/mL, the specificity was 70.0%, and the sensitivity was 68.4% for the prediction of CI-AKI, which was excellent for urinary NGAL. When both urinary IGFBP-7 and TIMP-2 were used together, urinary [IGFBP-7]*[TIMP-2] at 0.417(ng/mL)2/1000 was regarded as the cutoff value. The specificity was 80.0%, and the sensitivity was 81.2%. Conclusions NGAL, IGFBP-7, and TIMP-2 concentrations in the urine of children after receiving injections of contrast medium increased faster than SCr and had good clinical value for the early diagnosis of CI-AKI in children. The combination of IGFBP-7 and TIMP-2 was better than either analyte alone.

The Effect of a Comprehensive Life-Style Intervention Program of Diet and Exercise on Four Bone-Derived Proteins, FGF-23, Osteopontin, NGAL and Sclerostin, in Overweight or Obese Children and Adolescents.

The adipose and bone tissues demonstrate considerable interconnected endocrine function. In the present study, we determined the concentrations of fibroblast growth factor-23 (FGF-23), osteopontin, neutrophil gelatinase-associated lipocalin (NGAL) and sclerostin in 345 children and adolescents who were overweight or obese (mean age ± SD mean: 10.36 ± 0.16 years; 172 males, 173 females; 181 prepubertal; and 164 pubertal) before and after their participation in a comprehensive life-style intervention program of diet and exercise for one year. Following the one-year life-style interventions, there was a significant decrease in BMI (p < 0.01), FGF-23 (p < 0.05), osteopontin (p < 0.01) and NGAL (p < 0.01), and an increase in sclerostin (p < 0.01) concentrations. BMI z-score (b = 0.242, p < 0.05) and fat mass (b = 0.431, p < 0.05) were the best positive predictors and waist-to-height ratio (WHtR) (b = −0.344, p < 0.05) was the best negative predictor of the change of osteopontin. NGAL concentrations correlated positively with HbA1C (b = 0.326, p < 0.05), WHtR (b = 0.439, p < 0.05) and HOMA-IR (b = 0.401, p < 0.05), while BMI (b = 0.264, p < 0.05), fat mass (b = 1.207, p < 0.05), HDL (b = 0.359, p < 0.05) and waist circumference (b = 0.263, p < 0.05) were the best positive predictors of NGAL. These results indicate that FGF-23, osteopontin, NGAL and sclerostin are associated with being overweight or obese and are altered in relation to alterations in BMI. They also indicate a crosstalk between adipose tissue and bone tissue and may play a role as potential biomarkers of glucose metabolism. Further studies are required to delineate the physiological mechanisms underlying this association in children and adolescents.

Bicistronic vector-based procedure to measure correlative expression and bacteriostatic activity of recombinant neutrophil gelatinase-associated lipocalin

Neutrophil gelatinase-associated lipocalin (NGAL) is a component of the human innate immune system that exerts bacteriostatic effects. Recent research suggests that NGAL is also a promising biomarker for tubular damage and aids in the early diagnosis of acute kidney injury. Therefore, the development of a method to efficiently produce recombinant NGAL has considerable clinical value. This study aimed to analyze the correlation between fluorescence reporter (enhanced green fluorescent protein, EGFP) intensity and NGAL levels, mediated by a bicistronic expression system based on internal ribosome entry sites (IRESs). During the 14-day culture period, EGFP intensity was positively correlated with NGAL concentrations. The purified protein also exerted bacteriostatic effects, interfering with bacterial iron uptake machinery during periods of iron starvation. The purified NGAL was also applied to generate a standard curve that could be used for enzyme-linked immunosorbent assay of samples containing unknown NGAL quantities. In conclusion, we successfully developed a procedure using EGFP and IRES-based vector to predict NGAL production levels and optimize protein harvest time. Our approach is also a simple and effective method for evaluating bioactivity.

Serum neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic tool in pediatric acute appendicitis: a prospective validation study

IntroductionNGAL has recently been studied as a biomarker in the diagnostic context of pediatric acute appendicitis (PAA), although existing series are scarce and have limited sample sizes.Materials and methodsA prospective observational study was designed to validate serum NGAL as a diagnostic tool in PAA. This study included 215 patients, divided into 3 groups: (1) patients undergoing major outpatient surgery (n = 63), (2) patients with non-surgical abdominal pain in whom a diagnosis of PAA was excluded (n = 53) and (3) patients with a confirmed diagnosis of PAA (n = 99). Patients in group 3 were divided into complicated or uncomplicated appendicitis. In 201 patients, a serum sample was obtained at the time of diagnosis and NGAL concentration was determined by ELISA. The Kolmogorov–Smirnov test was used to assess normality. Comparative statistical analyses were performed using the Mann–Whitney U test, the Kruskal-Wallis test and the Fisher’s exact test. To calculate the discriminative ability of the molecule, the area under the receiver-operating characteristic curves (AUC) was calculated. A p value < 0.05 established statistical significance.ResultsMedian (interquartile range) of serum NGAL values were 38.88 (27.15–48.04) ng/mL (group 1), 51.84 (37.33–69.80) ng/mL (group 2) and 65.06 (50.50–86.60) ng/mL (group 3). The AUC (group 2 vs 3) was 0.642 (95% CI 0.542–0.741) (p < 0.001) and the best cutoff point was found to be at 40.97 ng/mL, with a sensitivity of 89% and a specificity of 34.6%. No statistically significant differences in serum NGAL values were found between patients with uncomplicated PAA and those with complicated PAA.ConclusionsThis prospective validation study with a large sample size confirms that the diagnostic yield of NGAL in the context of PAA is only moderate, and therefore, it should not be used as a unique diagnostic tool. Furthermore, NGAL is not a valid biomarker to discern between uncomplicated and complicated PAA.

Urinary biomarkers of kidney injury in patients treated with anti-VEGF drugs

Antiangiogenic drugs are widely used in oncological practice and are aimed at inhibiting angiogenesis. Despite the high antitumor efficacy, their use may be limited by nephrotoxicity, and therefore the search for early biomarkers of kidney damage remains relevant, which will preserve a favorable safety profile of therapy. To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs. The study included patients (n=50) who received intravenous anti-VEGF drugs (aflibercept, bevacizumab, ramucirumab) in various chemotherapy regimens. Concentrations of tubular damage markers KIM-1 (Kidney Injury Molecule-1) and NGAL (Neutrophil Gelatinase-Associated Lipocalin), hypoxia marker HIF-1 (Hypoxia-Inducible Factor 1-alpha) in urine samples were determined by enzyme-linked immunosorbent assay (ELISA) before treatment, and during 8 weeks of treatment. To assess the risk factors for kidney damage, a logistic regression analysis was performed with the inclusion of the main clinical and laboratory parameters. A decrease in the calculated GFR of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) of less than 60 ml/min per 1.73 m2 at week 8 of treatment was noted in 42% of patients. An increase in NGAL, KIM-1, HIF-1 and nephrin in urine during the first two weeks of therapy predicted the development of renal damage by the 8th week of follow-up. When constructing ROC-curves, the high sensitivity and specificity of these urinary indicators as prognostic markers were established. Among the clinical and laboratory indicators, independent unfavorable prognostic factors of nephrotoxicity were an initial decrease in eGFR, a history of hypertension, an increase in the concentration of KIM-1 and HIF-1 in urine during the first two weeks of therapy. The predictors of renal damage in the treatment with antiangiogenic drugs were previously an increase in NGAL, KIM-1 and HIF-1 in urine during the first two weeks after the start of therapy.

Enhanced Detection of Cardiac Surgery-Associated Acute Kidney Injury by a Composite Biomarker Panel in Patients with Normal Preoperative Kidney Function.

We have recently shown that minor subclinical creatinine dynamic changes enable the excellent detection of acute kidney injury (AKI) within 6–12 h after cardiac surgery. The aim of the present study was to examine a combination of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine for enhanced AKI detection early after cardiac surgery. Elective patients with normal renal function undergoing cardiac surgery using cardiopulmonary bypass were enrolled. Concentrations of plasma NGAL, serum CysC and serum creatinine were determined after the induction of general anesthesia, at the termination of the cardiopulmonary bypass and 2 h thereafter. Out of 119 enrolled patients, 51 (43%) developed AKI. A model utilizing an NGAL, CysC and creatinine triple biomarker panel including sequential relative changes provides a better prediction of cardiac surgery-associated acute kidney injury than any biomarker alone already 2 h after the termination of the cardiopulmonary bypass. The area under the receiver-operator curve was 0.77, sensitivity 77% and specificity 68%.

Concentrations of neutrophil gelatinase-associated lipocalin are increased in serum and peritoneal fluid from horses with inflammatory abdominal disease and non-strangulating intestinal infarctions.

Neutrophil gelatinase-associated lipocalin (NGAL) is produced in response to inflammation in horses, but it has not yet been investigated as a biomarker in horses with the abdominal disease. To investigate NGAL in serum and peritoneal fluid in horses with the abdominal disease. Retrospective clinical study. Data from medical records of 270 horses admitted with acute abdominal disease (simple obstructions [n=43], strangulating obstructions [n=104], inflammatory abdominal disease [n=99], non-strangulating intestinal infarction [NSII, n=24]) and 9 healthy control horses were reviewed, and serum and peritoneal fluid samples were retrieved from a biobank. NGAL was measured in serum and peritoneal fluid by ELISA. Differences in NGAL concentrations between groups were assessed. Healthy horses had low serum and peritoneal fluid concentrations of NGAL (median=21.0 and 9.5μg/L, respectively). Neither serum nor peritoneal fluid NGAL concentrations (median serum, peritoneal fluid) differed between healthy horses and horses with simple (28.1μg/L, 13.0μg/L) and strangulating intestinal obstructions (34.7μg/L, 38.4μg/L). Horses with NSII (308.0μg/L, 2163.0μg/L) and inflammatory abdominal disease (171.1μg/L, 314.1μg/L) had higher serum and peritoneal fluid concentrations of NGAL than the other groups (p < 0.001). Peritoneal fluid NGAL concentrations in horses with NSII were higher than in horses with inflammatory abdominal disease (p= 0.03). Retrospective study design; small group of control horses. NGAL is a marker of inflammation in horses with the abdominal disease. The high peritoneal fluid concentration of NGAL in horses with NSII compared to all other groups may render NGAL useful for identifying this condition, which is otherwise difficult to differentiate from other types of peritonitis. Thereby, NGAL may potentially facilitate timely surgical intervention in this group of patients. The results of this study must be evaluated in larger, and preferably prospective, studies to obtain a more comprehensive evaluation of the diagnostic utility of NGAL.

Electrochemical detection of acute renal disease biomarker by Galinstan nanoparticles interfaced to bilayer polymeric structured dirhenium heptoxide film

This work describes a facile fabrication of an efficient electrochemical sensor utilizing sonication-derived Galinstan nanoparticles (Galinstan NPs) interfaced to annealed dirhenium heptoxide (Re2O7) thin-film on Silicon (Si) for the quantitative detection of the most promising acute renal disease biomarker Neutrophil Gelatinase Associated Lipocalin (NGAL). Under optimized preconditions, the anti-NGAL antibodies were immobilized on the Galinstan NPs/Re2O7/Si electrode by carbodiimide crosslinking to detect NGAL. The composition, morphology, and structural properties of the electrode were elucidated by various physical characterizations. The sensor obtained a high sensitivity (0.018 µA-1ng-1ml−1, R2 = 0.99) in differential pulse voltammetry and a minimum detection limit (2.14 ng ml−1) in electrochemical impedance spectroscopy for a wide range of NGAL concentrations (25–650 ng ml−1) with high selectivity and stability. The intensified performance of the sensor was achieved by the summed-up electron transfer from the Re2O7 film to Galinstan NPs and Galinstan NPs to the electroactive reactants. Additionally, the outer 2D gallium oxide (Ga2O3) layer of Galinstan Nps enhanced the redox activities, whereas the metallic core contributed to the magnificent conductivity. The excellent recovery rates of the sensor for different concentrations of NGAL measured in commercial human serum by the standard addition method assured the feasibility of the sensor.

Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI.

Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1β (IL-1β), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1–13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy.

Relationship between Neutrophil Gelatinase-Associated Lipocalin, Eosinophil Cationic Protein, Cytokines, and Atopic Sensitization in Patients with Allergic Diseases.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on eosinophil activation, atopic sensitization, and systemic inflammation in allergic diseases has rarely been investigated. This study aimed to investigate the relationship between NGAL, eosinophil cationic protein (ECP), cytokines, and allergen-specific immunoglobulin E (sIgE) in allergic diseases. A total of 136 patients with allergies and 58 healthy individuals were evaluated. The concentrations of NGAL, ECP, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), sIgE, total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) were measured. The transforming growth factor-β1 (TGF-β1) level was measured as a profibrotic marker of bronchial asthma. Allergic patients had significantly higher NGAL, ECP, and hsCRP levels than healthy individuals. However, there was no significant difference in NGAL levels between patients with positive and negative ECP tests and those with high and low sIgE scores. Asthmatic patients with elevated NGAL exhibited a significantly higher TGF-β1 level than those without elevated NGAL. However, no significant difference was observed in the ECP, IL-5, and sIgE levels between the two groups. Among the patients with a positive ECP test, subjects with elevated hsCRP had two times higher NGAL levels than those without elevated hsCRP. NGAL was positively correlated with TNF-α, TGF-β1, and hsCRP, but not with ECP, IL-5, tIgE, and sIgE. An elevated NGAL level led to a 1.3-fold increase in the prevalence of high TGF-β1 (odds ratio: 1.31; 95% CI: 1.04–2.58; P < 0.001). In conclusion, NGAL elevation may be more closely linked to allergic inflammation and a possible fibrotic change in the airways than to the severity of eosinophil activation and atopic sensitization.

Serum neutrophil gelatinase-associated lipocalin concentrations are significantly associated with the severity of COVID-19 in pregnant patients.

Objectives:To evaluate serum neutrophil gelatinase-associated 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 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<0.001). Also, at a cutoff value of 72 ng/ml, NGAL predicted severe COVID-19 with a sensitivity rate of 57% and a specificity rate of 84%. Serum NGAL level (adjusted hazard ratio [aHR]=1.020, 95% confidence interval [CI]= [1.006-1.035], p=0.007), and D-dimer level (aHR=2.371, 95% CI= [1.085-5.181], p=0.030) were the variables that were revealed to be significantly associated with the disease severity.Conclusion:We demonstrated that NGAL was highly associated with COVID-19 severity. We consider that NGAL might be a useful biomarker to diagnose the disease severity in patients with COVID-19.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) can potentially predict vascular complications and reliably risk stratify patients with peripheral arterial disease

Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in atherosclerotic plaques and implicated in the development of cardiovascular diseases. Peripheral arterial disease (PAD) is an atherosclerotic disease that often results in major cardiovascular events. This study aimed to prospectively examine the potential of urine NGAL (uNGAL) in predicting worsening PAD status and major adverse limb events (MALE). Baseline urine NGAL (uNGAL) and urine creatinine (uCr) concentrations were measured in PAD (n = 121) and non-PAD (n = 77) patients. Levels of uNGAL were normalized for urine creatinine (uNGAL/uCr). Outcomes included worsening PAD status, which was defined as a drop in ankle brachial index (ABI) > 0.15, and major adverse limb events (MALE), which was defined as a need for surgical revascularization or amputations. PAD patients had 2.30-fold higher levels of uNGAL/uCr [median (IQR) 31.8 (17.0–62.5) μg/g] in comparison to non-PAD patients [median (IQR) 73.3 (37.5–154.7) μg/g] (P = 0.011). Multivariate cox analysis showed that uNGAL/uCr levels were independently associated with predicting worsening PAD status and MALE outcomes. Cumulative survival analysis, over follow up period, demonstrated a direct correlation between elevated uNGAL/uCr levels and PAD disease progression and MALE outcomes. These data demonstrate an association between elevated uNGAL/uCr levels and worsening PAD disease status and MALE outcomes, indicating its potential for risk-stratification of PAD patients.