Urinary cystatin-C and urinary NGAL associated with sepsis predicts longer hospital stay in premature newborns.

Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.

[Box: see text].

Comprehensive biomarker assessment for predicting severe acute kidney injury and need of kidney replacement therapy in liver transplantation patients.

BACKGROUND: Renal dysfunction is a common complication following liver transplantation (LT). This study aimed to determine whether a comprehensive assessment of kidney function using nineteen serum and urinary biomarkers (BMs) within the first 48 h post-LT could enhance the prediction of severe acute kidney injury (AKI) and the need of kidney replacement therapy (KRT) during the first postoperative week. METHODS: Blood and urine (U) samples were collected during the pre- and postoperative periods. Nineteen BMs were evaluated to assess kidney health in the first 48 h after LT. Classification and regression tree (CART) cross-validation identified key predictors to determine the best BM combination for predicting outcomes. RESULTS: Among 100 LT patients, 36 developed severe AKI, and 34 required KRT within the first postoperative week. Preoperative assessment of U neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) predicted the need for KRT with 75% accuracy. The combined assessment of U osmolality (OSM), U kidney injury molecule 1 (KIM-1), and tissue inhibitor of metalloproteinase (TIMP-1) within 48 h post-LT predicted severe AKI with 80% accuracy. U-OSM alone, measured within 48 h post-LT, had an accuracy of 83% for predicting KRT need, outperforming any BM combination. CONCLUSIONS: Combined BM analysis can accurately predict severe AKI and KRT needs in the perioperative period of LT. U-OSM alone proved to be an effective tool for monitoring the risk of severe AKI, available in most centers. Further studies are needed to assess its impact on AKI progression postoperatively.Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title 'Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)' and identifier NCT02095431.

Acyl-CoA binding protein for the experimental treatment of anorexia.

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

Impact of Smoking and Obesity on the Selected Peptide Hormones and Metabolic Parameters in the Blood of Women with Polycystic Ovary Syndrome-Preliminary Study.

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

Serum and urinary biomarkers of vancomycin-induced acute kidney injury: A prospective, observational analysis.

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (µg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Evaluation of neutrophil gelatinase-associated lipocalin (NGAL), hypoxia-induced factor-1 alpha (HIF-1α) and apelin 13 levels as new potential biomarkers for pulmonary thromboembolism: A prospective clinical study.

AIM: The objective was to evaluate the serum levels of neutrophil gelatinase-associated lipocalin (NGAL), hypoxia-induced factor-1 alpha (HIF-1α), and apelin 13 in patients with acute pulmonary thromboembolism (PE) and to investigate their diagnostic and prognostic role in PE patients with different mortality risk groups. MATERIAL AND METHODS: This study was conducted in a tertiary referral center and included 124 subjects with 94 cases of PE and 30 cases of healthy control group. All subjects were 18 years of age or older. The diagnosis of PE was done with computed tomography angiography of the thorax. After the diagnosis of acute PE, the serum levels of neutrophil gelatinase-associated lipocalin (NGAL), hypoxia-induced factor-1 alpha (HIF-1α), and apelin 13 levels were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The median and IQR (interquartile range) age of patients and control groups were 68 (56-76) and 61.5 (56-67) years, respectively. The majority of patients with PE had risk factors (97.88 %), and only two (2.12 %) had no known risk factors. HIF-1 alpha level was found to be higher in the patient group than in the control group (p = 0.03). At the same time, the HIF-1 alpha level was found to be higher in the high mortality risk group than in the control group, low mortality risk group and intermediate-low mortality risk group (p = 0.000, 0.011, 0.002, respectively). While there was no significant difference in NGAL level between the patient group and the control group, a significant difference was observed between the mortality groups. NGAL level was found to be higher in the high mortality risk group than the control group, low mortality risk group, and medium-low mortality risk group (p = 0.001, 0.000, 0.010, respectively). Apelin 13 levels did not differ significantly in all groups. CONCLUSION: HIF-1 alpha is a promising biomarker in distinguishing between patients and control groups and in identifying those with high mortality risk in the patient group. At the same time, NGAL can be used as a successful biomarker in determining the group with high mortality risk in cases of PE.

Empagliflozin's role in early tubular protection for type 2 diabetes patients.

BACKGROUND: Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. METHODS: A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. RESULTS: Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. CONCLUSION: Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.

Detection strip of anti-NGAL antibody coupled with fluorescent microspheres-A novel tool for reliable and accurate prediction of renal injury.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) has been identified by the International Nephrology Association (INA) as a promising biomarker for the early evaluation of renal injury. This study aimed to develop and evaluate NGAL test strips as a rapid, simple, and economical method for the early diagnosis of acute kidney injury (AKI). METHODS: Recombinant prokaryotic expression vectors, purified NGAL protein, and anti-NGAL monoclonal antibodies were prepared. NGAL test strips were developed, and serum samples were collected from healthy individuals and patients with early-stage kidney injury at the Third Affiliated Hospital of Sun Yat-sen University between January 2023 and May 2024. Samples were tested using both the self-made strips and commercially available reagents. RESULTS: The NGAL test strip comprised a conjugate pad containing 0.2 µL of fluorescent microspheres conjugated with anti-NGAL monoclonal antibody (McAb7#), a test line containing 1 mg/mL of a different anti-NGAL monoclonal antibody (McAb3#), and a control line containing 0.5 mg/mL of goat anti-mouse IgG. The test utilized 60 µL of sample (30 µL serum diluted with 30 µL of sample diluent) and was completed within 15 min at 25 °C and 35 %-85 % relative humidity. The developed strip accurately detected NGAL, demonstrating good linearity within the range of 0-160 ng/mL (R2 = 0.9943). The sensitivity and specificity of the NGAL strip for AKI diagnosis were 86.1 % and 78.8 %, respectively, comparable to the performance of commercially available testing reagents. CONCLUSION: The developed test strip, utilizing anti-NGAL antibodies coupled with fluorescent microspheres, effectively detected trace amounts of NGAL protein in serum samples.

An overview of circulating and urinary biomarkers capable of predicting the transition of acute kidney injury to chronic kidney disease.

INTRODUCTION: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD. EXPERT OPINION: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.

Acute hyperbilirubinemia determines an early subclinical renal damage: Evaluation of tubular biomarkers in cholemic nephropathy.

BACKGROUND AND AIMS: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase-associated lipocalin (u-NGAL), urinary beta-2-microglobulin (u-B2M), urinary osteopontin (u-OPN), urinary trefoil factor 3 (u-TFF3) and urinary Cystatin C (u-Cys). METHODS: This is a case-control study investigating the following urinary biomarkers of tubular damage: u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys, in patients with mild acute hyperbilirubinemia. Seventy-four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. RESULTS: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u-NGAL values (OR = 3.8, 95% CI 1.07-13.5, p = .03) and u-B2M (OR = 9.4, 95% CI 2.3-38.9, p = .0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. CONCLUSIONS: This study demonstrated increased urinary biomarkers of tubular damage (u-NGAL, u-B2M, u-OPN, u-TFF3, and u-Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology).

Interleukin-6 as a Director of Immunological Events and Tissue Regenerative Capacity in Hemodialyzed Diabetes Patients.

Hemodialyzed patients have innate immunity activation and adaptive immunity senescence. Diabetes mellitus is a frequent cause for chronic kidney disease and systemic inflammation. We studied the immunological pattern (innate and acquired immunity) and the tissular regeneration capacity in two groups of hemodialyzed patients: one comprised of diabetics and the other of non-diabetics. For inflammation, the following serum markers were determined: interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumoral necrosis factor α (TNF-α), IL-6 soluble receptor (sIL-6R), NGAL (human neutrophil gelatinase-associated lipocalin), and interleukin 10 (IL-10). Serum tumoral necrosis factor ß (TNF-ß) was determined as a cellular immune response marker. Tissue regeneration capacity was studied using neurotrophin-3 (NT-3) and vascular endothelial growth factor ß (VEGF-ß) serum levels. The results showed important IL-6 and sIL-6R increases in both groups, especially in the diabetic patient group. IL-6 generates trans-signaling at the cellular level through sIL-6R, with proinflammatory and anti-regenerative effects, confirmed through a significant reduction in NT-3 and VEGF-ß. Our results suggest that the high serum level of IL-6 significantly influences IL-1ß, TNF-ß, NT-3, VEGF-ß, and IL-10 behavior. Our study is the first that we know of that investigates NT-3 in this patient category. Moreover, we investigated VEGF-ß and TNF-ß serum behavior, whereas most of the existing data cover only VEGF-α and TNF-α in hemodialyzed patients.

Synergistic impact of innate immunity hyper-activation and endothelial dysfunction on the magnitude of organ failure in the infection-sepsis continuum.

OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.

Tachycardia and Acute Kidney Injury among Critically Ill Patients with Sepsis: A Prospective Observational Study.

INTRODUCTION: Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patients' mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. METHODS: In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-ß-d-glucosaminidase (NAG) at 0 and 48 h after admission. Tachycardia was defined as a heart rate above 100 beats/min. RESULTS: Tachycardia was independently correlated with AKI prevalence during the first week after ICU admission in the septic patients, but not in the non-septic patients. A dose-dependent increase in AKI period-prevalence was observed across ascending heart rate ranges. Furthermore, we discovered a dose-dependent increase in renal biomarker-positive patients regarding plasma NGAL and urinary NAG over increasing heart rate ranges 48 h after admission. CONCLUSION: The findings revealed an independent relationship between tachycardia and AKI prevalence during the first week of ICU in septic patients. Heart rate was found to have a dose-dependent effect on AKI prevalence and renal insult monitored by biomarkers.

NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion.

Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury.

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

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

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

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

Perioperative Acute Renal Injury: Revisiting Pathophysiology.

BACKGROUND: Acute renal dysfunction and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is upregulated early (within 1 to 3 h) after murine renal injury and in pediatric acute renal dysfunction after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing acute renal dysfunction after cardiac surgery compared with patients without acute renal dysfunction. METHODS: After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. Acute renal dysfunction was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. RESULTS: Sixteen of 81 patients (20%) developed postoperative acute renal dysfunction, and the mean urinary NGAL concentrations in patients who developed acute renal dysfunction were significantly higher early after surgery (after 1 h, mean ± SD, 4,195 ± 6,520 vs. 1,068 ± 2,129 ng/ml; P < 0.01) compared with patients who did not develop acute renal dysfunction. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with acute renal dysfunction. In contrast, urinary NGAL in patients without acute renal dysfunction decreased rapidly after cardiac surgery. CONCLUSIONS: Patients developing postoperative acute renal dysfunction had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of acute renal dysfunction after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.

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

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

Lipocalin-2 as a prognostic marker in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Lipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model. METHODS: We measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice. RESULTS: Serum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration. CONCLUSIONS: Our findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients.

INTRODUCTION: Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost. METHODS: Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2). RESULTS: SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2. CONCLUSIONS: SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.