Neutrophil Gelatinase Research Articles

Early Detection of Severe Acute Kidney Injury by Urinary Neutrophil Gelatinase Associated Lipocalin in Critically Ill Children

Background: Acute Kidney Injury (AKI) is independently associated with worsened morbidity and increased mortality in critically ill children in the Pediatric Intensive Care Unit (PICU). Till date Serum Creatinine (S.Cr) is the gold standard for AKI detection. Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) is revealed as a promising novel biomarker for the early detection of kidney damage. The study is aimed to evaluate the ability of uNGAL for early detection of severe AKI in critically ill children. Materials and methods: This prospective observational study included 90 pediatric ICU (PICU) patients aged 1 month to 12 years from December 2020 to November 2021.Urine was collected for uNGAL on admission (Day 0). Blood samples were collected on Day 0 (D0), Day 3 (D3) and Day 7 (D7) for serum creatinine (S.Cr). AKI was defined and staged according to Kidney Disease Improving Global Outcomes 2012 criteria. Results: Among 90 children, 26 (28.9%) develop severe AKI on D3. The median uNGAL level was 182.9 ng/ml in children with severe AKI compared to 44.3 ng/ml in those without severe AKI. The AUC for the D0 uNGALto predict D3 severe AKI was 0.945 (CI 0.867–1.0). The best cutoff point for uNGAL was 102.70 ng/ml, with a sensitivity of 96.15% and specificity of 98.44% for D3 severe AKI. D0uNGAL had no significant correlation with D0S. Crbut had a significant positive correlation with D3 and D7 S.Cr. Conclusion: Urinary NGAL is an useful early AKI marker to detect the development of severe AKI in critically ill children of PICU. Chatt Maa Shi Hosp Med Coll J; Vol.23 (1); January 2024; Page 29-33

Activation of autophagy with PF-06409577 alleviates heatstroke-induced organ injury.

Heat waves are a significant environmental issue threatening global human health. Extreme temperatures can lead to various heat-related illnesses, with heatstroke being among the most severe. Currently, there are no effective treatments to mitigate the multi-organ damage caused by heatstroke. We found that heat stress activated autophagy. Knockdown of the autophagy-related gene 7 (ATG7) or knockout of the autophagy initiation regulatory genes UNC-51-like autophagy activating kinase 1/2 (ULK1/ULK2) increased cell death. PF-06409577, an allosteric activator of AMP-activated protein kinase β (AMPKβ), reduced heat stress-induced cell death by promoting autophagy. Inhibition of ATG7 or ULK1 weakened PF-06409577's protective effect on cells. Treatment of heatstroke mouse models with PF-06409577 suppressed high temperature-induced damage to multiple organs, including the liver, kidneys, lungs, and small intestine. PF-06409577 protected liver and kidney functions, lowered the expression of kidney injury markers neutrophil gelatinase associated lipocalin (Ngal), secreted phosphoprotein 1 (Spp1), and clusterin (Clu), and reduced levels of the inflammatory factor IL-6. Additionally, it decreased heat stress-induced macrophage infiltration and IL-6 production in the liver. The results indicate that activation of autophagy serves a protective function during heat stress, and the AMPK activator PF-06409577 exhibits potential in mitigating heatstroke-induced multi-organ damage through its ability to promote autophagy.

Lipocalin associated with neutrophil gelatinase, matrix metalloproteinases 2 and 9 in the pathogenesis of acute kidney injury in thermal skin burns

Background. Acute kidney injury is one of the most serious complications of thermal skin burns; in most cases it remains undiagnosed in the first day after injury. Therefore, it is necessary to search for new biomarkers that can indicate the onset of renal damage. Lidocaine and matrix metalloproteinases are of the greatest interest. Currently, there is insufficient information about the participation of these proteins in the development of acute kidney injury in the pathogenesis of burn disease.The aim. To evaluate the dynamics of changes in the levels of lipocalin, matrix metalloproteinases 2 and 9 in blood serum in patients with thermal skin burns.Materials and methods. The study included 74 patients with thermal skin burns of I–III degree with a skin lesion area of more than 25 %, of which at least 15 % are deep burns. Serum creatinine levels were determined using the kinetic Jaffe method. The concentration of lidocaine and matrix metalloproteinases was studied by multiplex analysis on a flow cytofluorimeter.Results. It was found that the level of lipocalin in the blood serum of patients with thermal skin burns increased 5.5 times in relation to the control group during the shock period. During the period of burn toxemia and septicotoxemia, this indicator remained at a high level and exceeded the control values. The concentration of matrix metalloproteinase 2 in blood serum during burn shock was 4.3 times higher, with burn toxemia – 3.5 times and during septicotoxemia – 2.9 times in relation to the control group. Similar dynamics was observed in the study of the level of matrix metalloproteinase 9.Conclusion. Lipocalin and matrix metalloproteinases 2 and 9 can be considered as early biomarkers of acute kidney injury in patients with thermal burns.

Corrigendum to “POS-074 SERUM NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN, EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN ASPHYXIATED TERM NEONATES AT LAGOS STATE UNIVERSITY TEACHING HOSPITAL” [Kidney International Reports Volume 7, Issue 2, Supplement, February 2022, Page S31

Corrigendum to “POS-074 SERUM NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN, EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN ASPHYXIATED TERM NEONATES AT LAGOS STATE UNIVERSITY TEACHING HOSPITAL” [Kidney International Reports Volume 7, Issue 2, Supplement, February 2022, Page S31

Does serum neutrophil gelatinase–associated lipocalin level predict acute kidney injury in patients with acute rhabdomyolysis in the emergency department? A multicentre prospective study

ObjectivesThe major complication of rhabdomyolysis is acute kidney injury (AKI), which requires prompt treatment. Currently, few biomarkers are available for the early detection of AKI. Serum neutrophil gelatinase–associated lipocalin (NGAL) has been suggested as an early biomarker for renal ischemia. However, its capacity to predict AKI in patients presenting with rhabdomyolysis in the emergency department (ED) remains unclear. The aim of this study was to evaluate the ability of NGAL to predict 48-hour AKI.DesignProspective, multicentre study.SettingFive adult EDs in France from August 2013 to December 2015.ParticipantsNGAL levels were measured on ED admission in patients with rhabdomyolysis. A total of 197 patients were enrolled, and 189 (96%) were analysed, of whom 89 (47%) were women. Patients were included if they presented to the ED with rhabdomyolysis and a creatine phosphokinase (CPK) level above 1000 IU/L. Exclusion criteria were pregnancy, presentation with acute coronary syndrome, the need for iodinated contrast, chronic dialysis or recent use of nephrotoxic drugs (within 72 hours prior to the ED visit). Patients who withdrew consent or had AKI due to other causes were also excluded.Primary and secondary outcome measuresThe primary outcome was AKI at 48 hours, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included in-hospital mortality, length of hospital stay, admission to intensive care and the need for renal replacement therapy.ResultsOverall, 54 (29%) patients developed AKI by day 2. The area under the ROC curve (AUC-ROC) for NGAL in predicting AKI on day 2 was 0.60 (95% CI 0.51 to 0.70), with an optimal cut-off of 129 ng/mL. The sensitivity was 0.65, and specificity was 0.50. After adjustment for CPK levels, age, sex and oxygen saturation, the AUC-ROC for predicting AKI on day 2 increased slightly to 0.64 (95% CI 0.54 to 0.74).ConclusionNGAL has limited ability to predict day 2 AKI in patients presenting with acute rhabdomyolysis in the ED.Trail registration numberNCT01544231.Comité de Protection des Personnes Sud Méditerranée III n°2011-A01059-32.

Assessment of Neutrophil Gelatinase Associated Lipocalin in Children with Acute Gastroenteritis and Dehydration to Identify Early Signs of Acute Kidney Injury

Background: Gastroenteritis often correlates with acute kidney injury (AKI) in children who are hospitalized. The primary diagnostic test for acute kidney injury (AKI) in modern times is serum creatinine (SCr), which increases in the presence of AKI and is eliminated by glomerular filtration. SCr is an unsuitable biomarker for renal sickness because it lacks specificity and a slow response to disease severity or treatment changes. NGAL, or neutrophil gelatinase-associated lipocalin, is a molecular weight of 25 kDa protein and forms a covalent bond with neutrophil gelatinase. Elevations in NGAL levels due to kidney injury have important predictive value and may forecast the onset of acute kidney injury (AKI) 24-72 hours before an increase in diagnostic serum creatinine (SCr) values. Aim and objectives: This study aims to determine whether plasma NGAL concentrations in mild, moderate, or severe dehydrated acute gastroenteritis patients may indicate acute kidney damage (AKI). The research will investigate whether acute renal injury and plasma NGAL concentrations are connected. Patients and methods: The cross-sectional design was employed in this study and included 80 patients who attended the pediatric gastrointestinal clinic at Babylon Children's Hospital. Between November 2022 and June 2023, all patients had gastroenteritis symptoms accompanied by different dehydration levels. Results: Patients with severe dehydration had considerable higher level of NGAL than those with mild to moderate dehydration (p<0.001). There was a notable inverse relationship (p = 0.046) between the NGAL level and potassium but a considerable direct link (p<0.001) between the NGAL level and creatinine. However, no significant correlation was seen between the NGAL level and urea (p = 0.404 and 0.062, respectively). The confidence range for the area under the curve (AUC) is 0.940 to 0.981, with a confidence level of 95%. The p-value is less than 0.001. The sensitivity is 88%. An accuracy of 88.4% has been attained. The NGAL cut-off point is 3.9832. Conclusion: An analysis of plasma neutrophil gelatinase-associated lipocalin (NGAL) in individuals with gastroenteritis and varied degrees of dehydration indicated a clear and direct link between the two parameters. Specifically, when dehydration worsened, the average NGAL value increased

Plasma procalcitonin and urine interleukin-8, neutrophil gelatinase–associated lipocalin, and calprotectin in the diagnostic process of a urinary tract infection at the emergency department

ObjectivesThis study aimed to assess the usefulness of plasma procalcitonin and urine IL-8 (interleukin-8), NGAL (neutrophil gelatinase–associated lipocalin), and calprotectin for diagnosis of urinary tract infections (UTIs) at the emergency department (ED). MethodsIn adults presenting at the ED with UTI suspicion, biomarker performance was compared with that of routine diagnostics (urine dipstick, automated urinalysis). Patients with a urine catheter, leukopenia, or neither (standard) were analyzed separately. ResultsA UTI was clinically diagnosed in 91 of 196 episodes (46.4%) (standard: 29/67 [43.2%]; catheter: 46/73 [63.0%]; leukopenia: 17/60 [28.3%]; four patients had both). Procalcitonin did not discriminate between UTI and no UTI. Urinary biomarker levels were elevated in UTI episodes (median, µg/mmol creatinine: NGAL, 7.8 vs 46.3; IL-8, 6.1 vs 76.6; calprotectin, 23.9 vs 265.4); the three subgroups also had higher levels. Biomarker cut-off values (90% sensitivity) showed low specificity (range 20.8-64.9%) and moderate accuracy (58.6-75.4%). The biomarkers performed similarly to routine diagnostics, except for patients with leukopenia, who exhibited nonsignificantly higher area under the curve values. All urinary biomarkers correlated positively with urine leukocyte count. ConclusionPlasma procalcitonin could not accurately diagnose UTI. Urine IL-8, NGAL, and calprotectin showed no additional value relative to routine diagnostics, except a minor improvement in patients with leukopenia. These urine biomarkers seem to predominantly reflect leukocyturia.

A silver auto-catalyzed plasmonic enzyme-linked immunosorbent assay for colorimetric and fluorescent detection of neutrophil gelatinase associated lipocalin (NGAL)

The conventional ELISA lacked sufficient sensitivity and accuracy for analyzing neutrophil gelatinase associated lipocalin (NGAL), a potential biomarker of ulcerative colitis. Here, we developed a dual-readout plasmonic ELISA with cascade amplification of alkaline phosphatase hydrolysis and O-phenylenediamine oxidation. In this novel plasmonic ELISA, alkaline phosphatase-conjugated antibodies capture NGAL from samples, alkaline phosphatase hydrolyzes 2-phospho-L-ascorbic acid into ascorbic acid, and then ascorbic acid blocks silver-catalyzed O-phenylenediamine oxidation by turning silver ions into silver microwires. Therefore, NGAL concentration is proportional to the decrease in chromogenic and fluorescent response. This novel plasmonic ELISA exhibited a linear range of 0.5–80 ng/mL, and the LOD was as low as 0.5 ng/mL. The sensitivity was superior to that of conventional ELISA and previous studies. The plasmonic ELISA exhibited favorable selectivity because of the specific antibody-antigen interaction and the robust cascade amplification. Besides, the dual-readout feature endowed the plasmonic ELISA with advantages in terms of convenience and compatibility. In summary, our study provided a novel and sensitive plasmonic ELISA for the diagnosis of ulcerative colitis.

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 30days (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.

Value of Urine Neutrophil Gelatinase Associated Lipocalin for Prediction of Ureteropelvic Junction Obstruction in Children

Background: Congenital obstructive nephropathy is a significant cause of chronic kidney damage in childhood. Therefore, early diagnosis and management of urinary tract obstruction are necessary to prevent or reduce further renal damage. Various biomarkers have been investigated for the early identification of urinary tract obstruction. Objectives: The aim of this study was to evaluate the excretion of urine neutrophil gelatinase-associated lipocalin (Urine neutrophil gelatinase-associated lipocalin (uNGAL) & uNGAL/Cr) as a useful, sensitive, and non-invasive diagnostic biomarker in children with ureteropelvic junction obstruction (UPJO). Methods: The study cohort consisted of 47 children with obstructive UPJO and 47 healthy children with normal renal ultrasounds. Ultrasonography and 99mTc DTPA radionuclide scans were used for diagnosing UPJO. All affected children had normal renal function based on GFR measurements. Urine neutrophil gelatinase-associated lipocalin was measured using Immunoenzymatic ELISA commercial kits. Results: Urine neutrophil gelatinase-associated lipocalin & uNGAL/Cr levels were significantly higher in children with obstructive UPJO compared to the healthy control group. Additionally, both biomarkers demonstrated acceptable sensitivity and specificity for predicting for predicting UPJO. Conclusions: Based on these results, measuring uNGAL & uNGAL/Cr is suggested for evaluating children with obstructive UPJO.

Insomnia and sleep duration for kidney function: Mendelian randomization study

Objectives Extensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR). Methods Independent genetic variants strongly associated with insomnia (N = 462,341) and sleep duration (N = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate. Results MR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the p-values in multivariable MR analysis became nonsignificant. No pleiotropy was detected. Conclusions This study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.

Prediction of cardiac surgery associated acute kidney injury using response to loop diuretic and urine neutrophil gelatinase associated lipocalin

BackgroundCardiac surgery associated acute kidney injury (CS-AKI) is common. Urine response to loop diuretic and urine neutrophil gelatinase associated lipocalin (uNGAL) are separately associated with CS-AKI. We aimed to determine whether urine response to loop diuretic and uNGAL together were associated with postoperative day 2–4 CS-AKI.MethodsTwo-center prospective observational study (ages 0–18 years). uNGAL (8–12 h after admission) (ng/mL) and urine response to loop diuretic (6 h for bolus furosemide and 12 h for infusion bumetanide) (mL/kg/hr) were measured. All diuretic doses were converted to furosemide equivalents. The primary outcome was day 2–4 CS-AKI. Patients were sub-phenotyped using a priori cutoffs (uNGAL + ≥ 100 ng/mL and UOP + < 1.5 mL/kg/hr) and optimal cutoffs (uNGAL + ≥ 127 ng/mL and UOP + ≤ 0.79 mL/kg/hr): 1) uNGAL–/UOP–, 2) uNGAL–/UOP + , 3) uNGAL + /UOP–, and 4) uNGAL + /UOP + . Multivariable regression was used to assess the association of uNGAL, UOP and each sub-phenotype with outcomes.Results476 patients were included. CS-AKI occurred in 52 (10.9%). uNGAL was associated with 2.59-fold greater odds (95%CI: 1.52–4.41) of CS-AKI. UOP was not associated with CS-AKI. Compared with uNGAL + alone, uNGAL + /UOP + improved prediction of CS-AKI using a priori and optimal cutoffs respectively (AUC 0.70 vs. 0.75). Both uNGAL + /UOP + (IQR OR:4.63, 95%CI: 1.74–12.32) and uNGAL + /UOP– (IQR OR:5.94, 95%CI: 2.09–16.84) were associated with CS-AKI when compared with uNGAL–/UOP–.ConclusionsuNGAL is associated with CS-AKI. The sub-phenotype association was largely driven by uNGAL. Future studies standardizing diuretic dose and timing may be needed to refine the combined performance for clinical decision making.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

A novel pharmacological strategy using nanoparticles with glutathione and virgin coconut oil to treat gentamicin-induced acute renal failure in rats

In acute renal failure (ARF), the glomerular filtration rate is reduced, and nitrogenous waste products accumulate persistently, which can last anywhere from a few hours to several days. There is hope for a reversal of the rapid loss of renal function caused by this condition. This study, with gentamicin-induced acute ARF as a prospective setting, sets out to examine the reno-protective benefits of virgin coconut oil (VCO) and GSH. Furthermore, the study evaluated the effect of medication nanoparticle compositions on several kidney function markers. The induction of ARF is achieved with the intraperitoneal injection of gentamicin. To assess renal function, rats underwent 24 h of dehydration and hunger before their deaths. The study examined various aspects, including kidney function tests, markers of oxidative stress, histology of kidney tissue, inflammatory cytokines, immunohistochemistry expression of nuclear factor-kappa B (NF-κB), and specific biomarkers for kidney tissue damage, such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase–associated lipocalin (NGAL). The results of our study indicated that the combination of VCO and GSH, using both regular and nanoparticle formulations, had a better protective impact on the kidneys compared to using either drug alone. The recovery of renal tissue and serum markers, which are symptomatic of organ damage, indicates improvement. This was also demonstrated by the reduction in tubular expression of TNF-α, IL-1β, KIM-1, and NGAL. The immunohistochemical studies showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of NF-κB. The study shows that VCO and GSH, when administered individually or combined, significantly improve ARF in a gentamicin-induced rat model, highlighting potential therapeutic implications. Notably, the combined nanoparticulate formulations exhibit substantial effectiveness.

Human Adipose Tissue-Derived Stromal Cells Ameliorate Adriamycin-Induced Nephropathy by Promoting Angiogenesis

ABSTRACT This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks’ treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

#976 Empagliflozin limits AKI incidence and severity following cardiac surgery: an open-label phase IV randomized pilot study

Abstract Background and Aims Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent complication of cardiac surgery assisted by cardiopulmonary bypass (CPB). Currently, no effective preventative strategies exist to reduce the incidence of acute kidney injury (AKI). Sodium-glucose transport protein 2 (SGLT2) inhibitors are effective in reducing the incidence of AKI in studies conducted in patients with chronic kidney disease. Therefore, we hypothesized that perioperative SGLT2 inhibition could reduce the incidence of CSA-AKI. Method In this open-label phase IV, randomized, parallel-group, balanced (1:1), pilot study, adult patients undergoing elective cardiac surgery with CPB were randomized to receive 10 mg empagliflozin per os once daily three days before surgery until two days after surgery, or standard care. The primary outcome was AKI incidence according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Other outcomes included hypoxia-inducible factor 1 alpha (HIF1A) and urinary Kidney Injury Molecule (KIM-1), urinary neutrophil gelatinase associated lipocalin (NGAL) and metabolic parameters such as plasma ketone and glucose concentrations. Results Between March 2022 and April 2023, 60 patients were randomized to empagliflozin (n = 29) or control (n = 31). All patients who underwent cardiac surgery with CPB were included in the intention-to-treat analysis (n = 25; empagliflozin group, n = 30; control group). SGLT2 inhibition significantly reduced the incidence of all stages of AKI (20% vs 66.7%; absolute difference 46%, 95% CI .13 to .63, P &amp;lt; .001). This decline in AKI incidence was reflected in the kidney biomarkers. SGLT2 inhibition also significantly reduced the number of patients with postoperative hyperglycemia (28% vs 60%; absolute difference 32%, 95% CI −56.8 to −7.2, P = .029). We observed no differences in the incidence of neither ketoacidosis nor hypoglycemic events. Conclusion Perioperative SGLT2 inhibition, compared with standard of care, demonstrated a significant reduction in AKI incidence rates. These findings merit validation in a larger placebo-controlled trial which is currently ongoing. Supplementary figures:

#668 Combined biomarker testing for the assessment of acute kidney injury among myocardial infarction patients

Abstract Background and aims The utility of different biomarkers for the prediction of acute kidney injury following ST-elevation myocardial infarction (STEMI) has been evaluated in several studies however, very few data exist on the prognostic value of combining biomarkers. Among numerous biomarkers examined, C-reactive protein (CRP) and Neutrophil gelatinase associated Lipocalin (NGAL) stand high in their utility to assess AKI risk. The aim of this study was to assess the prognostic value of combined CRP and NGAL measurement for the assessment of the risk of AKI in reperfused STEMI patients Methods Blood samples for plasma NGAL and CRP were drawn 24 hours after admission. High NGAL and CRP were defined as values within the 4th quartile (&amp;gt;75percentile). Patients were stratified into 4 study groups: Low NGAL/Low CRP, LOW NGAL/high CRO, High NGAL /low CRP and high NGAL/high CRP. Patients were assessed for the occurrence of in-AKI based on the KDIGO criteria. Results A total of 311 patients were included (mean age 66 ± 14 years, 81% males). According to the 4 study groups, there was a stepwise increase in the proportion of AKI (9% vs. 21% vs. 40% vs. 68%; p 0.001; Fig. 1). In a multivariate regression model, compared to patients having low NGAL/low CRP we observed a graded, independent increase in the risk for AKI for low NGAL/high CRP, high NGAL/low CRP and high NGAL/high CRP(OR 2.89, p = 0.02 vs. OR 3.29, p &amp;lt; 0.001 vs. OR 17.6, p &amp;lt; 0.001 respectively, Table 1). Peak concentrations showed significant areas under the curves (AUCs) for the prediction of AKI for both CRP AUC (0.692, 95% CI 0.62-0.76) and NGAL (AUC 0.778, 95% CI 0.72-0.84). The combination of NGAL and CRP yielded a significant increase in AUC to 0.822 (95% CI 0.77 to 0.88) (combined biomarkers vs CRP: p &amp;lt; 0.001 and combined vs. NGAL: p = 0.02; Fig. 2). Conclusions In patients with reperfused STEMI, the combined assessment of NGAL and CRP provided incremental prognostic information for the prediction AKI when compared with single-biomarker measurement.

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

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

Role of Osteopontin and NGAL in Differential Diagnosis of Acute Exacerbations of COPD and Pneumonia

Objective: Chronic Obstructive Pulmonary Diesase (COPD) is an inflammatory lung disease that progresses with attacks. Pneumonia is an infectious lung disease that progresses with lung infiltrations. Osteopontin (OP) is a cytokine which participates in inflammation. Neutrophil Gelatinase Associated Lipocalin (NGAL) is an antimicrobial peptide with neutrophil activation and antibacterial properties. In this study, serum OP and NGAL levels were assayed in COPD exacerbation, stabile COPD and pneumonia. The aim of our study is to assess the importance of NGAL and OP levels as biomarkers in the differential diagnosis of COPD and pneumonia. Material and Methods: One hundred twenty consecutive patients who were admitted to our department between May 2011 and August 2013 were included in the study. Serum OP and NGAL levels were measured with ELISA method within 24 hours following the determination of diagnosis. COPD acute exacerbation (AE-COPD) group was comprised of 95 patients (87 male and mean age 69.0±10.6), and the pneumonia group was comprised of 25 patients (16 male and mean age 57.5±22.9). Serum OP and NGAL levels of the patients in the AE-COPD group were re-measured within 30-45 days following acute exacerbation in stabile period. Results: Serum OP levels were higher in the pneumonia group compared to the AE-COPD group (93.47 ng/ml vs 53.10 ng/ml; p&lt;0.001). Multivariate regression analyses indicated that OP levels to be &gt;84 ng/ml is an independent predictor that increases risk for pneumonia more than 8-fold (95% CI, 2.43-26.59). Sensitivity and specificity of OP in the differentiation of pneumonias from AE-COPD were determined to 80% and 92%, respectively. Serum NGAL levels also increased as COPD severity increased and was found to be statistically significant (p: 0.032). Conclusion: It has been indicated that serum osteopontin level can be an independent predictor in differentiating COPD exacerbation from pneumonia. Additionally, as COPD severity (stage) increases, serum NGAL levels also increase, which may be helpful in assessing the severity of COPD.

Effect of verbascoside against acute kidney injury induced by rhabdomyolysis in rats.

Rhabdomyolysis is a pathological condition caused by muscle tissue degradation. In this condition, intracellular contents enter the bloodstream, and acute kidney injury (AKI) develops. Verbascoside (VB) is one of the most common phenylethanoid glycosides and has antioxidant and anti-inflammatory effects. This study investigated the effects of VB on AKI induced by rhabdomyolysis in rats. Male Wistar rats were divided into six groups (n = 6): (1) control group (normal saline), (2) 50% glycerol (10 ml/kg, IM, single injection, only on the first day), (3)-(5) 50% glycerol (same as group 2) + VB (30, 60, and 100 mg/kg, IP, 4 days), and (6) VB (100 mg/kg). Serum and kidney tissue samples were collected on day 5. Subsequently, serum creatinine (Cr), blood urea nitrogen (BUN), renal glutathione (GSH), malondialdehyde (MDA), lipocalin associated with neutrophil gelatinase (NGAL), tumor necrosis factor-alpha (TNF-α), and pathological changes were investigated. The injection of glycerol elevated levels of kidney damage markers, including Cr and BUN in serum, MDA, TNF-α, and NGAL, along with a reduction in GSH levels in the kidney tissue. The administration of VB (100 mg/kg) significantly lowered the levels of these markers, indicating the therapeutic effect of VB against AKI caused by rhabdomyolysis. Histopathological examinations revealed enhanced myoglobin cast formation and tubular necrosis in the glycerol group, which was reduced in rats that received VB, although this reduction did not reach statistical significance. VB can reduce rhabdomyolysis-induced AKI through its anti-inflammatory and antioxidant effects and decrease kidney damage severity.

STAT1 regulates neutrophil gelatinase B-associated lipocalin induction in influenza-induced myocarditis

Influenza is a significant public health and economic threat around the world. Epidemiological studies have demonstrated a close association between influenza pandemics and cardiovascular mortality. Moreover, it has been shown that there is a decrease in cardiovascular mortality in high-risk patients following vaccination with the influenza vaccine. Here, we have investigated the role of anti-viral STAT1 signaling in influenza-induced myocarditis. Wild-type mice (C57BL/6) were infected with either influenza A/PR/8/34 or control, and cellular response and gene expression analysis from the heart samples were assessed 7 days later. The expression of interferon response genes STAT1, STAT2, Mx1, OASL2, ISG15, chemokines CCL2, CCL3, CXCL9 and CXCL10, and the frequency of neutrophils (CD45+CD11b+Ly6G+) and CD4+ T cells (CD45+CD4+) were all significantly increased in influenza-infected mice when compared to vehicle controls. These data suggest that influenza infection induces interferons, inflammatory chemokines, and cellular recruitment during influenza infection. We further investigated the role of STAT1 in influenza-induced myocarditis. The frequency of neutrophils and the levels of lipocalin 2 were significantly increased in STAT1−/− mice when compared to WT controls. Finally, we investigated the role of Lcn2 in viral-induced myocarditis. We found that in the absence of Lcn2, there was preserved cardiac function in Lcn2−/− mice when compared to WT controls. These data suggest that the absence of Lcn2 is cardioprotective during viral-induced myocarditis.