The role of neutrophil gelatinase-associated lipocalin and iron homeostasis in object recognition impairment in aged sepsis-survivor rats

Older adult patients with sepsis frequently experience cognitive impairment. The roles of brain neutrophil gelatinase-associated lipocalin (NGAL) and iron in older sepsis patients remain unknown. We investigated the effects of lipopolysaccharide-induced sepsis on novel object recognition test, NGAL levels, an inflammatory mediator tumor necrosis factor-α (TNFα) levels, and iron ion levels in the hippocampus and cortex of young and aged rats. The effect of an iron chelator deferoxamine pretreatment on aged sepsis rats was also examined. Young sepsis-survivor rats did not show impaired novel object recognition, TNFα responses, or a Fe2+/Fe3+ imbalance. They showed hippocampal and cortical NGAL level elevations. Aged sepsis-survivor rats displayed a decreased object discrimination index, elevation of NGAL levels and Fe2+/Fe3+ ratio, and no TNFα responses. Pretreatment with deferoxamine prevented the reduction in the object recognition of aged sepsis-survivor rats. The elevation in hippocampal and cortical NGAL levels caused by lipopolysaccharide was not influenced by deferoxamine pretreatment. The lipopolysaccharide-induced Fe2+/Fe3+ ratio elevation was blocked by deferoxamine pretreatment. In conclusion, our findings suggest that iron homeostasis in the cortex and hippocampus contributes to the maintenance of object recognition ability in older sepsis survivors.

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

The Difference of Urinary Neutrophil Gelatinase-Associated Lipocalin Level between Liver Cirrhosis Patients with and without Hepatorenal Syndrome

Objective: To determine differences of urinary Neutrophil Gelatinase-Associated Lipocalin level in liver cirrhosis patients with or without Hepatorenal Syndrome (HRS). Methods: This study was conducted on 46 liver cirrhosis patients (20 patients without hepatorenal syndrome, 26 patients with hepatorenal syndrome). Diagnosis of HRS was based on International Ascites Club criteria. Urinary NGAL was examined using ELISA method. Data analysis was performed with p<0,05 stated as statistically significant. Result: This study showed more HRS cases was found in male than female, with an average age of 53,95 years old for hepatic cirrhosis without HRS, and 57,35 with HRS. The most common cause of this study is Hepatitis B virus, and the highest grade of severity is in Child Pugh-C. The average urinary NGAL level in liver cirrhosis with HRS is 59,39 ± 58,98 ng/ml and 130,78 ± 45,14 ng/ml in liver cirrhosis without HRS. Conclusion: There was a significant higher urinary NGAL level in liver cirrhosis with HRS (p = 0.000), with the cut-off of urinary NGAL to differentiate cirrhosis patients with and without HRS was 95,115 ng/ml. Keywords: NGAL, HRS, hepatorenal syndrome, neutrophil gelatinase-associated lipocalin.

Renal and Inflammation Markers—Renalase, Cystatin C, and NGAL Levels in Asymptomatic and Symptomatic SARS-CoV-2 Infection in a One-Month Follow-Up Study

The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters—renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine—and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies—the IG(+) group—and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies—the IG(−) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(−) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people.

Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P &lt; 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P &lt; 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p &lt; 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P &lt; 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P &lt; 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P &lt; 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation.

Plasma Neutrophil Gelatinase-associated Lipocalin and Leukocyte Differential Count in Children with Febrile Urinary Tract Infection

Purpose: We aimed to study the association of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and leukocyte differential count in children with febrile urinary tract infection (UTI).Methods: Medical records of 154 children aged 1 month to 13 years with febrile UTI who were hospitalized were retrospectively reviewed. Associations between pNGAL levels and blood leukocyte differential count at admission and after 48 hours of treatment were investigated in children with or without acute pyelonephritis (APN).Results: The APN group (n=82) showed higher pNGAL levels, neutrophil count, monocyte count, and neutrophil-to-lymphocyte ratio (NLR), compared to the non-APN group (n=72) (all P<0.05). After adjustment for age and sex, pNGAL showed positive correlations with neutrophil count and NLR in both groups (all P<0.05). Additionally, it was correlated with the monocyte-to-lymphocyte ratio (MLR) only in the APN group (P<0.05). Before and after treatment, pNGAL was positively correlated with neutrophil count, NLR, and MLR in patients with APN while it was related with neutrophil count and NLR in those without APN (all P<0.05). Areas under the receiver operating curve of pNGAL, neutrophil count, NLR, and MLR for predicting APN were 0.804, 0.760, 0.730, and 0.636, respectively (all P<0.05). Only pNGAL was independently associated with the presence of APN in a multivariable logistic regression analysis (P<0.05).Conclusion: In children with febrile UTIs, pNGAL might be associated with leukocyte differential count and the presence of APN.

Prognostic Role of Ngal In Critically Ill Patients

Background: Acute kidney injury (AKI) is a frequently encountered outcome in critically ill patients, accounting for increased mortality. Neutrophil gelatinase associated lipocalin (NGAL) has been of paramount importance as a novel biomarker of AKI. This study is an attempt to assess the use of NGAL in critically ill patients so that timely interventions can be done to reduce morbidity and mortality in such patients.Methods: A prospective observational study was conducted at SRN Hospital from August 1st 2020 to March 15th 2021, which included only critically ill patients with SOFA score>1 and requiring ICU admission. Patients of known renal diseases were excluded from the study. Blood as well as urinary samples for NGAL and other laboratory parameters were collected within 8 hours of admission. Patients who developed renal dysfunction were noted as our cases and the others were noted as controls. Results: The study was done on 125 patients, out of which 67 developed AKI while 58 did not develop AKI. Higher mortality was seen in patients with higher stage of AKI (P- 0.011). The cutoff of serum and urinary NGAL for predicting AKI were >42.3 ng/mL, >40.5 ng/mL respectively (P value <0.001). Hazard Ratio for all cause mortality of raised serum and urinary NGAL was 2.0062 (p value- 0.0001, 95% CI-1.0031 to 1.0092) and 2.0046 (p value-0.0035, 95% CI-1.0015 to 1.0078) respectively. Serum and urinary neutrophil gelatinase associated lipocalin at values >91 and >131 respectively were found to predict requirement of hemodialysis (p value<0.001).Conclusion: A single measurement of NGAL at the time of admission had good predictive ability for AKI. Higher values of NGAL were associated with staging of AKI and thus, correlated with need of hemodialysis. Furthermore, mortality was found to be associated with development of AKI and raised NGAL. Thus, NGAL maybe used to assess the prognosis of ICU patients so that patients at high risk may be managed aggressively, thus reducing mortality.