Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

Nephroprotective effects of diminazene on doxorubicin-induced acute kidney injury in rats

This study aimed to investigate the potential protective effects of diminazene, an activator of angiotensin II converting enzyme (ACE2), on kidney function and structure in rats with acute kidney injury (AKI) induced by the anticancer drug doxorubicin (DOX). The impact of diminazene was compared to that of two other drugs: the ACE inhibitor lisinopril and the angiotensin II type 1 (AT1) receptor blocker valsartan. Rats were subjected to a single intraperitoneal injection of DOX (13.5 mg/kg) on the 5th day, either alone or in combination with diminazene (15 mg/kg/day), lisinopril (10 mg/kg/day), or valsartan (30 mg/kg/day) for 8 consecutive days. Various markers related to kidney function, oxidative stress, and inflammation were measured in plasma and urine. Additionally, kidney tissues were assessed histopathologically. DOX-induced nephrotoxicity was confirmed by elevated levels of plasma urea, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL). DOX also led to increased urinary N-acetyl-β-D-glucosaminidase (NAG) activity and decreased creatinine clearance, albumin levels, and osmolality. Moreover, DOX caused a reduction in renal oxidative stress markers, including superoxide dismutase (SOD), glutathione reductase (GR), and catalase activities, while increasing malondialdehyde (MDA) levels. It also raised plasma inflammatory markers, tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). Concurrently administering diminazene significantly mitigated these DOX-induced changes, including histopathological alterations like renal tubule necrosis, tubular casts, shrunken glomeruli, and increased renal fibrosis. Similar protective effects were observed with lisinopril and valsartan. These protective effects, at least in part, appear to result from the anti-inflammatory and antioxidant properties of these drugs. In summary, this study suggests that the administration of diminazene, lisinopril, or valsartan had comparable effects in ameliorating the biochemical and histopathological aspects of DOX-induced acute kidney injury in rats.

Novel biochemical markers for the prediction of renal injury in beta-thalassemia major pediatric patients

Beta-thalassemia major is a severe inherited disorder characterized by inadequate production of hemoglobin beta chains, ineffective erythropoiesis, chronic hemolysis and necessitates lifelong transfusions, which lead to iron overload. The disease manifests itself in early childhood and persists throughout an individual’s life with a high risk of developing renal impairment, which cannot be reliably determined using routine markers. The objective of this research was to apply biomarkers to the evaluation of renal injury in pediatric­ patients within the age range of 1–14 years diagnosed with beta-thalassemia major. In the case-control study, the blood samples obtained in the Genetic Hematology Center in Thi-Qar Iraq Province were used: 60 samples from healthy individuals and 60 samples from the patients with beta-thalassemia, subdivided into 1-7 and 8-14 years old groups. The levels of hemoglobin, ferritin, creatinine and potassium were estimated with standard tests, enzyme-linked immunoassay was used to determine the level of neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) as novel markers of tubular and glomerular dysfunctions. The study revealed a statistically significant decrease in hemoglobin, serum potassium levels and an increase in ferritin, NGAL and β2M levels in the patients from both groups compared to controls and elevation of creatinine level in the 8–14-year-old group. It was concluded that NGAL and β2M levels may be considered indicators for the early diagnosis of renal injury in pediatric patients with beta-thalassemia, as these biomarkers exhibit elevated levels before an increase in creatinine is observed. Keywords: beta-2-microglobulin, beta-thalassemia major, creatinine, ferritin, neutrophil gelatinase-associated lipocalin, renal injury

Curcumin supplementation prevents cisplatin-induced nephrotoxicity: a randomized, double-blinded, and placebo-controlled trial.

Cisplatin-induced nephrotoxicity (CIN) remains the most prevailing unfavorable influence and may affect its clinical usage. This study sought to explore the possible impacts of curcumin on preventing CIN in human subjects. The investigation was a placebo-controlled, double-blinded, randomized clinical trial conducted on 82 patients receiving nano-curcumin (80 mg twice daily for five days) or an identical placebo with standard nephroprotective modalities against CIN. Data was gathered on patients' demographics, blood, urinary nitrogen, creatinine (Cr) levels, urinary electrolytes, and urine neutrophil gelatinase-associated lipocalin (NGAL) levels in treatment and placebo groups, 24 h and five days after initiating the administration of cisplatin. Both investigation groups were alike considering the demographic characteristics and clinical baseline data. Curcumin administration led to a significant improvement in blood-urine nitrogen (BUN). BUN, Cr, glomerular filtration rate (GFR), and the ratio of NGAL-to-Cr considerably altered during the follow-up periods. However, the further alterations in other indices, including urinary sodium, potassium, magnesium, NGAL values, and potassium-to-Cr ratio were not statistically noteworthy. The significant differences in the NGAL-to-Cr ratio between the two groups may indicate the potential protective impact of curcumin supplementation against tubular toxicity. Curcumin management was safe and well-accepted; only insignificant gastrointestinal side effects were reported. Curcumin supplementation may have the potential to alleviate CIN and urinary electrolyte wasting in cancer patients. Future research investigating the effects of a longer duration of follow-up, a larger participant pool, and a higher dosage of curcumin are recommended.

Study of hispidulin in the treatment of uric acid nephropathy based on NF-κB signaling pathway.

Uric acid nephropathy (UAN) is caused by purine metabolism disorders. UAN rat models were established in SD rats. The modeling rats received different doses of hispidulin (10, 20, 50 mg/mL). Febuxostat was applied as the positive drug. Serum creatinine, uric acid (UA), and cystatin-C (cys-C), neutrophil gelatinase-associated lipocalin (NGAL), IL-1β, IL-8, TNF-α, and IL-6 in rats were detected. HE staining was done to assess kidney injury. UAN rats possessed prominent levels of serum creatinine, UA, cys-C, and NGAL, which all reduced after hispidulin treatment in a dose-dependent manner. HE staining determined the improvement of kidney injury after treatment, which was comparable to the efficacy of febuxostat. Hispidulin inhibited the release of IL-1β, IL-8, TNF-α, and IL-6 in UAN rats. Hispidulin enhanced autophagy in UAN rats, presenting as ascending LC3II/I ratio and downregulated P62. The increasing trend of inflammasome-related proteins of NLRP3 and Caspase-1 was changeovered by hispidulin. The activation of NF-kB signaling was intercepted by hispidulin in UAN rats. Hispidulin can effectively improve renal function injury caused by UAN in rats. The mechanism may be related to the inhibition of inflammatory response induced by autophagy and activation of NF-κB pathway.

NO Addition during Gas Oxygenation Reduces Liver and Kidney Injury during Prolonged Cardiopulmonary Bypass.

Objective. To evaluate the effect of NO added to the sweep gas of the oxygenator during cardiopulmonary bypass (CPB) on the liver and kidneys in pigs. Methods. An experiment was carried out on 10 pigs undergoing cardiac surgery using CPB. NO was added to the sweep gas of the oxygenator at a concentration of 100 ppm for the animals in the experimental group (CPB-NO, n = 5). Animals in the control group (CPB-contr, n = 5) did not receive NO in the sweep gas of the oxygenator. The CPB lasted 4 h, followed by postoperative monitoring for 12 h. To assess the injury to the liver and kidneys, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were determined initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. The glomerular filtration rate (GFR) was evaluated initially, at weaning from the CPB, and 6 and 12 h after weaning from the CPB. A pathomorphological study of the liver and kidneys was performed using semiquantitative morphometry. Results. The long four-hour period of CPB deliberately used in our experiment caused liver and kidney injury. In the CPB-contr group, an increase in the ALT concentration was found: 43 (34; 44) U/L at baseline to 82 (53; 99) U/L 12 h after CPB, p < 0.05. The AST concentration in the CPB-contr group increased from 25 (17; 26) U/L at baseline to 269 (164; 376) U/L 12 h after CPB, p < 0.05. We found no significant increase in the ALT and AST concentrations in the CPB-NO group. There were no significant differences in ALT and AST concentrations between the CPB-NO and CPB-contr groups at all the study time-points. In the CPB-contr group, an increase in the creatinine level was found from 131 (129; 133) µmol/L at baseline to 273 (241; 306) µmol/L 12 h after CPB, p < 0.05. We found no significant increase in creatinine level in the CPB-NO group. Creatinine levels in the CPB-NO group were significantly lower than in the CPB-contr group 12 h after weaning from CPB: 183 (168; 196) vs. 273 (241; 306) µmol/L; p = 0.008. The GFR in the CPB-NO group was significantly higher than in the CPB-contr group 6 h after weaning from CPB: 78.9 (77.8; 82.3) vs. 67.9 (62.3; 69.2) mL/min; p = 0.016. GFR was significantly higher in the CPB-NO group than in the CPB-contr group 12 h after weaning from CPB: 67.7 (65.5; 68.0) vs. 50.3 (48.7; 54.9) mL/min; p = 0.032. We found no significant differences between the study groups in the level of NGAL. We found several differences between the groups in the pathomorphological study. Conclusions. NO added to the sweep gas of the oxygenator reduces creatinine levels and increases GFR during prolonged CPB injury. Further research is required.

Plasma NGAL levels in stable kidney transplant recipients and the risk of allograft loss.

The objective of this study was to investigate the utility of neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin (CPT) to predict long-term graft survival in stable kidney transplant recipients (KTR). A total of 709 stable outpatient KTR were enrolled >2 months post-transplant. The utility of plasma and urinary NGAL (pNGAL, uNGAL) and plasma and urinary CPT at enrollment to predict death-censored graft loss was evaluated during a 58-month follow-up. Among biomarkers, pNGAL showed the best predictive ability for graft loss and was the only biomarker with an area under the curve (AUC)>0.7 for graft loss within 5 years. Patients with graft loss within 5 years (n=49) had a median pNGAL of 304 [interquartile range (IQR) 235-358] versus 182 (IQR 128-246) ng/mL with surviving grafts (P<.001). Time-dependent receiver operating characteristic analyses at 58 months indicated an AUC for pNGAL of 0.795, serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) had an AUC of 0.866. pNGAL added to a model based on conventional risk factors for graft loss with death as competing risk (age, transplant age, presence of donor-specific antibodies, presence of proteinuria, history of delayed graft function) had a strong independent association with graft loss {subdistribution hazard ratio (sHR) for binary log-transformed pNGAL [log2(pNGAL)] 3.4, 95% confidence interval (CI) 2.24-5.15, P<.0001}. This association was substantially attenuated when eGFR was added to the model [sHR for log2(pNGAL) 1.63, 95% CI 0.92-2.88, P=.095]. Category-free net reclassification improvement of a risk model including log2(pNGAL) in addition to conventional risk factors and eGFR was 54.3% (95% CI 9.2%-99.3%) but C-statistic did not improve significantly. pNGAL was an independent predictor of renal allograft loss in stable KTR from one transplant center but did not show consistent added value when compared with baseline predictors including the conventional marker eGFR. Future studies in larger cohorts are warranted.

Alleviation effects of epigallocatechin-3-gallate against acute kidney injury following severe burns

BackgroundBurn patients often face a high risk of acute kidney injury (AKI) after severe burn injuries, meanwhile epigallocatechin-3-gallate (EGCG) has been proven to be effective in alleviating organ injury.MethodsThis study used the classical burn model in rats. Thirty model rats were randomly divided into a Burn group, a Burn + placebo group, a Burn + EGCG (50 mg/kg) group, and ten non-model rats as Sham group. The urinary excretion of the rats was subsequently monitored for a period of 48 h. After 48 h of different treatments, rat serum and kidneys were taken for the further verification. The efficacy of EGCG was assessed in pathological sections, biochemical indexes, and at the molecular level.ResultsPathological sections were compared between the Burn group and Burn + placebo group. The rats in the Burn + EGCG group had less kidney damage. Moreover, the EGCG group maintained significantly elevated urine volumes, biochemical indexes manifested that EGCG could reduce serum creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL) level and inhibit the oxidation-related enzyme malondialdehyde (MDA) level, meanwhile the superoxide dismutase (SOD) level was increased. The molecular level showed that EGCG significantly reduced the mRNA expression levels of the inflammation-related molecules interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).ConclusionThe research indicated that EGCG had an alleviating effect on kidney injury in severely burned rats, and its alleviating effects were related to improving kidney functions, alleviating oxidative stress, and inhibiting the expression of inflammatory factors.

Values of serum neutrophil gelatinase-associated lipocalin and cystatin C after percutaneous coronary intervention for early diagnosis of contrast-induced nephropathy.

Serum creatinine (SCr) is not a sensitive and reliable index for the early diagnosis of acute kidney injury caused by contrast-induced nephropathy (CIN). The aim of this study was to explore the values of serum neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys-C) after percutaneous coronary intervention (PCI) for the early diagnosis of CIN. Three hundred patients receiving PCI from January 2018 to December 2020 were assigned to a CIN group (n=25) and a non-CIN group (n=275), respectively. SCr, Cys-C and NGAL levels were measured, and their sensitivities for early CIN diagnosis were evaluated by the area under the receiver operating characteristic curve (AUC) values. The NGAL and Cys-C levels of the CIN group began to rise 6 and 12 h after operation, respectively (P<0.05). The CIN group had higher NGAL and Cys-C levels than those of the non-CIN group 12, 24 and 48 h after operation (P<0.05). The AUC values of NGAL, Cys-C and SCr 24 h after operation were 0.885, 0.874 and 0.856, respectively. The serum NGAL and Cys-C levels of patients after PCI reflect the early changes of renal function, which are valuable for early CIN diagnosis.

A Cross-Sectional Study of Urinary Neutrophil Gelatinase-Associated Lipocalin and its Association with Steroid Responsiveness in Iraqi Children with Idiopathic Nephrotic Syndrome

Background: Steroid-resistant nephrotic syndrome (SRNS)is associated with serious complications and financial burdens. Studies reported increased urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in children with idiopathic nephrotic syndrome (INS). Objectives: This study aimed to evaluate the uNGAL potential to distinguish SRNS from steroid-sensitive nephrotic syndrome (SSNS) in Iraqi children. Patients and Methods: Children with SRNS (n=31) and SSNS (n=32) were recruited from Babylon Hospital for Maternity and Pediatrics from March to June 2022. Patients' data included demographics, clinical characteristics, and urinary lab tests. The uNGAL concentrations were measured via a commercially available ELISA kit. Results: A significantly higher uNGAL median (p-value&lt;0.001) was noted in the SRNS group (median [IQR] = 131.512 [30.28] ng/mL) than in the SSNS group (88.45 [41.6] ng/mL). The correlation between uNGAL levels and estimated glomerular filtration rate (eGFR) was negative (Spearman's rho coefficient = − 0.599, p&lt;0.001). The discriminatory power ofuNGAL to discern SRNS from SSNS was significantly high (AUC=0.899, p&lt;0.0001) with a sensitivity of 87.1% and specificity of 87.5% at an optimal cut-off value of 111.091 ng/mL. Conclusion: uNGAL is associated with a reliable discriminatory strength to distinguish, noninvasively, children with SRNS from those with SSNS. Received: Jan. 2023 Accepted: Jul, 2023 Published: Oct.2023

Early Diagnostic Value of KIM-1, NGAL, and NLR in Acute Kidney Injury Caused by Diquat Poisoning

Background. The kidney is the main excretory organ after diquat absorption. Acute kidney injury (AKI) is a common complication in diquat poisoning patients. Objectives. To identify the value of combined detection of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and neutrophil-lymphocyte ratio (NLR) in the early diagnosis of diquat-induced AKI. Materials and Methods. The retrospective cohort study included 42 diquat poisoning patients. Results. Forty-two patients with diquat poisoning were included, of which 20 had fulminant poisoning (47.6%). At admission (0 h), levels of KIM-1, NGAL, NLR, and acute physiology and chronic health evaluation (APACHE) II scores in the fulminant poisoning group were higher than that of the moderate to severe poisoning group ( P &lt; 0.05), and they were all higher than in the control group ( P &lt; 0.05), while blood urea nitrogen (BUN) and uric acid (UA) levels did not significantly differ across the three groups ( P &gt; 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores of patients in the fulminant poisoning group were higher than those in the moderate to severe poisoning group ( P &lt; 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( P &lt; 0.05). Among 42 patients with diquat poisoning, 28 had AKI (66.7%). At 0 h, the AKI group had higher levels of KIM-1, NGAL, NLR, and APACHE II scores than in the non-AKI (NAKI) group ( P &lt; 0.05), while there was no significant difference in BUN and UA levels between the two groups ( P &gt; 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores in the AKI group were higher than those in the NAKI group ( P &lt; 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( P &lt; 0.05). KIM-1, NGAL, and NLR are independent risk markers for AKI in diquat poisoning patients. At admission (0 h), the combined application of KIM-1, NGAL, and NLR’s sensitivity, specificity, and area under the curve (AUC) for predicting AKI in diquat poisoning patients was 0.893, 0.859, and 0.903, respectively. Conclusions. KIM-1, NGAL, and NLR can be employed as early diagnostic indicators for the clinical prediction of AKI in diquat poisoning patients. Our findings may help clinicians reduce the occurrence of AKI.

Correlation of urinary neutrophil gelatinase-associated lipocalin levels as an early diagnostic marker for acute kidney injury in patients with sepsis

Background. The exact association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and acute kidney injury (AKI) is unknown in a critical care setting, in which the population is heterogeneous and the aetiology of AKI is unclear. Aim of this study is to clarify if uNGAL level is an early diagnostic marker for AKI in patients with sepsis. Materials and methods. The current study was conducted on 86 sepsis patients. The prevalence of AKI was identified among them. The role of uNGAL in predicting AKI development, mortality rate and length of the intensive care unit (ICU) stay were analyzed. Sensitivity and specificity were calculated, and the area under the receiver operating characteristic curve was considered as the optimal uNGAL cut-off level for detecting all classifications of AKI. Results. Most patients belonged to the age group of 51–60 years and their mean age was 54.6 years. Most patients (65.11 %) were males. 26.75 % had both type 2 diabetes mellitus and hypertension. AKI was detected in 89 % of subjects in the current study, as per KDIGO definition. 15.12 % of patients had stage 1 CKD, 15.12 % had stage 2 CKD, and stage 3 CKD was diagnosed in 4.65 % of cases. Mortality rate was 11 %, and 89 % of patients were discharged. The mean ICU length of stay among patients with AKI is 8.9 days. There is significant association between the mean ICU length of stay and AKI presence (p = 0.03). 17.4 % (n = 15) of patients required renal replacement therapy. There is a very significant difference in mean baseline uNGAL in patients with and without AKI: 149.9 and 73.2 ng/ml, respectively (p = 0.0006). This indicated that baseline uNGAL levels predict AKI. The mean uNGAL in people with AKI was 356 ng/ml and in those without AKI, it was 95 ng/ml. There is a very significant difference in mean uNGAL 48 hours after in patients with and without AKI (p &lt; 0.0001). At a cut-off value of 120, there were 69 true positive cases, 9 true negative cases, 0 false positive cases, and 8 false negative cases. Based on these, the sensitivity of uNGAL at baseline in detecting AKI is 89.61 %, specificity is 100 %, and accuracy is 90.70 %. At a cut-off point of 120, there were 77 true positive cases, 8 true negative cases, 1 false positive case, and 0 false negative cases. Based on these, the sensitivity of uNGAL 48 hours after was 100 %, specificity 88.89 %, and accuracy was 98.84 %. There is a significant association between uNGAL levels and the ICU length of stay (p = 0.00). Conclusions. Sensitivity analysis was done in cut-off value of 120 for urinary NGAL in predicting AKI. From these results we conclude that urinary NGAL at the time of ICU admission is a reliable marker of renal function in sepsis patients. There is a significant correlation between AKI presence and urinary NGAL, and the ICU length of stay. We recommend not to use uNGAL alone in predicting AKI. It should be combined with glomerular filtration rate to reliably detect AKI development. Study findings indicate that sepsis patients with elevated uNGAL require proper management with close monitoring of blood pressure, urine output and appropriate doses of diuretics to avoid the development of AKI.

Evaluation of Lac and NGAL on the Condition and Prognosis of Patients with Diquat Poisoning.

This study aims to explore the evaluation of lactic acid (Lac) and neutrophil gelatinase-associated lipocalin (NGAL) on the condition and prognosis of patients with diquat (DQ) poisoning. A total of 79 cases of DQ poisoning treated in one hospital from January 2019 through February 2023 were included: 10 cases of mild poisoning, 49 cases of moderate to severe poisoning, and 20 cases of fulminant poisoning. According to the Kidney Disease: Improving Global Outcomes-acute kidney injury (KDIGO-AKI) criteria, the patients were divided into 60 cases in the AKI group and 19 cases in the non-acute kidney injury (NAKI) group. According to the AKI diagnostic indicators, AKI patients were divided into Grade I, Grade II, and Grade III. According to prognosis, the patients were divided into survivor group and non-survivor group. During the same period, 30 healthy subjects were selected as the healthy group. The changes of blood Lac, NGAL, cystatin C (CysC), and serum creatinine (Scr) levels of patients were detected, the 28-day survival of patients was recorded, and the correlation between blood Lac, NGAL levels, and renal injury grade in patients with AKI caused by DQ poisoning was analyzed. The receiver operator characteristic (ROC) curve was used to evaluate the predictive value and prognostic value of Lac, NGAL, and their combination in patients with AKI caused by DQ poisoning. There were significant differences in AKI grade, Lac, NGAL, CysC, and Scr levels among different degrees of poisoning groups (P < .05). There were significant differences in the levels of Lac, NGAL, CysC, and Scr among patients with different AKI grades (P < .05). The levels of Lac, NGAL, CysC, and Scr in the survivor group were significantly lower than those in the non-survivor group (P < .05). The blood Lac and NGAL levels were positively correlated with AKI grades in patients with DQ poisoning (r = 0.752, 0.836; P = .000, .000). The combined detection of blood Lac and NGAL had higher predictive value for AKI and assessed value for death in DQ poisoning than either of them alone. The combined detection of Lac and NGAL have a certain clinical value in AKI grading and evaluating AKI prognosis caused by DQ poisoning.

Endothelial Injury in Paediatric Sepsis-associated Acute Kidney Injury

Background: Sepsis-associated acute kidney injury (SA-AKI) is an acute kidney injury in the presence of sepsis without other significant contributing factors explaining acute kidney injury (AKI). Circulating syndecan-1, angiopoietin-2, and urinary neutrophil gelatinase-associated lipocalin levels can potentially cause neglected AKI to become acute kidney disease (AKD) and even chronic kidney disease (CKD). Therefore, studying its levels in the early phase of AKI is important, especially in SAAKI. Objectives: This study aims to analyze the levels of syndecan-1, angiopoietin-2, and urine neutrophil gelatinase-associated lipocalin (uNGAL) as other modalities that might detect AKI earlier in children with SAAKI. Methods: This study enrolled 23 children between one month and 18 years with sepsis. Blood samples were collected from all patients at the baseline, 12, 24, and 48 hours after admission to assess serum creatinine, syndecan-1, angiopoietin-2, and a urine sample was collected to measure uNGAL levels. We used the Wilcoxon signed-rank test to compare each biomarker with the time of measurement and the Mann-Whitney test to compare the levels of biomarkers with the incidence of SA-AKI. Results: The highest median value for uNGAL was 78.30 (3.20 - 24098.40) in the 12th-hour measurement; for syndecan was 2.92 (0.06 - 83.00) in the baseline measurement, slightly decreased and continued to increase up to 48 hours, and for Ang-2 was 4159.60 (17.60 - 226428.00) in the 12th-hour measurement. The incidence of SA-AKI based on the pediatric risk-injury-failure-loss-end stage (pRIFLE) criteria were that five children (21.7%) had AKI in the risk/injury phase at baseline, 24-hour, 48-hour observations, and also six children (26.1%) at 12-hour observation. Conclusion: There was an increase in levels of syndecan-1 and ang-2 in children with severe sepsis, especially in the first 24 hours.

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

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

Significance of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) for the Monitoring of Treatment Response to Cyclosporine in Patients with Psoriasis.

Serum samples were obtained before and after three months cyclosporine therapy. Patients were grouped into responders and non-responders to cyclosporine depending on whether they achieved at least 50% reduction of Psoriatic Activity Score Index (PASI), or not. Serum levels of PCSK9 and NGAL were assayed using commercially available ELISA tests. Lipid levels were measured with an enzymatic method. There were 40 patients enrolled. A significant decrease in serum NGAL level was seen in cyclosporine responders. No similar dependance was found for PCSK9. Serum PCSK9 concentration correlated with total cholesterol (TChol) and LDL at baseline and after three month treatment. Cyclosporine therapy contributes to the reduction of the NGAL serum but not the PCSK9 concentration. Correlation between the PCSK9 serum level and TChol as well as LDL concentration may help to understand drug induced dyslipidemia after cyclosporine.

Neutrophil gelatinase-associated lipocalin: function, specificity, role in the diagnosis of renal dysfunction in hypertensive patients with concomitant type 2 diabetes and obesity

Background. Neutrophil gelatinase-associated lipocalin (NGAL) belongs to the superfamily of lipocalins whose main function is the binding and transportation of hydrophobic molecules, si­derophores, as the most important ligands of NGAL. The diagnostic significance of NGAL as a marker of renal dysfunction, as well as its prognostic value in terms of the further prognosis of the course of renal pathology has now been confirmed. The purpose of the study: to determine the role of NGAL in the development of renal dysfunction in hypertensive patients with comorbid type 2 diabetes (T2D) and obesity. Materials and methods. One hundred and eleven patients with hypertension (50 men, 61 women) aged 54.37 ± 1.18 years and 20 controls were examined. During the examination, they were divi­ded into 4 groups depending on the presence of comorbid pathology: hypertension — the first group (n = 22); hypertension combined with obesity — the second group (n = 30); hypertension combined with T2D — the third group (n = 31); hypertension, T2D and obesity — the fourth group (n = 28). In all patients, body weight and height were measured, body mass index was calculated, levels of glycated hemoglobin, lipid metabolism, systolic and diastolic blood pressure were measured. The content of NGAL in blood serum was evaluated by the enzyme-linked immunosorbent assay. Results. The level of NGAL in all patients included in the study was significantly higher compared to the control group (p &lt; 0.01). However, it was highest in comorbidity of hypertension, T2D and obesity, which, in turn, indicates a high risk of interstitial fibrosis in these patients. A significant correlation was found between the level of NGAL and the concentration of cardiotrophin (p &lt; 0.032), catestatin (p &lt; 0.001), β2-microglobulin (p &lt; 0.001), cystatin (p &lt; 0.021), atherogenic coefficient (p &lt; 0.011), NT-proBNP (p &lt; 0.014), vitamin D (p &lt; 0.004). The obtained data demonstrate the significant role of NGAL in the development of early cardiovascular and renal complications in our patients. Conclusions. A significant increase in the level of NGAL was found in patients with hypertension, hypertension with T2D, hypertension with obesity, hypertension with T2DM and obesity compared to healthy individuals (p &lt; 0.01). A significant correlation of the NGAL level with the serum concentration of cardiotrophin, catestatin, cystatin C, β2-microglobulin, atherogenic coefficient, NT-proBNP, and vitamin D in the exami­ned patients was proved.

Sputum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Asthma-COPD Overlap.

Asthma COPD overlap (ACO) is a consensus-based phenotype having characteristics of both COPD and asthma. Distinguishing ACO from other diseases is even more important as it is related to low health-related quality of life, augmented exacerbation rate and hospital admission, a rapid deterioration in lung function, and increased morbidity and mortality. But it cannot be diagnosed explicitly based on spirometry tests, patient demographics, radiology, or by-sputum cytology. There is an unmet need to develop biomarkers. To assess the role of sputum neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of ACO. To find the correlation between sputum NGAL levels with forced expiratory volume 1 (FEV1) and exacerbation rate in ACO. To find the correlation between sputum NGAL level with sputum neutrophils and eosinophils in ACO. In this comparative correlational study, 180 subjects were enrolled into four groups with 45 patients each with asthma, COPD, ACO, and healthy nonsmokers respectively, respectively. After taking detailed history and demographics, sputum was analyzed for the differential count and NGAL. Asthma COPD overlap (ACO) cases had high sputum NGAL levels; the second was the COPD group, and the last in the case asthma group. Nonsmokers had notably lower readings than the diseased. Out of three, receiver operating characteristic (ROC) figures, the validity of NGAL was best in selecting patients of ACO than COPD and asthma. The area under curve (AUC) was highest for ACO and less than the acceptable limit for the remaining two. NGAL cut-off value of 2473 pg/mL had 80% sensitivity and 50% specificity for ACO. The present study investigated the sputum NGAL levels as a biomarker in ACO identified by the syndromic approach. Sputum NGAL, a biomarker associated with airway inflammation in airway diseases, was supportive of clinically differentiating ACO from asthma to COPD. How to cite this article: Babu A, Narayanswamy H, Baburao A. Sputum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Asthma-COPD Overlap. J Assoc Physicians India 2023;71(9):34-38.

Denervation aggravates renal ischemia reperfusion injury via BMAL1-mediated Nrf2/ARE pathway

AimTo explore the change of clock gene rhythm under renal denervation (RDN) and its effect on renal function and oxidative stress during renal ischemia-reperfusion (IR) injury. MethodC57/BL6 mice were randomly divided into 4 groups at daytime 7 A M (zeitgeber time [ZT] 0) or at nighttime 7 P M (ZT12) in respectively: Sham (S) group, RDN group, IR group and RDN + IR (DIR) group. Renal pathological and functional changes were assessed by H&E staining, and serum creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin levels. Renal oxidative stress was detected by SOD and MDA levels, and renal inflammation was measured by IL-6, IL-17 A F and TNF-ɑ levels. BMAL1, CLOCK, Nrf2 and HO-1 mRNA and protein expressions were tested by qPCR and Western Blot. ResultCompared with S groups, the rhythm of BMAL1, CLOCK and Nrf2 genes in the kidney were disordered in RDN groups, while renal pathological and functional indexes did not change significantly. Compared with IR groups, renal pathological and functional indexes were significantly higher in the DIR groups, as well as oxidative stress and inflammation in renal tissues. The nocturnal IR injury in the RDN kidney was the worst while the BMAL1, Nrf2 and HO-1 expressions were the highest. In DIR groups, renal injury was aggravated after the Brusatol treatment, but there was no significant improvement after the t-BHQ treatment at night, which might be consistent with the changes of Nrf2 and HO-1 protein expressions. ConclusionRDN lead to the disruption of BMAL1-mediated Nrf2 rhythm accumulation in the kidney, which reduced the renal ability to resist oxidative stress and inflammation, due to the impaired effect of activating Nrf2/ARE pathway in renal IR injury at nighttime.

Neutrophil Gelatinase Associated Lipocalin: A Possible Role in β Thalassemia Syndromes

Abstract Background Beta Thalassemia is a group of inherited blood disorders that caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable outcomes ranging from severe anaemia to clinically asymptomatic individuals. Neutrophil gelatinase-associated lipocalin (NGAL), is a protein which is encoded by the LCN2 gene. NGAL is involved in innate immunity by sequestrating iron that in turn limits bacterial growth. It is expressed in neutrophils and in low levels in the kidney, prostate, and epithelia of the respiratory and the alimentary tracts. It also plays a key role in the physiology and pathophysiology of red blood cells, particularly in anemia. Aim of the Work The aim of the present work is to assess plasma level of NGAL in Beta thalassemia syndromes and correlate with laboratory hematological data and iron profile. Patients and Methods A Case-Control study conducted on Beta Thalassemia patients of both sexes attending the outpatient clinic of Ain Shams University Hospitals, this Pilot study of 50 previously diagnosed Beta Thalassemia patients and 30 sex and age matched healthy control subjects. Results The results were correlated with clinical and laboratory parameters. Comparative analysis of the results showed that all groups were homogeneous in terms of size and demographic characteristics. This can explain our results that shows that there is a highly statistically significant difference (p-value &amp;lt; 0.001) between the cases subgroups regarding the inter-transfusion interval with longer intervals among the thalassemia intermedia subgroup. While by comparing the Hb electrophoresis parameter between the 2 groups HbA% levels were higher is the group of serum ferritin &amp;lt;1000 ng/ml and HbF% where higher in group of serum ferritin &amp;gt;1000 ng/ml with (p-value &amp;lt; 0.05) for both of them. On conducting a linear regression analysis we found that the intertransfusion interval was the only independent parameter to have an effect on NGAL level on our patient group with regression coefficient -5.78 and this complies with our results of correlation between NGAL and those parameters mentioned and discussed previously. Conclusion The relationship between NGAL and iron level in Egyptian β-TM patients proved in our results has confirmed the proposed regulatory role played by NGAL on erythropoiesis and iron metabolism in β-thalassemia, NGAL at a cutoff value of &amp;gt; 100 proved to be an efficient predictor of increased serum ferritin &amp;gt; 1000 ng/ml. we believe that incorporating NGAL testing in the work up of β-TM patients in the early phases of iron transfusion dependency would provide a promising sensitive and predictive tool for early iron accumulation. We recommend further studies β-TM patients with larger samples size to clarify the co-regulatory role of erythropoiesis and iron metabolism played by NGAL.

Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic UTI patients aged ≥ 60 years and correlated them with detected levels of the immune response biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-8), and interleukin-1-beta (IL-1β). The objective was to identify the microbial densities associated with significant elevation of these biomarkers in order to determine an optimal threshold for diagnosing symptomatic UTIs. Biobanked midstream voided urine samples were analyzed for microbial identification and quantification using standard urine culture (SUC) and multiplex-polymerase chain reaction (M-PCR) testing, while NGAL, IL-8, and IL-1β levels were measured via enzyme-linked immunosorbent assay (ELISA). NGAL, IL-8, and IL-1β levels were all significantly elevated at microbial densities ≥ 10,000 cells/mL when measured via M-PCR (p < 0.0069) or equivalent colony-forming units (CFUs)/mL via SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable than 100,000 CFU/mL for diagnosing UTIs.