Plasma Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

Ratlarda Oluşturulan Renal İskemi Reperfüzyon Hasarında Epibatidinin Etkileri

Objective: The attenuation of renal ischemia reperfusion (I/R) injury by stimulating cholinergic antiinflamatory pathway has been demonstrated in the literature. The purpose of this study is to investigate the protective effects of epibatidine, a non selective nicotinic acethycholine receptor agonist, administered before ischemia on renal ischemia-reperfusion injury. Methods: After Ethics Committee approval, 24 Wistar Albino rats were randomly allocated into 4 groups. Group S: Sham (n=6), Group I/R: Ischemia/reperfusion (n=6), Group I/R-E: Ischemia/ reperfusion-Epibatidine (n=6), Group E: Epibatidine (n=6). All groups underwent laparotomy and bilateral renal artery and vein dissection under anesthesia. No further action was taken in Group S. In Group I/R and Group I/R-E, renal ischemia was applied for 25 minutes and then reperfusion for 24 hours. A single dose of 5 μg kg-1 epibatidine was administered subcutaneously before the laparotomy in Group I/R-E and Group E. At the end of the reperfusion period, blood and urine samples were taken for plasma BUN, creatine, plasma and urinary neutrophil gelatinase associated lipocalin (NGAL) and cystatin C, plasma IL-6 and TNF-α assessment. Results: Plasma BUN, creatine, NGAL, cystatin C, IL-6 and TNF-α levels were significantly higher in Group I/R when compared to Group S (p<0.05). All the levels of the above biomarkers were comparable in Group S and Group I/R-E. Conclusion: These results indicate that epibatidine administration before ischemia has a protective effect on kidney in renal I/R injury induced rats. Keywords: Renal ischemia-reperfusion injury, cholinergic antiinflammatory pathway, n7AchR, epibatidine, NGAL

Plasma NGAL (Neutrophil Gelatinase Associated Lipocalin) Levels in Septic Patients With & Without Acute Kidney Injury: A Plausible Biomarker

Introduction: Acute kidney injury is extremely common among septic patients. Its early recognition among critically ill patients can help in better prognosis and decrease the risk of longer hospital stay and dialysis requirement. Creatinine is considered as a gold standard for diagnosis of Acute Kidney Injury but it has its own disadvantages. New biomarkers for Acute Kidney Injury that can help in its early recognition are the need of time. Many plasma and urinary markers including Neutrophil Gelatinase Associated Lipocalin are being studied. Its role in earlier detection of septic Acute Kidney Injury in septic patients in our set of population still needs extensive research where incidence of sepsis associated complications leading to death is extremely high. Aims and Objectives: To measure plasma Neutrophil Gelatinase Associated Lipocalin levels in septic patients with and without acute injury compare pNGAL levels in two groups, and to measure specificity and sensitivity of plasma Neutrophil Gelatinase Associated Lipocalin levels in both sets of patients. Place and Duration of study: A cross sectional analytical study was carried out in National Health Research Complex, Shaikh Zayed Hospital, Lahore over a period of 3 years from 2016-2019 Material and Methods: This is a cross-sectional analytical study carried out in ninety two patients that are divided in two groups on the basis of creatinine levels measured at 72hrs. First group consists of septic patients who developed Acute Kidney Injury (AKI) and second group consists of septic patients Without Acute Kidney Injury(WAKI). Plasma NGAL levels are compared in two groups. SPSS v 20 was used for analysis, p-value ? 0.05 was considered significant. Results: The plasma NGAL level at 24 hours for group without Acute Kidney Injury was 126.4±15.4 ng/ml and for the group which developed Acute kidney Injury was 191.1±15.9 ng/ml and the difference was clearly significant with p- value <0.001. Conclusion: pNGAL levels are significantly raised than the cut-off value of 150ng/ml at 0hrs in septic patients who developed AKI as compared to septic patients who didn’t develop AKI.

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.

Plasma neutrophil gelatinase-associated lipocalin role as a developing biomarker of acute renal failure following coronary artery bypass surgery

Introduction: Acute kidney injury (AKI) following coronary artery bypass graft (CABG) procure is related with elevated morbidity and mortality, early diagnosis of which is important for effective management of these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted glycoprotein in response to inflammation. Objectives: The current study aimed to evaluate the role of serum NGAL in predicting AKI in a group of Iranian patients undergoing CABG. Patients and Methods: This study was a cross-sectional prospective study conducted on 79 patients undergoing CABG from Mousavi hospital, Zanjan, Iran. The blood samples for serum creatinine and plasma NGAL levels were collected before anesthesia induction and at 12th, 24th and 48th hour’s post-operative. The plasma NGAL level was measured using enzyme-linked immunosorbent assay method. The incidence of AKI was known by the risk-injury-failure-loss-end-stage renal disease (RIFLE) criteria. Results: In 23 cases (29%) AKI development was detected. In a 24-hour follow-up, the mean serum creatinine values did not change in patients while the mean plasma NGAL level was elevated within 12 hours post-operatively (207.2±180.8 ng/mL and 119.26±103.5 ng/mL in the AKI and non-AKI groups, respectively). The plasma NGAL level measured after CABG (with the cut-off point equal to 126.4 ng/mL) showed a sensitivity of 77% and a specificity of 81% for the prediction of AKI. In AKI group, no patient had grade 3 AKI and neither required dialysis. Conclusion: These data indicated that the plasma NGAL levels could be potentially utilized for early diagnosis of AKI in patients undergoing CABG.

#5267 INITIAL EMERGENCY ROOM 6-HOUR URINE VOLUME IS AN IMPORTANT FACTOR FOR THE SURVIVAL OF CRITICALLY ILL PATIENTS UNDERGOING CRRT

Abstract Background and Aims It has been little known whether initial emergency room factors affect survival or renal function in critically ill patients undergoing continuous renal replacement therapy. We examined whether initial factors in ER impact survival and renal recovery in critically ill patients undergoing continuous renal replacement therapy. Method The study was a single-center, retrospective study of 332 patients for critically ill patients admitted to ICUs for continuous renal replacement therapy via emergency room from March 1, 2018 to May 31, 2021. Clinical parameters including urine output, eGFR, and serum NGAL were identified. The primary outcomes were the 30-day and 90-day mortality. Secondary outcomes were the 30-, and 90-day dialysis-free duration. Results Low urine output (LUO, defined as &amp;lt; 0.5 mL/kg/hr x 6 hours) group was significantly associated with 30-day mortality and 90-day mortality. Multivariable Cox regression analysis showed that LUO group was significantly more associated with the increased risk of 30-day mortality and 90-day mortality (hazard ratio, 1.935 and 2.141, respectively) compared to high urine output (HUO, defined as ≥ 0.5 mL/kg/hr x 6 hours) group. There was no significant association between 30-day or 90-day mortality and initial estimated glomerular filtration rate (eGFR) plasma neutrophil gelatinase-associated lipocalin (NGAL) levels. In critically ill patients undergoing continuous renal replacement therapy, HUO group and initial eGFR ≥ 30 ml/min/1.73m2 groups was associated with decreased 30-, and 90-day dialysis-free duration. However, serum NGAL had no significant relation with 30-, and 90-days RRT free durations. Conclusion During admission to emergency room, the initial low urine output is an important factor for 30-day and 90-day mortality in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

Circulating mitochondrial dysfunction as an early biomarker for contrast media-induced acute kidney injury in chronic kidney disease patients.

Contrast-induced acute kidney injury (CI-AKI) is the common hospitalized acute kidney injury (AKI). However, the diagnosis by serum creatinine might not be early enough. Currently, the roles of circulating mitochondria in CI-AKI are still unclear. Since early detection is crucial for treatment, the association between circulating mitochondrial function and CI-AKI was tested as a potential biomarker for detection of CI-AKI. Twenty patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) were enrolled. Blood and urine samples were obtained at the time of PCI, and 6, 24, 48 and 72 h after PCI. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured. Oxidative stress, inflammation, mitochondrial function, mitochondrial dynamics and cell death were determined from peripheral blood mononuclear cells. Forty percent of patients developed AKI. Plasma NGAL levels increased after 24 h after receiving contrast media. Cellular and mitochondrial oxidative stress, mitochondrial dysfunction and decreased mitochondrial fusion occurred at 6 h following contrast media exposure. Subgroup of AKI had higher %necroptosis cells and TNF-α mRNA expression than subgroup without AKI. Collectively, circulating mitochondrial dysfunction could be an early predictive biomarker for CI-AKI in CKD patients receiving contrast media. These findings provide novel strategies to prevent CI-AKI according to its pathophysiology.

Diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for detection of renal failure in hypertensives: a case–control study in a regional hospital in Ghana

BackgroundRenal failure is one of the most serious vascular effects of hypertension. For better therapy and prevention of complications, early kidney disease identification in these patients is absolutely essential. However, current studies have proposed plasma Neutrophil Gelatinase Associated Lipocalin (pNGAL) to be a better biomarker comparative to serum creatinine (SCr). This study assessed the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a biomarker for early nephropathy diagnosis in hypertensive individuals.MethodsThis hospital-based case–control study comprised 140 hypertensives and 70 healthy participants. A well-structured questionnaire and patient case notes were used to document relevant demographic and clinical information. 5 ml of venous blood sample was taken to measure fasting blood sugar levels, creatinine, and plasma NGAL levels. All data were analyzed using the Statistical Package for Social Sciences (SPSS release 20.0, copyrite©SPSS Inc.) and a p-value < 0.05 was considered statistically significant.ResultsIn this study the plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in cases compared to controls. Hypertensive cases also had significantly higher waist-circumference compared to the control group. The median fasting blood sugar level was significantly higher in cases compared to controls. This study established the use of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft and Gault formula (CG) as the most accurate predictive equations for assessing renal dysfunction. The threshold for NGAL above which renal impairment can be assessed was found to be 109.4 ng/ml (sen-91%, spec. – 68%), 120 ng/ml (sen- 100%, spec- 72%) and 118.6 ng/ml (sen- 83%, spec- 72%) for MDRD, CKD-EPI and CG equations respectively. The prevalence of CKD was 16.4%, 13.6% and 20.7% respectively using the MDRD, CKD-EPI and CG.ConclusionFrom this study, pNGAL is a better indicator of kidney impairment in the early stages of CKD as compared with sCr in general hypertensive population.

Evidence of kidney injury in preeclampsia: Increased maternal and urinary levels of NGAL and KIM-1 and their enhanced expression in proximal tubule epithelial cells.

Proteinuria and glomerular endotheliosis are characteristics of glomerular injury in preeclampsia, a hypertensive disorder in human pregnancy. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are biomarkers of acute/chronic renal tubule injury. To determine if tubule injury occurs in preeclampsia, we determined maternal plasma and urine NGAL and KIM-1 levels and evaluated NGAL and KIM-1 expression in kidney biopsy specimens from women with preeclampsia. Prenatal and postpartum maternal blood and urinary samples were collected from three groups of pregnant women: normal pregnancy (n = 100), preeclampsia (n = 83), and pregnancy complicated with chronic hypertension (n = 20). Plasma and urine levels of NGAL and KIM-1 were measured by ELISA. Kidney biopsy tissue sections from patients with preeclampsia (n = 5) were obtained from Pathology Archives and processed to determine NGAL and KIM-1 expression by immunostaining and high kidney solution images were assessed by electron microscopy (EM). Prenatal plasma and urine levels of NGAL and KIM-1 were significantly higher in preeclamptic than in normal controls, p < 0.01. In normal pregnancy, both plasma and urine levels of NGAL and KIM-1 at 24-48 h after delivery and 6-8 weeks postpartum were relatively comparable to that of antenatal levels. In preeclampsia, urine, but not plasma, NGAL levels were reduced at 6-8 weeks postpartum compared to the antenatal levels, p < 0.05. Although maternal and urine KIM-1 levels were reduced at 6-8 weeks postpartum compared to the antenatal levels in preeclampsia, the levels were still higher than those in normal pregnancy. Positive expression of NGAL and KIM-1 was detected in proximal tubule epithelial cells in kidney tissue specimens from preeclampsia but not in non-pregnancy controls. EM examination showed glomerular and tubular injury in preeclampsia. Our findings of increased maternal levels and urine secretion of NGAL and KIM-1, along with the upregulation of NGAL and KIM-1 expression in tubular epithelial cells in preeclampsia, provide plausible evidence that tubular injury exists in preeclampsia. The higher postpartum NGAL and KIM-1 levels in preeclamptic pregnancies indicate that tubular injury would not resolve within 2-3 months after delivery and suggest that proper follow-up and management of kidney function in women with preeclampsia would be necessary to reduce chronic kidney diseases in those women later in life.

L-FABP and NGAL are novel biomarkers for detection of abdominal injury and hemorrhagic shock

IntroductionDelayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries. Patients and MethodsTraumatized patients with an age ≥18 years and an abdominal injury (AISabd≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury (“Abd”) and 10 patients had an abdominal injury with hemorrhagic shock (“HS Abd”). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 (“noAbd”) were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. ResultsAll patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in “HS Abd” group (1209.2 ng/ml [IQR=575.2–1780.3]) compared to “noAbd” group (36.4 ng/ml [IQR=14.8–88.5]), and to “Abd” group (41.4 ng/ml [IQR=18.0–235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group “Abd” were significantly higher (108.3 ng/ml [IQR=31.4–540.9]) compared to “noAbd” (26.4 ng/ml [IQR=15.5–88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in “HS Abd” group (115.9 ng/ml [IQR=90.6–163.8]) compared to “noAbd” group (58.5 ng/ml [IQR=41.0–89.6],p<0.001) and “Abd” group (70.5 ng/ml [IQR=53.3–115.5], p<0.05). The group “Abd” showed significant higher median NGAL levels compared to “noAbd”, p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. Conclusion:L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same.

Evaluation of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early diagnostic marker of acute kidney injury (AKI) in critically ill trauma patients.

Acute kidney injury (AKI) is a frequent complication of severe trauma associated with high mortality. The aim of this study was to evaluate the diagnostic ability of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of AKI assessed by RIFLE criteria as reference in trauma patients in intensive care unit (ICU). This was a prospective observational study. Four hundred and eighteen patients admitted in the trauma ICU with age ≥18 years without known renal diseases were followed-up (serum creatinine, urine output, and estimated glomerular filtration rate) for 5 consecutive days. As per RIFLE criteria, 70 patients were broadly classified as AKI and rest of the patients (n = 348) as non-AKI. Plasma and urine samples of AKI (n = 70) and non-AKI (n = 70) patients were further assessed for 3 consecutive days following admission. Mean plasma NGAL (pNGAL) was significantly elevated in AKI patients as compared with non-AKI patients; on admission: 204.08 versus 93.74 ng/mL (P = 0.01); at 24 h: 216.73 versus 94.63 ng/mL (P = 0.01); and 48 h: 212.77 versus 86.32 ng/mL (P = 0.01). Mean urine NGAL (uNGAL) at 48 h was also significantly elevated: 15.45 ng/mL in AKI patients as compared with 13.48 ng/mL in non-AKI patients (P = 0.01). Plasma and urine NGAL levels were significantly associated with increased mortality. pNGAL had good predictive value on admission (area under the receiver operative characteristic [AUROC] 0.84), at 24 h (AUROC 0.88) and 48 h (AUROC 0.87), while uNGAL had moderate performance at 24 h (AUROC 0.61) and 48 h (AUROC 0.71). pNGAL can be used as an early and potent diagnostic and predictive marker of AKI and mortality in critically ill trauma patients.

Upregulation of Myocardial Neutrophil Gelatinase-Associated Lipocalin during Development of Heart Failure Caused by Volume-Overload and the Effect in Regulating Activity of Matrix Metalloproteinase-9.

In patients with heart failure (HF), circulating neutrophil gelatinase-associated lipocalin (NGAL) level is increased, which is considered to be a predictor of mortality or renal outcomes. The expression of NGAL in the heart and kidney and its role in HF remain unclear. Aortocaval fistula was created in rats as a model of volume overload (VO)-induced HF. During the development of HF, NGAL expression was upregulated in the heart but not in the kidney at both transcriptional and translational levels in the compensatory and HF phases, with a similar level in both phases. Cardiomyocytes were identified as the cell type responsible for NGAL expression. Consistent with the myocardial NGAL expression pattern, the plasma NGAL level was increased in both phases, and the level was not significantly different between both phases. We demonstrated the presence of a matrix metalloproteinase (MMP)-9/NGAL complex in cultured medium of cardiomyocytes isolated from volume-overloaded hearts by gelatin zymography. Formation of MMP-9/NGAL complex was shown to enhance the enzymatic activity of MMP-9. We found that early growth response (Egr)-1 was upregulated in the heart in both compensatory and HF phases. In neonatal cardiomyocytes, Egr-1 overexpression induced the gene expression of NGAL, which was dose-dependently suppressed by an interleukin-1 receptor antagonist. During the development of HF due to VO, NGAL was upregulated in the heart but not in the kidney in both compensatory and HF phases, with a similar expression level. Myocardial NGAL upregulation enhanced MMP-9 activity through formation of the MMP-9/NGAL complex. The expression of myocardial NGAL was regulated by Egr-1.

Neutrophil Gelatinase-Associated Lipocalin as Potential Predictive Biomarker of Melanoma and Non-Melanoma Skin Cancers in Psoriatic Patients: A Pilot Study.

Background: Studies have demonstrated a higher risk of nonmelanoma skin cancers (NMSC) and a modestly increased melanoma risk in patients with psoriasis. To date, no biomarkers predictive of evolution have been identified yet. Methods: The aim of this prospective case-control study was to investigate the potential role of neutrophil gelatinase-associated lipocalin (NGAL) as a predictive biomarker of skin cancers in psoriatic patients. Patients with a diagnosis of psoriasis were enrolled, as well as healthy subjects and patients with skin cancers as controls. Plasma protein expression of NGAL, metalloproteinases (MMP)-2, and MMP-9 was performed by an enzyme-linked immunosorbent assay (ELISA). In all the patients who developed skin cancer at follow-up, NGAL, MMP-2, and MMP-9 serum levels were dosed again. Results: Plasma NGAL levels were significantly higher in psoriatic patients with NMSC than without (182.3 ± 36.6 ng/mL vs. 139.9 ± 39.3 ng/mL) (p < 0.001). Plasma NGAL levels were significantly higher (p < 0.00001) in patients with psoriasis and NMSC than in patients with skin tumors without psoriasis (182.3 vs. 122.9). Patients with psoriasis who developed NMSC at follow-up showed increased plasma MMP-9 levels. Conclusion: NGAL seems to play a role in the pathogenesis of NMSC but not melanoma in patients with psoriasis.

Elevation of neutrophil carcinoembryonic antigen-related cell adhesion molecule 1 associated with multiple inflammatory mediators was related to different clinical stages in ischemic stroke patients.

BackgroundWe aimed to analyze the level of carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) in neutrophils of ischemic stroke (IS) patients at different stages, together with its roles in neutrophils.Patients and methodsSixty‐seven patients were classified into acute phase group (n = 19), subacute phase group (n = 28), and stable phase group (n = 20), and 20 healthy individuals who had received physical examination at the same time period as healthy control. We then analyzed the expression level of CEACAM1 and cell viability in CEACAM1 positive and CEACAM1 negative neutrophils by flow cytometry and the content of plasma CEACAM1, neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinases‐9 (MMP‐9) was measured using enzyme‐linked immunosorbent assay (ELISA), while that of interleukin‐10 (IL‐10) and tumor necrosis factor (TNF) was determined using a Human Enhanced Sensitivity Flex set.ResultsCompared with healthy control, the percentage of CEACAM1 positive neutrophils in IS patients showed a significant increase, and a significant increase was also noticed in the content of plasma CEACAM1 at the subacute stage. Reduction in cell viability was observed in CEACAM1 positive neutrophils compared with CEACAM1 negative counterparts. There was a positive correlation between CEACAM1 expression rate in neutrophils and plasma CEACAM1 and IL‐10 content in the subacute group. Compared with acute group and healthy control group, there was an instinct increase in the level of plasma MMP‐9 and NGAL in subacute group.ConclusionsOur data showed that there was a rapid increase of CEACAM1 in neutrophils at the acute stage of IS. We speculated that CEACAM1 may serve as an inhibitory regulator involving in the progression of IS.

POS-068 DIAGNOSTIC VALUE OF PLASMA NEUTROPHIL GELATINASE - ASSOCIATED LIPOCALIN (NGAL) IN DISTINGUISHING ACUTE KIDNEY INJURY FROM CHRONIC KIDNEY DISEASE

Acute kidney injury (AKI) and chronic kidney disease (CKD) are conditions that substantially increase morbidity and mortality. New biomarker plasma neutrophil gelatinase –associated lipocalin (NGAL) can identify the patients with AKI and CKD earlier which helps to intervene and modify outcome.The aim of the study was to determine whether plasma NGAL levels could be used to distinguish AKI and CKD.

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.

Neutrophil Gelatinase-Associated Lipocalin as a Marker for Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention: A Prospective Observational Analysis.

Introduction:Incidence of contrast-induced nephropathy (CIN) post percutaneous coronary intervention (PCI) varies between 5% and 20%. Neutrophil gelatinase–associated lipocalin (NGAL) is a sensitive marker for acute kidney injury. Data regarding the predictive accuracy of NGAL in Indian patients undergoing PCI is sparse.Methods:A total of 212 consecutive “all-comer” patients, undergoing PCI from March 2015 to April 2016 were recruited in this single-center observational study. Plasma NGAL levels were measured at 4 hours post PCI using commercially available enzyme-linked immunosorbent assay (Triage® Alere™, San Diego, CA, USA).Results:Twenty-five (11.8%) patients developed CIN. The 4-hour post-PCI plasma NGAL levels were significantly higher in patients with CIN than without (400.6 ± 269.3 ng/mL vs. 109.8 ± 68.0 ng/mL, P < 0.0001). Patients developing CIN had higher age, low estimated glomerular filtration rate (eGFR), and higher contrast volume usage during PCI. After adjusting for confounding factors, diabetes mellitus (adjusted odds ratio [AOR] 3.04; P = 0.039; 95% confidence interval [CI]: 1.06–8.73), hypotension at presentation (AOR 24.84; P < 0.0001; 95% CI: 4.65–132.83), and multi-staged PCI (AOR 13.45; P < 0.0001; 95% CI: 4.54–39.79) were found to independently predict the development of CIN. NGAL levels significantly correlated with age (r = 0.149, P = 0.031), eGFR (r = −0.385, P < 0.0001), hemoglobin (r = −0.214, P = 0.002), contrast volume (r = 0.185, P = 0.007), and 48-hour post-PCI serum creatinine levels (r = 0.334, P < 0.0001). At a cutoff of 256.5 ng/mL, plasma NGAL had a sensitivity of 68% and a specificity of 95.2% (area under the curve = 0.878; P < 0.0001; 95% CI: 0.801–0.955) to predict the occurrence of CIN.Conclusions:Plasma NGAL is an early and highly predictive biomarker of CIN in patients undergoing PCI. Patients having diabetes, hypotension at presentation and those undergoing second-stage procedures are at a high risk of developing CIN after PCI.

Neutrophil gelatinase associated lipocalin in predicting postoperative acute kidney injury in elderly.

Elderly patients are at increased risk of developing acute kidney injury (AKI) following major surgery and rapid diagnosis is essential. This study aimed to examine the potential utility of plasma neutrophil gelatinase associated lipocalin levels in early prediction of AKI in geriatric patients undergoing laparotomic oncological surgery. This prospective single-center cohort study included 60 geriatric patients (≥ 65years of age) that underwent major oncologic surgery with laparotomy. Perioperative measurements of plasma creatinine, blood urinary nitrogen, plasma lactate, urine output, and neutrophil gelatinase associated lipocalin (NGAL) were made. Patients were followed for AKI development, which is the primary outcome measure, and predictive role of NGAL was investigated. At 48h follow-up, AKI developed in 13 patients (21.7%). Significant differences in creatinine (p < 0.001), NGAL (p < 0.001), and urine output levels (p = 0.001) were evident over time between the two groups. High NGAL measurements at 6 and 24h after surgery seem to be highly predictive of AKI development. At 6h, a plasma NGAL level greater than 71.8ng/mL has a sensitivity and specificity of 85% and 81% in predicting subsequent AKI development. Plasma NGAL levels seem to represent an early and reliable marker for AKI in elderly patients undergoing laparotomic surgery with the potential to allow early diagnosis and prevent further renal deterioration. Further confirmatory studies are warranted. The study was registered to ClinicalTrials.gov (number, NCT05030727). Elderly patients are at increased risk of postoperative acute kidney injury (AKI). This study shows that plasma neutrophil gelatinase associated lipocalin is a helpful marker to predict AKI in elderly patients undergoing laparotomic major surgery, which will allow early diagnosis and prevent further renal deterioration in this vulnerable patient group.

Neutrophil gelatinase-associated lipocalin does not originate from the kidney during reperfusion in clinical renal transplantation

BackgroundAcute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules.MethodsKidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous–arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage.ResultsSignificant renal release of LFABP [trans-renal gradient 8.4 (1.7–30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1–5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood.ConclusionsIschaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.

Association of plasma neutrophil gelatinase-associated lipocalin with parameters of CKD-MBD in maintenance hemodialysis patients.

Neutrophil gelatinase-associated lipocalin (NGAL) is not only a biomarker of kidney injury but also a bone-derived factor involved in metabolism. We aimed to explore relationships between plasma NGAL and chronic kidney disease-mineral bone disorder (CKD-MBD) parameters in maintenance hemodialysis (MHD) patients. First, a cross sectional observational study, including 105 MHD patients, was conducted to explore relationships between plasma NGAL levels and CKD-MBD parameters. Second, impact of parathyroidectomy and auto-transplantation (PTX + AT) on plasma NGAL was investigated in 12 MHD patients with severe secondary hyperparathyroidism (SHPT). According to Spearman correlation analysis, plasma NGAL levels were positively correlated with female (r = 0.243, P = 0.012), vintage (r = 0.290, P = 0.003), Klotho (r = 0.234, P = 0.016), calcium(Ca) (r = 0.332, P = 0.001), alkaline phosphatase (ALP) (r = 0.401, P < 0.001) and intact parathyroid hormone (iPTH) (r = 0.256, P = 0.008); while inversely correlated with albumin(Alb) (r = - 0.201, P = 0.039). After adjusting for age, sex, vintage, Alb and all parameters of CKD-MBD(Ca, P, lg(ALP), lg(iPTH), Klotho and fibroblast growth factor 23(FGF23)), lg(NGAL) were positively correlated with Ca (r = 0.481, P < 0.001), P (r = 0.336, P = 0.037), lg(ALP) (r = 0.646, P < 0.001) in Partial correlation analysis; further multiple linear regression analysis showed same positive associations between lg(NGAL) and Ca (β = 0.330, P = 0.002), P (β = 0.218, P = 0.037), lg(ALP) (β = 0.671, P < 0.001). During the 4-7days after PTX + AT, plasma NGAL decreased from 715.84 (578.73, 988.14) to 688.42 (660.00, 760.26) ng/mL (P = 0.071), Klotho increased from 496.45 (341.73, 848.30) to 1138.25 (593.87, 2009.27) pg/mL (P = 0.099). Plasma NGAL levels were positively associated with ALP in MHD patients; and downtrends were shown after PTX + AT in patients with severe SHPT. These findings suggest that NGAL is a participant in CKD-MBD under MHD condition.

Examination Subclinical Inflammatory Markers and Plasma Neutrophil Gelatinase-Associated Lipocalin in Obsessive-Compulsive Disorder

Background: Inflammation has a role in the etiopathogenesis of obsessive-compulsive disorder (OCD). Aims: We investigated the relationship of disease and disease severity with plasma neutrophil gelatinase-associated lipocalin (NGAL) level, and subclinical hemogram parameters in patients new diagnosed OCD. Methods: A total of 39,654 patients who presented to the ambulant psychiatry outpatient clinic, diagnosed a psychiatric diseases between January 2018 and October 2020 were evaluated DSM-5 criteria; 54 patients who were new diagnosis OCD included in the study. The hemogram was evaluated platelet (PLT) count, PLT–lymphocyte ratio (PLR), PLT- distribution witdth (PDW), neutrophil–lymphocyte ratio (NLR), C-reactive protein (CRP), and NGAL levels were analyzed in relation to an inflammatory condition. Results: A significant difference was found between disease severity and the PLT count, PDW, and NGAL values. PDW and NGAL values have relationship with disease severity by linear regression analysis. A significant difference was found the OCD with higher CRP, PDW, and a lower PLT value and showed a relationship between the PDW value by ROC analysis. Conclusion: This study was novel in reporting a significant relationship between the PDW level and the disease, and between the PDW and NGAL levels and disease severity in patients diagnosed with OCD. Keywords: CRP, NGAL, OCD, PDW, platelet count Special Issue of Health Sciences DOI: 10.7176/JSTR/7-08-04