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Background and Aim: Neutrophil gelatinase-associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. Methods: This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. Results: Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child-Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. Conclusion: Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

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Introduction: Diabetic kidney disease (DKD) is one of the major microvascular complications of type 1 diabetes mellitus (T1DM). Some studies suggest that changes of renal tubular components emerge before the glomerular lesions thus introducing the concept of diabetic tubulopathy with urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a potential marker of DKD. This concept was not confirmed in all studies. Materials and methods: In 198 T1DM patients with median age 15 years and diabetes duration over one year, an albumin/creatinine ratio (ACR) was determined and uNGAL measured in spot urine sample. Urine samples for ACR and uNGAL were also collected in the control group of 100 healthy children of similar age. Results: There was no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects (6.9 (2.8-20.1) ng/mL vs 7.9 (2.9-21.0) ng/mL, P = 0.969 and 6.8 (2.2-18.4) ng/mg vs 6.5 (1.9-13.4) ng/mg, P = 0.448, respectively) or between T1DM subjects with albuminuria A2 and albuminuria A1 (P = 0.573 and 0.595, respectively). Among T1DM patients 168 (85%) had normal uNGAL concentrations, while in 30 (15%) patients uNGAL was above the defined cut-off value of 30.9 ng/mL. There was no difference in BMI, HbA1c and diabetes duration between patients with elevated uNGAL compared to those with normal uNGAL. Conclusions: We found no significant difference in uNGAL concentration or uNGAL/creatinine between T1DM children and healthy subjects or between albuminuria A2 and albuminuria A1 T1DM subjects. Therefore, uNGAL should not be recommended as a single marker for detecting diabetic kidney disease in children and adolescents.

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Background: A serious problem in cirrhosis is acute renal injury. The study aimed to examine the urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a diagnostic and prognostic marker of acute kidney injury (AKI) in cirrhotic patients. Methods: A prospective study was carried out over a period of 1 year. A total of 490 patients suffering from cirrhosis who visited an indoor hospital were screened, and after the exclusion, a total of 90 subjects admitted to the medicine intensive care unit (MICU) fulfilling inclusion criteria were enrolled. Those having a history of renal diseases, on nephrotoxic drugs, in septic shock, peritonitis, UTI, and no urine output were excluded. On admission, for the estimation of uNGAL, urinary levels of sodium, creatinine, fresh urine samples were obtained, and blood samples were taken for serum creatinine estimation. Results: Out of 90 patients, 33.3% did not develop AKI, and 66.7% developed AKI. Urinary neutrophil gelatinase-associated lipocalin levels were six times higher in patients with acute tubular necrosis (259.08 ± 118.41 ng/mL) and three times higher in Hepatorenal syndrome (HRS)-AKI (124.97 ± 16.38) as compared with patients with normal kidney function (39.76 + 5.7). Those who died had a higher uNGAL (171.6 ng/mL) in comparison to those who survived (133.7 ng/mL). At a cutoff value of ≥114.9 (ng/mL), urinary NGAL represents a sensitivity of 86.92% and specificity of 100% to diagnose AKI and AUC 0.966 (95% CI: 0.919-0.990) in cirrhotic patients. Conclusion: Urinary NGAL is good for diagnosing AKI and is a marker to distinguish the types of AKI in liver cirrhosis. How to cite this article: Patel ML, Shyam R, Chaudhary A, Sachan R, Ali W. Urinary Neutrophil Gelatinase-associated Lipocalin as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Hospitalized Cirrhotic Patients: A Study from North Indian Population. Indian J Crit Care Med 2023;27(8):545-551.

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Background: Acute kidney injury (AKI) is common among critically ill children. The current definitions of AKI rely on serum creatinine and urine output, which may not be deranged until late in the course of the illness. There has been a lot of work in search of novel biomarkers to define and predict AKI, and urinary neutrophil gelatinase-associated lipocalin (NGAL) is a promising one. We planned to study the usefulness of urinary NGAL in predicting AKI. Patients and methods: Children in the age group of 1 month to 18 years admitted to the pediatric intensive care unit (PICU) from September 2016 to December 2017 were enrolled. Children with preexisting kidney disease, urinary tract infection (UTI), postsurgical patients, or children with expected duration of stay <48 hours were excluded. Data regarding demographics, clinical features, and laboratory parameters were collected. Urinary NGAL was sent within 6 hours of admission. Children were classified to have AKI based upon the Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (pRIFLE) criteria. Using receiver operating characteristic (ROC) curves, sensitivity, specificity, and area under the curve (AUC) for admission creatinine and urinary NGAL to predict AKI were deduced. Results: One hundred and thirty children were included. Out of 130 children, 59 (45.4%) developed AKI. Urinary NGAL at admission to the PICU >88.5 ng/mL had a sensitivity of 81.4% and specificity of 83.6% in detecting AKI while its AUC to detect AKI was 0.842 (95% confidence interval (CI) 0.765-0.918). Urinary NGAL predicted AKI in 17 (28.8%) of 59 patients at least 24 hours earlier than serum creatinine. Mortality rates in patients with and without AKI were 18.6 and 2.8%, respectively. Conclusion: Urinary NGAL has good sensitivity and specificity in detecting AKI and predicts AKI earlier than creatinine in a significant number of patients. How to cite this article: Kapalavai SK, Ramachandran B, Krupanandan R, Sadasivam K. Usefulness of Urinary Neutrophil Gelatinase-associated Lipocalin as a Predictor of Acute Kidney Injury in Critically Ill Children. Indian J Crit Care Med 2022;26(5):634-638.

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Aim: We explored the concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL) in healthy adults in the Jiangsu region in Eastern China and established a reference interval using latex-enhanced immunoturbidimetry to provide important guidelines for the interpretation and application of urinary NGAL in clinical practice. Methods: In total, 1970 eligible subjects from four regions were included in this study. The urinary NGAL levels were measured using an AU5800 automatic biochemical analyzer with its matched reagents. The urinary NGAL reference interval was established using the one-sided percentile method (95th percentile). Results: The urinary NGAL data were non-normally distributed. The urinary NGAL levels were not significantly different by sex or age. Therefore, the urinary NGAL reference interval in healthy adults in the Jiangsu region in Eastern China was <87.5 ng/ml (95th percentile of the upper limit). Conclusion: Urinary NGAL reference interval will play an important role in promoting the clinical value of urinary NGAL.

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In veterinary medicine, investigations relating the effects of hydroxyethyl starch (HES) on renal function report contrasting results. This study aimed to assess the changes in the selected biomarkers of kidney injury in dogs after the administration of HES 130/0.4 as a constant rate infusion (CRI) for 24 h. Ten adult client-owned dogs with hypoalbuminemia (albumin < 2 g/dL) and ongoing fluid losses were included. Enrolled dogs received intravenous fluid therapy with crystalloids and a CRI of HES 130/0.4 at a dose of 2 mL/kg/h for 24 h. Serum creatinine (sCr), fractional excretion (FE) of electrolytes, urinary protein to creatinine ratio (UPC), urinary albumin to creatinine ratio (UAC), SDS-page, and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were measured at the baseline before HES infusion, and after 24 h (T24) and 48 h (T48) from the baseline. No statistically significant difference was found between the baseline value vs. T24 and the baseline vs. T48 for sCr, UAC, UPC, FE of sodium, chloride and calcium, and uNGAL. A significant increase in FEK (p = 0.04) was noticed between the baseline and T48. In this study sample of hypoalbuminemic dogs, HES 130/0.4 at the dose and rate of infusion applied did not cause any significant changes in the investigated biomarkers of kidney injury.

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PURPOSE: We examined the clinical utility of perioperative monitoring of urinary liver-type fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and albumin, for prediction of acute kidney injury (AKI) and prediction of chronic renal dysfunction in patients undergoing open surgical repair (OSR) of an abdominal aortic aneurysm. PATIENTS AND METHODS: Urine and serum samples were obtained perioperatively from 64 such patients (n=64). Patients in whom OSR-related AKI (defined by the Kidney Disease Improving Global Outcomes criteria) occurred were identified. Renal function was evaluated 3 years after OSR in patients with OSR-related AKI. RESULTS: The urinary biomarkers examined increased to maximum levels by 2 hours after aortic cross-clamping (AXC), regardless of whether AKI occurred. Notably, the serum creatinine (Cr) levels increased significantly immediately after OSR in patients with AKI (n=19) (vs that in patients without AKI). In patients with AKI, the increased serum Cr elevation rate, the urinary L-FABP levels 2 hours after AXC and immediately after OSR, and a reduction in eGFR documented 3 years after OSR were significantly greater in patients who underwent suprarenal AXC (n=11) than in those who underwent infrarenal AXC (n=8). Furthermore, urinary L-FABP levels 2 hours after AXC correlated significantly with the reductions in eGFR 3 years after OSR in patients with AKI. CONCLUSION: Urinary L-FABP, NGAL and albumin concentrations 2 hours after AXC may be useful for early detection of OSR-related AKI. Furthermore, the increase in urinary L-FABP 2 hours after AXC may be predictive of chronic renal dysfunction in patients with OSR-related AKI.

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BACKGROUND: The most important finding that affects the prognosis in Familial Mediterranean Fever is renal amyloidosis. The aim of the present study was to analyze neutrophil gelatinase-associated lipocalin levels in the urine, and to investigate whether it may be used as an early marker for renal involvement. METHODS: Forty attack-free children followed by diagnosis of Familial Mediterranean Fever with age range of 5 and 18 years, and 38 healthy children with similar ages and genders were enrolled into the study. Hemogram, sedimentation, C-reactive protein, urine analysis, creatinine in the spot urine, microalbumin and urinary neutrophil gelatinase-associated lipocalin levels were analyzed and evaluated statistically in the patients and controls. RESULTS: There was not any statistically significant difference between the patient and control groups for age, gender, height and body weight. Although there was not any clinical sign of attack in the patient group, sedimentation, C-reactive protein and fibrinogen levels were significantly higher than the control group (p = 0.002, p = 0.023, and p = 0.006, respectively). Similarly, urinary neutrophil gelatinase-associated lipocalin level and urinary creatinine ratio were significantly higher in the patient group (p = 0.0001, p = 0.011, respectively). We found a positive correlation between uNGAL level and uNGAL/uCr ratio and number of attacks per year in FMF patients (r = 0.743, p = 0.001 and r = 0.516, p = 0.001; respectively). CONCLUSIONS: Detection of significantly higher levels of urinary neutrophil gelatinase-associated lipocalin level and urinary neutrophil gelatinase-associated lipocalin level to creatinine ratio were suggested as urinary neutrophil gelatinase-associated lipocalin level as a non-invasive marker for renal involvement better than microalbumin.

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BACKGROUND: The prevalence of acute kidney injury (AKI) in COVID-19 patients is high, with poor prognosis. Early identification of COVID-19 patients who are at risk for AKI and may develop critical illness and death is of great importance. OBJECTIVE: The aim of this study was to develop and validate a prognostic model of AKI and in-hospital death in patients with COVID-19, incorporating the new tubular injury biomarker urinary neutrophil gelatinase-associated lipocalin (u-NGAL) and artificial intelligence (AI)-based chest computed tomography (CT) analysis. METHODS: A single-center cohort of patients with COVID-19 from Wuhan Leishenshan Hospital were included in this study. Demographic characteristics, laboratory findings, and AI-assisted chest CT imaging variables identified on hospital admission were screened using least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a model for predicting the AKI risk. The accuracy of the AKI prediction model was measured using the concordance index (C-index), and the internal validity of the model was assessed by bootstrap resampling. A multivariate Cox regression model and Kaplan-Meier curves were analyzed for survival analysis in COVID-19 patients. RESULTS: One hundred seventy-four patients were included. The median (±SD) age of the patients was 63.59 ± 13.79 years, and 83 (47.7%) were men.u-NGAL, serum creatinine, serum uric acid, and CT ground-glass opacity (GGO) volume were independent predictors of AKI, and all were selected in the nomogram. The prediction model was validated by internal bootstrapping resampling, showing results similar to those obtained from the original samples (i.e., 0.958; 95% CI 0.9097-0.9864). The C-index for predicting AKI was 0.955 (95% CI 0.916-0.995). Multivariate Cox proportional hazards regression confirmed that a high u-NGAL level, an increased GGO volume, and lymphopenia are strong predictors of a poor prognosis and a high risk of in-hospital death. CONCLUSIONS: This model provides a useful individualized risk estimate of AKI in patients with COVID-19. Measurement of u-NGAL and AI-based chest CT quantification are worthy of application and may help clinicians to identify patients with a poor prognosis in COVID-19 at an early stage.

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OBJECTIVES: Kidney Disease: Improving Global Outcomes (KDIGO) guidelines include assessment of creatinine and urine output to identify acute kidney injury (AKI). Whether urine output is an accurate indicator of AKI after cardiac surgery, however, is unclear. The authors' goal was to examine whether cardiac surgery patients who fulfilled criteria for AKI by KDIGO urine output criteria also demonstrated kidney injury by elevated creatinine, other kidney biomarkers, or had worse clinical outcomes. DESIGN: Secondary analysis of prospectively collected data from a clinical trial, "6% Hydroxyethyl starch 130/0.4 in Cardiac Surgery (NCT02192502)." SETTING: Academic, quaternary care hospital. PARTICIPANTS: Patients undergoing elective aortic valve replacement INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: One hundred forty-one patients were classified into AKI stage by KDIGO urine output criteria within 24 hours after surgery. Kidney biomarkers (serum creatinine, urinary neutrophil gelatinase-associated lipocalin [NGAL], urinary interleukin-18 [IL-18]) and hospital and intensive care unit length of stay were analyzed across AKI stages. Urine output criteria classified four times as many patients with AKI than creatinine criteria (95 [67%] v 21 [15%]). Most patients meeting KDIGO urine output criteria for AKI postoperatively did not satisfy KDIGO creatinine criteria for AKI within one week (77 of 95 [81%]) or six-to-12 months (27 of 29 [93%]). Higher AKI stage assessed by urine output was not associated with higher NGAL, IL-18, or longer hospital or intensive care unit stays. CONCLUSIONS: Acute kidney injury classified by KDIGO urine output criteria was not associated with other biomarkers of kidney injury or worse patient outcomes. These data suggested that KDIGO urine output criteria after cardiac surgery may overclassify AKI stage; further research is needed.

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Abstract Background: The most important finding that affects the prognosis in Familial Mediterranean Fever is renal amyloidosis. The aim of the present study was to analyze neutrophil gelatinase-associated lipocalin levels in the urine, and to investigate whether it may be used as an early marker for renal involvement. Methods: Forty attack-free children followed by diagnosis of Familial Mediterranean Fever with age range of 5 and 18 years, and 38 healthy children with similar ages and genders were enrolled into the study. Hemogram, sedimentation, C-reactive protein, urine analysis, creatinine in the spot urine, microalbumin and urinary neutrophil gelatinase-associated lipocalin levels were analyzed and evaluated statistically in the patients and controls. Results: There was not any statistically significant difference between the patient and control groups for age, gender, height and body weight. Although there was not any clinical sign of attack in the patient group, sedimentation, C-reactive protein and fibrinogen levels were significantly higher than the control group (p = 0.002, p = 0.023, and p = 0.006, respectively). Similarly, urinary neutrophil gelatinase-associated lipocalin level and urinary creatinine ratio were significantly higher in the patient group (p = 0.0001, p = 0.011, respectively). We found a positive correlation between uNGAL level and uNGAL/uCr ratio and number of attacks per year in FMF patients (r =0.743, p =0.001 and r =0.516, p =0.001; respectively). Conclusions: Detection of significantly higher levels of urinary neutrophil gelatinase-associated lipocalin level and urinary neutrophil gelatinase-associated lipocalin level to creatinine ratio were suggested as urinary neutrophil gelatinase-associated lipocalin level as a non-invasive marker for renal involvement better than microalbumin.

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Elevated urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts acute kidney injury (AKI) in children following cardiopulmonary bypass (CPB) during cardiac surgery, but little is known about uNGAL's predictive ability in neonates in this setting. We sought to determine the relationship between AKI and post-CPB uNGAL in neonates in the first 72 post-operative hours. METHODS: Urine samples for uNGAL analysis were collected at preoperative baseline and serially post-operatively from 76 neonates undergoing CPB. Mixed-effects regression models and logistic models assessed associations between uNGAL and AKI (controlling for sex, gestational age, CPB time, surgical complexity, and age at surgery). Receiver-operator curves were applied to define optimal uNGAL cut-off values for AKI diagnosis. RESULTS: Between 0 and 4 h post-operatively, uNGAL values did not differ between neonates with and without AKI. After 4 h until 16 h post-operatively, significant time-wise separation occurred between uNGAL values of neonates with AKI and those without AKI. Odds ratios at each time point significantly exceeded unity, peaking at 10 h post-operatively (3.48 (1.58, 8.71)). Between 4 and 16 h post-operatively, uNGAL discriminated AKI from no-AKI, with a sensitivity of 0.63 (0.49, 0.75) and a specificity of 0.68 (0.62, 0.74) at a cut-off value of 100 ng/mL. CONCLUSION: After 4 h until 16 h post-operatively, elevated uNGAL is associated with AKI in neonates receiving CPB during cardiac surgery; however, this relationship is more complex than in older children.

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Background/aim: Neutrophil gelatinase-associated lipocalin (NGAL) is used previously to estimate the etiology, severity, and clinical outcomes of acute kidney injury (AKI). However, the role of urinary NGAL (uNGAL) in the postrenal setting is not clear. In our study, we aimed to discover the cut-off value of uNGAL that can be used in the differential diagnosis of underlying AKI etiologies. Materials and methods: In this prospective cross-sectional study, we examined 82 subjects in four groups: patients that had (1) postrenal AKI; (2) AKI other than postrenal etiologies; (3) stable chronic kidney disease; and (4) healthy subjects. A renal function assessment was carried out by measuring serum creatinine (sCr) and uNGAL at the time of diagnosis [0th min (T0)]. We followed the study group for three months. Results: At the time of diagnosis, sCr (T0) was highest in the postrenal AKI and AKI groups in contrast to stable chronic kidney disease patients and healthy subjects (P < 0.001), as expected. T0 median uNGAL was highest in the postrenal group (P < 0.001). Area under curve (AUC) of uNGAL to estimate postrenal AKI presence was 0.957 (95% CI, 0.897­1.000; P < 0.001). The cut-off point of uNGAL was 42.625 ng/mL for this estimation. Conclusion: Patients with AKI must be classified according to the underlying etiologies as soon as possible. uNGAL may be useful to estimate the etiologies, and whether the problem is acute or chronic in the course. In postrenal kidney problems, to plan the urgency of the urologic procedures, it is crucial.

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BACKGROUND: Most effective method for reducing mortality from hepatocellular carcinoma (HCC) is early diagnosis. Despite its lack of adequate sensitivity, ultrasound is considered fundamental for HCC screening. AIM: to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) as non-invasive marker for HCC diagnosis in Egyptian patients. METHODS: One hundred and twenty patients were divided into three groups (40 patients each): patients with chronic viral hepatitis (HCV or HBV), cirrhotic patients and HCC patients and 40 healthy age and gender matched subjects were enrolled as control group. After clinical assessments, urinary NGAL was measured by enzyme-linked immunosorbent assay. RESULTS: Our results revealed that median level of urinary NGAL was 290, 834, 1090 and 1925 pg/ml in control, chronic hepatitis, cirrhotic and HCC groups respectively among studied groups (p<0.001). Receiver operating characteristics (ROC) analysis showed that urinary NGAL cutoff value of 1255 ng/ml could discriminate between HCC and cirrhosis. The area under curve (AUC) was 0.95 with 90% sensitivity, 87.5% specificity (p-value <0.001). In HCC group, urine NGAL level didn`t show significant correlation with Child Pugh score, MELD score or Barcelona Clinic Liver Cancer (BCLC) stage. CONCLUSION: Urinary NGAL could be a simple, non-invasive test for diagnosis of HCC in chronic liver disease patients.
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BACKGROUND: CHDs can be complicated by renal injury which worsens morbidity and mortality. Urinary neutrophil gelatinase-associated lipocalin, a sensitive and specific biomarker of renal tubular injury, has not been studied in children with uncorrected CHDs. This study evaluated renal injury in children with uncorrected CHDs using this biomarker. METHODS: The patients were children with uncorrected CHDs with significant shunt confirmed on echocardiogram with normal renal ultrasound scan, in the paediatric cardiology clinic of a tertiary hospital. The controls were age-matched healthy children recruited from general practice clinics. Information on bio-data and socio-demographics were collected and urine was obtained for measurement of urinary neutrophil gelatinase-associated lipocalin levels. RESULTS: A total of 65 children with uncorrected CHDs aged 2 to 204 months were recruited. Thirty-one (47.7%) were males while 36 (55.4%) had acyanotic CHDs. The median urinary neutrophil gelatinase-associated lipocalin level of patients of 26.10 ng/ml was significantly higher than controls of 16.90 ng/ml (U = 1624.50, p = 0.023). The median urinary neutrophil gelatinase-associated lipocalin level of patients with cyanotic and acyanotic CHDs were 30.2 ng/ml and 22.60 ng/ml respectively; (Mann-Whitney U = 368.50, p = 0.116). The prevalence of renal injury using 95th percentile cut-off value of urinary neutrophil gelatinase-associated lipocalin was 16.9%. Median age of patients with renalinjury was 16 (4-44) months. CONCLUSIONS: Children with uncorrected CHDs have renal injury detected as early as infancy. The use of urinary neutrophil gelatinase-associated lipocalin in early detection of renal injury in these children may enhance early intervention and resultant prevention of morbidity and reduction in mortality.

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OBJECTIVE: Chronic kidney disease (CKD) related to diabetes has become more common than glomerulonephritis in recent years. Given the inefficient and difficult identification of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) as well as a result of emerging evidence supporting a role for tubular involvement in DKD, we aimed to investigate the utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in the differential diagnosis and predictive value of DKD from NDKD. METHODS: Data for 100 type 2 diabetic patients with CKD at our center from June 2016 to August 2019 were reviewed. All the patients were categorized into 2 groups by the renal biopsy results: DKD and NDKD. Urinary NGAL levels were normalized by urinary creatinine and calculated as uNGAL/creatinine ratios (uNCR). The independent factors of the occurrence of DKD and the diagnostic implications of uNCR were explored by logistic regression and receiver-operating characteristic (ROC) curve analysis. In addition, we analyzed the relationship between uNCR and proteinuria in patients with DKD by Pearson test and linear regression. Kaplan-Meier survival analysis was performed to assess the prospective association of uNCR with the renal outcome. RESULTS: Significantly higher levels of uNCR were observed in patients with DKD when compared to those with NDKD (28.65 ng/mg vs 27.47 ng/mg, p< .001). uNCR was identified as an independent risk factor for the occurrence of DKD in diabetic patients with CKD (odds ratio [OR] = 1.020; 95%CI = [1.001-1.399], p = .042). The optimal cutoff value of uNCR for predicting DKD was 60.685 ng/mg with high specificity (90.5%) but relatively low sensitivity (55.7%). In Pearson test, uNCR was positively correlated with proteinuria, serum creatine, blood urea nitrogen, duration of diabetes, interstitial inflammation score and global sclerosis, whereas it was inversely correlated with eGFR, hemoglobin, serum albumin and 25-hydroxy vitamin D. Furthermore, in a fully adjusted model including eGFR, serum albumin and total cholesterol, the group with uNCR>60.685 ng/mg was associated with 7.595 times higher likelihood of nephrotic-range proteinuria compared to the group with uNCR≤60.685 ng/mg. In the Kaplan-Meier survival analysis, the event-free survival probability in patients with uNCR>60.685 ng/mg was significantly lower than those with uNCR≤60.685 ng/mg (p = .048). CONCLUSIONS: uNCR might serve as a potential tool for identifying cases in which there was a high clinical suspicion of DKD and that in whom confirmatory biopsy could be considered, and the best predictive cutoff value of normalized uNCR for DKD diagnosis was 60.685 ng/mg. Type 2 diabetic patients with increased level of uNCR had higher risk to nephrotic-range proteinuria and worse renal outcome.

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BACKGROUND: Acute kidney injury (AKI) is a common complication in critical care patients. The presence of AKI is a marker for poor outcomes such as longer hospitalization durations, more hospital readmissions, and especially, higher mortality rates. Sepsis is one of the major causes of AKI within the intensive care unit (ICU) population. Sepsis-related AKI occurs in approximately 20% of patients, reaching more than 50% in patients with septic shock. The diagnosis of AKI depends on urine output and/or serum creatinine measurements. Unfortunately, serum creatinine is a late and unreliable (insensitive and nonspecific) indicator of AKI. However, biomarkers of renal damage have great potential in facilitating early diagnosis of AKI. Several biomarkers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL), have been used in the early detection of AKI. OBJECTIVES: The aim of this study was to evaluate uNGAL for the diagnosis and prognosis of AKI in critical ill patients with infections. DESIGN: Original study (Cohort Prospective Observational). SETTING: Study in 2 ICUs of different Brazilian hospitals, in the city of Curitiba: Hospital de Clínicas da Universidade Federal do Paraná and Hospital da Polícia Militar do Paraná, from November 12, 2016 to May 15, 2018. PARTICIPANTS: Critically ill patients with infections, sepsis, or septic shock were selected. The inclusion criteria were patients older than 18 years with infection. They were followed up for 30 days in the analysis of outcomes. We requested that consent forms be signed by all eligible patients or their caregivers. MEASUREMENTS: The urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels of the patients were measured on 4 consecutive days and was assayed using a chemiluminescent microparticle immunoassay system. The screening time occurred within 72 hours of admission to the ICU. The first urine sample was collected within the first 24 hours of the screening hours. Mortality and AKI were assessed during first 30 days. METHODS: clinical and laboratory data, including daily uNGAL levels, were assessed. The AKI stage using the KDIGO criteria was evaluated. Sensitivity, specificity, and the area under the curve-receiver operating characteristic (AUC-ROC) values were calculated to determine the optimal uNGAL level for predicting AKI. RESULTS: We had 38 patients who completed the study during the screening period. The incidence of AKI was 76.3%. The hospitalization period was longer in the group that developed AKI, with 21 days of median (interquartile range [IQR]: 13.5-25); non-AKI group had a median of 13 days (IQR 7-18; P = .019). We found a direct relationship between uNGAL levels and the progression to AKI. Increased values of the biomarker were associated with the worsening of AKI (P < .05). The cutoff levels of uNGAL that identified patients who would progress to AKI were the following: (d1) >116 ng/mL, (d2) >100 ng/mL, and (d3) 284 ng/mL. The value of the fourth and last measurement was not predictive of patients who would progress to AKI. The median urinary uNGAL was also associated with mortality on Days 1, 3, and 4: d1, P = .039; d3, P = .005; d4, P = .005. The performance of uNGAL in detecting AKI patients (AUC-ROC = 0.881). There were no risk factors other than AKI that could be correlated with increased uNGAL levels on Day 1. LIMITATIONS: The study was carried out in 2 centers, having used only 1 biomarker, and our small number of patients were limitations. CONCLUSION: the uNGAL had an association in its values with the diagnosis and prognosis of patients with severe infections and AKI. We suggest that studies with a greater number of patients could better establish the cutoff values of uNGAL and/or serum NGAL in the identification of infected patients who are at a high risk of developing AKI.

CONTEXTE`: L'insuffisance rénale aiguë (IRA) est une complication fréquente chez les patients des unités de soins intensifs (USI). L'IRA est un marqueur d'issues défavorables pour ces patients, notamment d'hospitalisations plus longues, de réadmissions plus fréquentes et surtout, de taux de mortalité plus élevés. Le sepsis est une des principales causes d'IRA chez les patients soignés aux USI; cette infection liée à l'IRA survient chez environ 20 % des patients et peut toucher plus de 50 % des patients en choc septique. Le diagnostic de l'IRA repose sur la mesure de la diurèse ou du taux de créatinine sérique; cette dernière mesure s'avérant toutefois un indicateur tardif et peu fiable (non spécifique et peu sensible). Les biomarqueurs d'une lésion rénale pourraient potentiellement faciliter un diagnostic précoce de la maladie. Plusieurs, dont la NGAL urinaire ou uNGAL (urinary neutrophil gelatinase-associated lipocalin) ont déjà été utilisés dans ce contexte. OBJECTIFS: Évaluer le potentiel de la uNGAL pour le diagnostic et le pronostic de l'IRA chez les patients gravement malades souffrant d'infections. TYPE D'ÉTUDE: Étude initiale (étude de cohorte prospective et observationnelle). CADRE: L'étude s'est tenue entre le 12 novembre 2016 et le 15 mai 2018 dans les USI de deux hôpitaux de Curitiba au Brésil (Hospital de Clínicas da Universidade Federal do Paraná et Hospital da Polícia Militar do Paraná). SUJETS: Les patients adultes, gravement malades et atteints d'une infection, d'un sepsis ou d'un choc septique ont été retenus. Le consentement écrit de tous les patients admissibles et de leurs représentants était exigé. Les sujets ont été suivis pendant 30 jours pour l'analyse des résultats. MESURES: Les taux d'uNGAL ont été mesurés pendant quatre jours consécutifs et analysés par immunodosage microparticulaire par chimiluminescence. Le dépistage a eu lieu dans les 72 heures suivant l'admission aux USI et le premier échantillon d'urine a été prélevé dans les 24 premières heures de la période de dépistage. L'IRA et la mortalité ont été évaluées pendant les 30 premiers jours. MÉTHODOLOGIE: L'analyse porte sur les données cliniques et de laboratoire, y compris les taux quotidiens d'uNGAL. Le stade de l'IRA a été établi selon les critères KDIGO. La sensibilité, la spécificité et les valeurs de surface sous la courbe ROC (SSC-ROC) ont servi à calculer le taux optimal d'uNGAL prédictif de l'IRA. RÉSULTATS: L'incidence de l'IRA s'établissait à 76,3 % parmi les 38 patients ayant complété le dépistage. Les patients souffrant d'IRA étaient hospitalisés plus longtemps que les autres (durée médiane: 21 jours [ÉIQ: 13,5-25] contre 13 jours [ÉIQ: 7-18] pour les autres patients; p=0,019). Un lien direct entre le taux d'uNGAL et une progression vers l'IRA a été observé, et l'augmentation de ces valeurs a été associée à une aggravation de l'IRA (p<0,05). Les valeurs seuil d'uNGAL permettant de diagnostiquer une évolution vers l'IRA étaient les suivantes: (j1) > 116 ng/mL; (j2) > 100 ng/mL et (j3) 284 ng/mL. La valeur de la 4e et dernière mesure n'a pas permis de prédire une évolution vers l'IRA. Les taux médians d'uNGAL ont également été associés à la mortalité aux jours 1,3 et 4; avec des valeurs de p s'établissant à 0,039 (j1), 0,005 (j3) et 0,005 (j4). La performance du taux d'uNGAL pour détecter l'IRA (SSC-ROC) était de 0,881. Aucun facteur de risque autre que l'IRA n'a pu être corrélé avec une augmentation du taux d'uNGAL au jour 1. LIMITES: L'étude ne s'est tenue que dans deux centres, sur un échantillon restreint de patients, et ne portait que sur un seul biomarqueur. CONCLUSION: Le taux d'uNGAL a montré une association avec le diagnostic et le pronostic des patients souffrant d'infections graves et d'IRA. Nous pensons que des études sur un plus grand nombre de patients pourraient préciser les valeurs seuil d'uNGAL ou de NGAL sérique pour le dépistage des patients infectés qui présentent un risque élevé de développer une IRA.

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OBJECTIVES: To study the effects of running with/without the use of pain killers on urinary neutrophil gelatinase-associated lipocalin (uNGAL) and other parameters of kidney function in recreational runners. METHODS: Participants of the 10- and 21.1-km Weir Venloop race were enrolled and their urine samples collected before and after the run. Urine dipstick and other conventional tests used to assess kidney function were performed. The presence of ibuprofen, diclofenac, naproxen, and/or paracetamol was assessed by LC-MS/MS. uNGAL was measured with a two-step chemiluminescent immunoassay. RESULTS: NSAIDs/analgesics were detected in urine of 5 (14.4%) 10-km runners and 13 (28.9%) 21.1-km runners. Only half-marathon participants showed significant increases in uNGAL (pre: 11.7 [7.1-34.3] ng/mL; post: 33.4 [17.4-50.4] ng/mL; P = .0038). There was a significant effect of NSAID/analgesic use on uNGAL increase (F2, 76  = 4.210, P = .004). Post hoc tests revealed that uNGAL increased significantly in runners who tested positive for ibuprofen/naproxen compared to runners who did not use any medications (P = .045) or those who tested positive for paracetamol (P = .033). Running distance had a significant influence on the increase in uNGAL (F1, 53  = 4.741, P < .05), specific gravity (F1, 60  = 9.231, P < .01), urinary creatinine (F1, 61  = 10.574, P < .01), albumin (F1, 59  = 4.888, P < .05), and development of hematuria (χ2 (4) = 18.44, P = .001). CONCLUSIONS: Running distance and use of ibuprofen/naproxen were identified as risk factors for uNGAL increase in recreational runners.

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Whether third-generation hydroxyethyl starch solutions provoke kidney injury or haemostatic abnormalities in patients having cardiac surgery remains unclear. We tested the hypotheses that intra-operative administration of a third-generation starch does not worsen postoperative kidney function or haemostasis in cardiac surgical patients compared with human albumin 5%. This triple-blind, non-inferiority, clinical trial randomly allocated patients aged 40-85 who underwent elective aortic valve replacement, with or without coronary artery bypass grafting, to plasma volume replacement with 6% starch 130/0.4 vs. 5% human albumin. Our primary outcome was postoperative urinary neutrophil gelatinase-associated lipocalin concentrations, a sensitive and early marker of postoperative kidney injury. Secondarily, we evaluated urinary interleukin-18; acute kidney injury using creatinine RIFLE criteria, coagulation measures, platelet count and function. Non-inferiority (delta 15%) was assessed with correction for multiple comparisons. We enrolled 141 patients (69 starch, 72 albumin) as planned. Results of the primary analysis demonstrated that postoperative urine neutrophil gelatinase-associated lipocalin (median (IQR [range])) was slightly lower with hydroxyethyl starch (5 (1-68 [0-996]) ng.ml-1 ) vs. albumin (5 (2-74 [0-1604]) ng.ml-1 ), although not non-inferior [ratio of geometric means (95%CI) 0.91 (0.57, 1.44); p = 0.15] due to higher than expected variability. Urine interleukin-18 concentrations were reduced, but interleukin-18 and kidney injury were again not non-inferior. Of 11 individual coagulation measures, platelet count and function, nine were non-inferior to albumin. Two remaining measures, thromboelastographic R value and arachidonic acid-induced platelet aggregation, were clinically similar but with wide confidence intervals. Starch administration during cardiac surgery produced similar observed effects on postoperative kidney function, coagulation, platelet count and platelet function compared with albumin, though greater than expected variability and wide confidence intervals precluded the conclusion of non-inferiority. Long-term mortality and kidney function appeared similar between starch and albumin.

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OBJECTIVES: To investigate the changes of serum cystatin C (Cys-C), beta 2-microglobulin (ß2-MG), urinary neutrophil gelatinase-associated lipocalin (NGAL), and alpha 1-microglobulin (α1-MG) in asphyxiated neonates, and to evaluate the value of combined detection of multiple biomarkers in the early diagnosis of acute kidney injury (AKI) in asphyxiated neonates. METHODS: A total of 110 full-term asphyxiated and 30 healthy neonates were included. The asphyxia neonates were divided into AKI and non-AKI groups. Serum Cys-C, ß2-MG, urine NGAL, and α1-MG were measured 24 h after birth. The diagnostic value of the biomarkers was determined using receiver operating characteristic (ROC) curves. RESULTS: There was no significant difference in serum creatinine and blood urea nitrogen among the control group, moderate asphyxia group, and severe asphyxia group at 24 h after birth. Significant differences were noticed in terms of serum Cys-C, ß2-MG, urinary NGAL, and α1-MG among the 3 groups. Moreover, with the aggravation of asphyxia, the above indicators gradually increased. There were significant differences in the 4 indicators between the AKI and non-AKI groups (p < 0.05). The area under the ROC curve of the above indicators was 0.670, 0.689, 0.865, and 0.617, respectively (p < 0.05). The sensitivity and specificity of the combined diagnosis of asphyxia neonatorum AKI with the 4 indicators were 0.974 and 0.506, respectively. CONCLUSIONS: Serum Cys-C, ß2-MG, urine NGAL, and α1-MG are early specific indicators for the diagnosis of renal injury after neonatal asphyxia. Combined detection of these parameters could aid clinical evaluation of renal injury in asphyxiated neonates.

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