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.

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.

Usefulness of Urinary Neutrophil Gelatinase-associated Lipocalin as a Predictor of Acute Kidney Injury in Critically Ill Children.

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.

Prognostic Utility of KDIGO Urine Output Criteria After Cardiac Surgery.

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.

Non-steroidal anti-inflammatory drugs increase urinary neutrophil gelatinase-associated lipocalin in recreational runners.

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.

Clinical and subclinical acute kidney injury in multidrug-resistant septic patients treated with colistimethate sodium: Incidence and clinical outcomes.

AIM: Colistimethate sodium (CMS) has been postulated as the principal cause of high incidence of clinical acute kidney injury (AKI) in multidrug-resistance (MDR) septic patients with normal baseline serum creatinine (sCr) who were treated with CMS. This prospective observational study was conducted to examine the incidence and clinical outcomes of clinical and subclinical AKI in MDR septic patients receiving CMS. METHODS: Forty-two MDR septic patients with normal sCr who required CMS were included. Clinical AKI was diagnosed by increased sCr levels according to the KDIGO2012 criteria while subclinical AKI was identified by elevated levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL > 150 ng/mL) or urinary liver-type fatty-acid-binding protein (uL-FABP > 10.5 ng/mL). RESULTS: Clinical AKI was noted in 47.6% of patients on day 5 and 38.1% on day 7 after initiating CMS. By using uL-FABP, subclinical AKI was observed in 45.2% and 54.8% on day 5 and 7, respectively. At baseline prior to CMS treatment, subclinical AKI was already present in 90%. The baseline uL-FABP was superior to the baseline uNGAL in early prediction of clinical AKI on day 5. The subclinical AKI patients had comparable worse outcomes as clinical AKI patients. CONCLUSION: The incidence of subclinical AKI in MDR septic patients before CMS treatment was extremely high. The baseline uL-FABP provided the best predictive capacity of clinical AKI. The causes of clinical AKI might include the persistence of sepsis process, subclinical AKI and CMS nephrotoxicity. Proper management of subclinical AKI patients before CMS initiation should be concerned to prevent further renal damage and improve patient and renal outcomes.

Effect of 6% hydroxyethyl starch 130/0.4 on kidney and haemostatic function in cardiac surgical patients: a randomised controlled trial.

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.

Evaluation of renal injury in children with uncorrected CHDs with significant shunt using urinary neutrophil gelatinase-associated lipocalin.

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.

Evaluation of Novel Biomarkers for Early Diagnosis of Acute Kidney Injury in Asphyxiated Full-Term Newborns: A Case-Control Study.

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.

Urinay neutrophil gelatinase-associated lipocalin as a biomarker in different renal problems

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.

Role of Urinary Neutrophil Gelatinase-associated Lipocalin as a Biomarker of Acute Kidney Injury in Patients with Circulatory Shock.

BACKGROUND: The early prediction of acute kidney injury (AKI) by the current clinical and laboratory methods remains inadequate. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising noninvasive biomarker of kidney injury in shock. The aim of this study was to assess the ability of urinary NGAL (uNGAL) to predict AKI in adult Intensive Care Unit (ICU) patients. MATERIALS AND METHODS: We prospectively studied 70 patients with circulatory shock admitted to the ICU over a period of 1 year. uNGAL was analyzed at ICU admission and after 24 h. Risk, injury, failure, loss, and end-stage kidney criteria were calculated at admission and for consecutive 4 days. The primary outcome was AKI defined as an increase in creatinine of at least 50% from baseline or a reduction in urine output to <0.5 ml/kg/h for 6 h. RESULTS: uNGAL was a good diagnostic marker for AKI development; at day 1, the cutoff value 48.54 ng/mL had a sensitivity and specificity of 79.49 and 73.14, respectively, and the area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.75-0.87) for predicting AKI. At day 2, the cutoff value 190.92 ng/mL had a sensitivity and specificity of 90.0 and 64.66, respectively, and the AUC of 0.76 (95% CI, 0.70-0.88) for predicting AKI. CONCLUSION: uNGAL could be a good early predictor biomarker of AKI following circulatory shock.

Renal function and novel urinary biomarkers in infants with neonatal encephalopathy.

AIM: Perinatal asphyxia is associated with multi-organ injury including acute kidney injury (AKI). New urinary biomarkers may detect more subtle renal injury. METHODS: Urinary biomarkers (albumin, beta-2 microglobulin, cystatin-C, epidermal growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin) were serially measured from days 1 to 7 in term infants with perinatal asphyxia and controls and compared to 'Kidney Disease Improving Global Outcome' scoring of renal injury and to encephalopathy grade. RESULTS: A total of 255 urine samples were taken from infants exposed to perinatal asphyxia (n = 82) and term controls (n = 10). Thirty-nine infants underwent therapeutic hypothermia, four died and 30 infants had acute kidney injury. Infants with acute kidney injury had significantly higher levels of urinary albumin (day 2), cystatin-C (days 1, 2, 3 and 7), neutrophil gelatinase-associated lipocalin (days 2, 3 and 7) and osteopontin (days 2, 3 and 7) and lower epidermal growth factor and uromodulin (day 1) compared to those without AKI. Day 2 cystatin-C predicted AKI with an area under receiver operating characteristic curve of 0.89, p < 0.001, cut-off 9.8 × 104  pg/mL. NE grade II/III infants had significantly elevated levels of urinary cystatin-C, neutrophil gelatinase-associated lipocalin and decreased EGF compared to grade 0/I infants. CONCLUSION: Asphyxiated infants who develop acute kidney injury have significantly altered urinary biomarkers postnatally. Validation of neonatal AKI urinary biomarkers in a large prospective study is required. Long-term follow-up of infants post-asphyxial insult for chronic renal injury is advised.

Urinary neutrophil gelatinase-associated lipocalin for diagnosis and estimating activity in lupus nephritis: a meta-analysis.

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is relatively specific in lupus nephritis (LN) patients. However, its diagnostic value has not been evaluated. The aim of this review was to determine the value of uNGAL for diagnosis and estimating activity in LN. A comprehensive search was performed on PubMed, EMBASE, Web of Knowledge, Cochrane electronic databases through December 2014. Meta-analysis of sensitivity and specificity was performed with a random-effects model. Additionally, summary receiver operating characteristic (SROC) curves and area under the curve (AUC) values were calculated. Fourteen studies were selected for this review. With respect to diagnosing LN, the pooled sensitivity and specificity were 73.6% (95% confidence interval (CI), 61.9-83.3) and 78.1% (95% CI, 69.0-85.6), respectively. The SROC-AUC value was 0.8632. Regarding estimating LN activity, the pooled sensitivity and specificity were 66.2% (95% CI, 60.4-71.7) and 62.1% (95% CI, 57.9-66.3), respectively. The SROC-AUC value was 0.7583. In predicting renal flares, the pooled sensitivity and specificity were 77.5% (95% CI, 68.1-85.1) and 65.3% (95% CI, 60.0-70.3), respectively. The SROC-AUC value was 0.7756. In conclusion, this meta-analysis indicates that uNGAL has relatively fair sensitivity and specificity in diagnosing LN, estimating LN activity and predicting renal flares, suggesting that uNGAL is a potential biomarker in diagnosing LN and monitoring LN activity.

Urinary NGAL in gastrointestinal diseases can be used as an indicator of early infection in addition to acute kidney injury marker.

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.

Is the urinary neutrophil gelatinase-associated lipocalin concentration in children and adolescents with type 1 diabetes mellitus different from that in healthy children?

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.

Reference interval for urinary neutrophil gelatinase-associated lipocalin in healthy adults in Jiangsu region in Eastern China: a multicenter study.

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.

Using urinary neutrophile gelatinase-associated lipocalin for prognosticate renal dysfunction in children with familial Mediterranean fever the study design: a pilot study.

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.

Stage 1-Biomarkers of Kidney Injury in Dogs Undergoing Constant Rate Infusion of Hydroxyethyl Starch 130/0.4.

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.

Incorporation of Urinary Neutrophil Gelatinase-Associated Lipocalin and Computed Tomography Quantification to Predict Acute Kidney Injury and In-Hospital Death in COVID-19 Patients.

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.

Clinical Utility of Urinary Biomarkers for Prediction of Acute Kidney Injury and Chronic Renal Dysfunction After Open Abdominal Aortic Aneurysm Repair.

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.

Urine Neutrophil Gelatinase-Associated Lipocalin a Possible Diagnostic Marker for Egyptian Hepatocellular Carcinoma Patients.

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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