Urinary Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury that has been adapted to a urine dipstick test. However, there is limited data on its use in low-and-middle-income countries where diagnosis of acute kidney injury remains a challenge. To study this, we prospectively enrolled 250 children with sickle cell anemia aged two to 18 years encompassing 185 children hospitalized with a vaso-occlusive pain crisis and a reference group of 65 children attending the sickle cell clinic for routine care follow up. Kidney injury was defined using serial creatinine measures and a modified-Kidney Disease Improving Global Outcome definition for sickle cell anemia. Urine NGAL was measured using the NGAL dipstick and a laboratory reference. The mean age of children enrolled was 8.9 years and 42.8% were female. Among hospitalized children, 36.2% had kidney injury and 3.2% died. Measured urine NGAL levels by the dipstick were strongly correlated with the standard enzyme-linked immunosorbent assay for urine NGAL (hospitalized children, 0.71; routine care reference, 0.88). NGAL levels were elevated in kidney injury and significantly increased across injury stages. Hospitalized children with a high-risk dipstick test (300ng/mL and more) had a 2.47-fold relative risk of kidney injury (95% confidence interval 1.68 to 3.61) and 7.28 increased risk of death (95% confidence interval 1.10 to 26.81) adjusting for age and sex. Thus, urine NGAL levels were found to be significantly elevated in children with sickle cell anemia and acute kidney injury and may predict mortality.

Evaluation of Crocin Effect on Contrast-Induced Nephropathy Following Coronary Angiography or Angioplasty: A Randomized Controlled Trial.

Contrast-induced nephropathy (CIN) is the third cause of hospital-acquired acute kidney injury. The CIN prophylactic strategies adopted to date, although not highly efficient, are mostly based on antioxidant activity and hydration therapy. This study was designed and conducted to evaluate crocin’s efficacy in the prevention of CIN in chronic kidney disease (CKD) patients undergoing coronary angiography/angioplasty. In this randomized clinical trial, a total of 110 eligible CKD stage 3 patients requiring contrast agent administration for coronary angiography/angioplasty were enrolled and randomly assigned to either crocin (n = 57) or control (n = 53) group. The patients in both groups received standard hydration therapy; nevertheless, in the crocin group, the patients were also orally administered three consecutive oral doses of 30 mg crocin tablets 1 day before up to 1 day after contrast media (CM) exposure. The primary endpoint was CIN incidence defined as an increase in serum creatinine (SrCr) level by ≥ 0.3 mg/dL or any change in urinary neutrophil gelatinase-associated lipocalin (NGAL) from the baseline within 48 hours of CM exposure. During 4 months, 130 patients were recruited. The mean age of the patients was 65.62 ± 9.05 years, and the majority of them were male (64.54%). The SrCr in the crocin group did not significantly increase within 48 hours of angiography/angioplasty. The changes in the urinary NGAL level were not significant in both groups. The CIN incidence was significantly lower in the crocin group than in the control group (1.75% and 13.2%; P = 0.028). Crocin administration plays an important nephron-protective role in the prevention of CIN.

The Use of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Diagnostic and Prognostic Biomarker in Urinary Tract Obstruction: a Systematic Review.

The early recognition of urinary tract obstruction (UTO) is vital in order to prevent mortality and morbidity associated with an acute kidney injury (AKI) and progression to irreversible kidney damage. Urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) have been recognised as an accurate tool in the timely diagnosis of AKI, but its role in the detection, prognosis and subsequent monitoring of a variety of obstructive uropathies has not yet been explored. We performed a systematic review of literature in accordance with Cochrane methodology from inception to August 2021. Eleven studies were included in which urine and serum NGAL were measured (616 patients) presenting with multiple UTO aetiologies. Four investigated kidney stone disease (KSD) exclusively, whilst other studies identified other causes of UTO including pelviureteric junction obstruction (PUJO), retroperitoneal fibrosis (RPF) and ureteric strictures. Six studies monitored NGAL levels after surgical intervention to relieve the obstruction. Nine studies demonstrated a significant increase in both urine and serum NGAL levels in UTO, often in a more sensitive and timely manner than serum creatinine. Subclinical unilateral UTO could be recognised by urinary NGAL levels even in the absence of changes in serum creatinine. Following surgical intervention, a reduction in urinary and serum NGAL was seen in all but two studies. NGAL levels decreased acutely by 14% in 2h and showed a long-term reduction of 78% in 6months. Readily available but not yet widely accepted, NGAL has the potential to be a less invasive, low-cost diagnostic test for urinary tract obstructions as a whole. Not only can it be used as a marker of treatment success but also to monitor for obstruction recurrence or progression. Further research is required to acknowledge urinary biomarkers such as NGAL as a potential replacement to standard renal function monitoring tests in the context of obstructive uropathy.

NGAL and KIM-1 – early urinary biomarkers of nephrotoxicity mediated by cisplatin: Observational study

Background. Cisplatin is widely used in modern oncological practice. Despite high efficacy treatment with cisplatin is conjugated with high risk of nephrotoxicity. Approximately one third of patients develop renal disfunction after first injection of cisplatin. In clinical practice serum creatinine elevation is used as a marker of renal damage, which is observed after failure of 50% of kidney function. That is why the finding of early biomarker of nephrotoxicity is still an issue. NGAL and KIM-1 are markers of renal damage, the predictive value of which has been described in cardiac surgery and resuscitation practice: an increase in the concentration of these markers in urine precedes the development of renal damage, both ischemic and direct toxic.
 Aim. To evaluate the role of NGAL and KIM-1 in urine as early markers of cisplatin nephrotoxicity.
 Materials and methods. The study included 50 patients treated with cisplatin in combination with fluoropyrimidines or paclitaxel. Prior to treatment and over a period of 8 weeks, the Friedman test was used to assess blood pressure, plasma creatinine, potassium, urea levels, daily proteinuria, urine NGAL and KIM-1 levels, and glomerular filtration rate (GFR). ROC analysis was used to assess the prognostic significance of NGAL and KIM-1 in the development of nephrotoxicity.
 Results. There was a statistically significant increase in the level of urea (=17.7; df 4, p=0.001), potassium (=42; df 4, p0.001), a decrease in GFR (=32.3; df 4, p0.001), the appearance of proteinuria (=50.4; df 4, p0.001). The concentration of NGAL and KIM-1 increased already one week after the start of cisplatin therapy, reaching a maximum by 8 weeks (=200; df 4, p0.001). The appearance of NGAL at a concentration of 10.743 ng/ml and KIM-1 at a concentration of 182.4 pg/ml in the first week after administration of cisplatin allows predicting the development of nephrotoxicity by the 8th week with high sensitivity (90.91%) and specificity (94.87%), AUC 0.96.
 Conclusion. The appearance of NGAL and KIM-1 in urine already in the first week of treatment allows predicting the development of nephrotoxicity a decrease in GFR of less than 60 ml/min by the 8th week of therapy with high sensitivity and specificity. Both biomarkers can be considered early prognostically significant.

Neutrophil Gelatinase-Associated Lipocalin Profile in Critically Ill Patients with Decreased of Consciousness

Background
 Neutrophil Gelatinase-Associated Lipocalin (NGAL) is an early marker of renal tubules damage. In critically ill patients,there are significant oxygenation disruptions to many organs particularly the kidneys and the brain. Early recognition of renal abnormalities in patients with a decreased of consciousness may improve the outcomes of these patients.
 
 Objective
 To observe the profile of Neutrophil Gelatinase-Associated Lipocalin in critically ill children with a decreased level of consciousness in Hasan Sadikin Hospital Bandung.
 
 Method
 A cross-sectional study was performed on critically ill children with a decreased of consciousness in Hasan Sadikin Hospital, Bandung.
 
 Result
 Fifty-nine patients aged 2-15 years old were included in the study. There were thirty-seven males (62.7%) and twenty-two females (37.2%). In this study, all critically ill patients had elevated urinary NGAL levels with an average value of 606.95 ng/mL (1.20 -24629.59 ng/mL). We found that 30% of these patients developed sepsis caused by various etiologies which mostly were malignancy in 22 patients (37.3%) and pneumonia in 14 patients (23.7%). Of all the patients, 16.9% showed clinical improvement.
 
 Summary
 Neutrophil Gelatinase-Associated Lipocalin level is elevated in critically ill patients with a decreased of consciousness.

Serum and Urinary Neutrophil Gelatinase-Associated Lipocalin Are Not Associated With Serum Redox Parameters in Amateur Athletes After an Ultramarathon.

ObjectiveTo evaluate the relationship between oxidative stress and NGAL levels in blood and urine of amateur athletes after participating in a 100 km ultramarathon.MethodologyThe sample was composed of seven athletes, submitted to anthropometric assessment, cardiopulmonary exercise test, collection of urine and blood, measurement of body weight. The rate of perceived exertion (RPE), competition duration, heart rate (HR), energy expenditure and oxygen consumption (V’O2”) were also measured during the event. The energy consumption during the race was verified at its end. The analyses were based on the means (M) and respective standard deviations (SD), with statistical significance set at 5% (p < 0.05). Paired t-test was used for comparison between the periods before and after the competition, and Pearson’s correlation coefficient was used to measure the linear correlation between quantitative variables.ResultsBody mass index (BMI) of the sample was 25.75 kg/m2 ± 3.20, body fat percentage 18.54% ± 4.35% and V’O2”max 48.87% ± 4.78. Glucose, cortisol, and neutrophil gelatinase-associated lipocalin (NGAL) (p < 0.01) as well as glutathione peroxidase (GPx) active were higher after the race when compared to basal values. Moreover, lactate, creatinine, microalbuminuria, and glomerular filtration rate (GFR) (p < 0.001) were also higher after the race. After the competition, there was a significant correlation only between serum NGAL and creatinine, which was classified as strong and positive (r: 0.77; p < 0.05). There was a significant reduction (p < 0.05) of body weight after the event (72.40 kg ± 9.78) compared to before it (73.98 kg ± 10.25). In addition, we found an increase of RPE (p < 0.001) after the race. The competition lasted 820.60 min (±117.00), with a 127.85 bpm (±12.02) HR, a 2209.72 kcal ± 951.97 energy consumption, 7837.16 kcal ± 195.71 energy expenditure, and 28.78 ml/kg/min–1 (±4.66) relative V’O2”max.ConclusionThe lack of correlation between oxidative stress biomarkers and serum and urine NGAL suggests that NGAL is more sensitive to inflammatory processes than to ROS levels.

Serum and Urinary Neutrophil Gelatinase-Associated Lipocalin Levels as Early Markers of the Renal Function in Patients With Urinary Stone-Induced Hydronephrosis.

IntroductionUrinary stones cause hydronephrosis, which leads to kidney function impairment. The serum creatinine level is frequently used as a marker of kidney function. However, in some patients with hydronephrosis, it does not reflect the kidney function changes in the early stages of kidney stone disease. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel indicator of the kidney function. Previous NGAL-related research has focused on its role in acute kidney injury. This study aimed to determine the usefulness of NGAL as an early marker of the kidney function in patients with urinary stones and hydronephrosis.MethodsEighty-five patients with urinary stones who were admitted to the Shanghai Tenth People's Hospital (USP group) and 65 healthy volunteers (NC group) were recruited. Blood and urine samples collected from the study participants were evaluated using an enzyme-linked immunosorbent assay to determine the NGAL concentration. Data on the height, weight, age, medical history, and blood and urine findings were collected. Computed tomography data were collected from the USP group.ResultsCompared to in the NC group, NGAL levels were significantly elevated in the USP group (P < 0.001). However, no significant differences in the NGAL levels were observed among the USP group members with different degrees of hydronephrosis. Furthermore, no significant between-group differences in the creatinine level or the estimated glomerular filtration rate were observed. The areas under the receiver operating characteristic curves for the serum and urinary NGAL levels with hydronephrosis were 92.03 and 99.54%, respectively. The areas under the receiver operating characteristic curves for the serum and urinary NGAL levels with kidney stones were 85.05 and 91.89%, respectively.ConclusionNGAL is a sensitive indicator of hydronephrosis secondary to urinary stones.

The combined effects of exercise-induced muscle damage and heat stress on acute kidney stress and heat strain during subsequent endurance exercise.

The purpose of the study was to investigate the combined effect of downhill running and heat stress on muscle damage, as well as on heat strain and kidney stress during subsequent running in the heat. In a randomized cross-over study, ten non-heat-acclimated, physically active males completed downhill running in temperate (EIMD in Temp) and hot (EIMD in Hot) conditions followed by an exercise-heat stress (HS) test after 3-h seated rest. Blood and urine samples were collected immediately pre- and post-EIMD and HS, and 24h post-EIMD (post-24h). Core temperature and thermal sensation were measured to evaluate heat strain. Serum creatine kinase (CK), maximal voluntary isometric contraction of the quadriceps (MVC) and perceived muscle soreness were measured to evaluate muscle damage. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels were measured to indicate acute kidney stress. CK, MVC and perceived soreness were not different between conditions at any timepoints. In the EIMD in Hot condition, urinary NGAL was significantly elevated from pre- to post-HS (pre-HS: 6.56 {1.53-12.24}ng/min, post-HS: 13.72 {7.67-21.46}ng/min, p = 0.034). Such elevation of NGAL or KIM-1 was not found in the EIMD in Temp condition. As compared with downhill running in a temperate environment, downhill running in a hot environment does not appear to aggravate muscle damage. However, elevated NGAL levels following EIMD in a hot environment suggest such exercise may increase risk of mild acute kidney injury during subsequent endurance exercise in the heat.

Preventive effects of different doses of atorvastatin on contrast-induced acute kidney injury in patients after multiple CT perfusions

The purpose of this clinical trial was to evaluate the preventive effects of different doses of atorvastatin on CI-AKI in patients after CT perfusions. 688 patients undergoing CT perfusions were administered doses of atorvastatin (20 mg/day, n = 164), atorvastatin (40 mg/day, n = 178), atorvastatin (60 mg/day, n = 176) and placebo (40 mg/day, n = 170). Several factors, urinary neutrophil gelatinase-associated lipocalin (NGAL) levels, protein kinase C (PKC), nuclear factor erythroid-2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate (NADPH) responsible for contrast-induced acute kidney necrosis were recorded in this study. Postoperative administration of atorvastatin decreased the risk of CI-AKI and improved renal function. 60 mg/day of atorvastatin showed best preventive effect on CI-AKI in three groups determined by Charlson Cormobidity Index (CCI) and risk, injury, failure, loss, end-stage renal disease (RIFLE). 60 mg/day of atorvastatin significantly decreased the inflammatory cytokines interleukin (IL)-1β, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α compared to 20 mg/day and 40 mg/day of atorvastatin in patients after multiple CT perfusions. NADPH oxidase 4 (NOX4) and p22phox expression was reduced by atorvastatin treatment. In conclusion, these outcomes indicate that 60 mg/day of atorvastatin treatment reduces the risk of CI-AKI in patients after multiple CT perfusions.

Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion.

Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury.

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

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

The Utility of Neutrophil Gelatinase-Associated Lipocalin in the Detection of Emerging Lung Injury due to Mechanical Ventilation in Children: A Preliminary Study

Objective:Lung injuries are mostly ignored in patients supported by mechanical ventilation. Neutrophil gelatinase-associated lipocalin has come into prominence as an early sensitive and highly predictive biomarker of inflammation. The purpose of the study was to assess the capability of neutrophil gelatinase-associated lipocalin in recognizing lung injuries in children requiring mechanical ventilation.Materials and Methods:This prospective case-controlled study was carried out in a tertiary pediatric intensive care unit. The entire study group consisted of a total of 45 patients, 15 in the patient group (supported by invasive mechanical ventilation) and 30 in the control group (self-breathing). Whether lung injuries developed or not was investigated by measuring serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin levels in the course of ventilation support.Results:In the patient group supported by mechanical ventilation, mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were measured as 192 ± 136.7 ng/mL and 43.7 ± 57.5 ng/mL, respectively. In the control group (self-breathing patients), mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were found as 144.8 ± 95 ng/mL and 39.3 ± 85 ng/mL, respectively. The levels of serum-neutrophil gelatinase-associated lipocalin were higher in those ventilated mechanically, compared to self-breathing patients. Although urine-neutrophil gelatinase-associated lipocalin levels were higher among mechanically ventilated patients than the controls, the difference was not statistically significant.Conclusion:Based on our study findings, we consider that neutrophil gelatinase-associated lipocalin may be a useful biomarker for emerging lung injuries due to mechanical ventilation in critically ill children and deserves to be investigated.

Role of Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) in various types of hepatorenal syndrome (HRS) based on New definition

Background and Aim: Hepatorenal syndrome in cirrhosis is known for many years. Recently definition and subgroup of the hepatorenal syndrome had been updated. So, we conducted this study to evaluate the role of neutrophil gelatinase-associated lipocalin (NGAL) in a group of patients divided based on a new definition. Methods: We have enrolled 62 consecutive patients with cirrhosis with HRS based on new criteria given by Angeli et al.'s in their position paper. Patients were also subcategorized into three groups- HRS- AKI, HRS-AKD, and HRS-CKD. Urinary NGAL was measured on Day 3 of admission Results: Among 62 patients, the majority of patients were having HRS-AKI (49 patients, 79%). While 8 patients and 5 patients were having HRS-AKD and HRS-CKD. Urinary neutrophil gelatinase-associated lipocalin (NGAL) was higher in HRS-AKI than in HRS-AKD and HRS-CKD (Median- 463.6 vs 212.2 vs 53 drug/L respectively). Also, urinary NGAL was significantly higher in patients with persistent AKI (18 patients) than transient AKI (31 patients) (421 ± 322 vs 267 ± 188 drug/L). Overall mortality in the HRS-AKI group was 35.7% (31/49 patients). Urinary NGAL level in deceased patients with HRS-AKI was significantly higher than in survived patients (521 345 vs 260 ± 170 drug/L, p-value- 0.04). Conclusions: NGAL measured on day 3 is an important predictor of renal outcome and survival in patients with cirrhosis.

The Utility of Neutrophil Gelatinase-Associated Lipocalin in the Detection of Emerging Lung Injury due to Mechanical Ventilation in Children: A Preliminary Study.

Lung injuries are mostly ignored in patients supported by mechanical ventilation. Neutrophil gelatinase-associated lipocalin has come into prominence as an early sensitive and highly predictive biomarker of inflammation. The purpose of the study was to assess the capability of neutrophil gelatinase-associated lipocalin in recognizing lung injuries in children requiring mechanical ventilation. This prospective case-controlled study was carried out in a tertiary pediatric intensive care unit. The entire study group consisted of a total of 45 patients, 15 in the patient group (supported by invasive mechanical ventilation) and 30 in the control group (self-breathing). Whether lung injuries developed or not was investigated by measuring serumneutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin levels in the course of ventilation support. In the patient group supported by mechanical ventilation, mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were measured as 192 ± 136.7 ng/mL and 43.7 ± 57.5 ng/mL, respectively. In the control group (self-breathing patients), mean levels of serum-neutrophil gelatinase-associated lipocalin and urine-neutrophil gelatinase-associated lipocalin were found as 144.8 ± 95 ng/mL and 39.3 ± 85 ng/mL, respectively. The levels of serum-neutrophil gelatinase-associated lipocalin were higher in those ventilated mechanically, compared to self-breathing patients. Although urineneutrophil gelatinase-associated lipocalin levels were higher among mechanically ventilated patients than the controls, the difference was not statistically significant. Based on our study findings, we consider that neutrophil gelatinase-associated lipocalin may be a useful biomarker for emerging lung injuries due to mechanical ventilation in critically ill children and deserves to be investigated.

Comparison of Neutrophil Gelatinase-associated Lipocalin and Renal Resistive Index as Acute Kidney Injury Predictor in Critically Ill Patients at ICU H. Adam Malik Hospital Medan

BACKGROUND: Acute kidney injury (AKI) is a complication found in critically ill patients. Current consensus explains that diagnosis of AKI based on increased serum creatinine and decreased urine output. Neutrophil gelatinase-associated lipocalin (NGAL) level is increased a few hours after tubular damage occurred and can predict AKI more significantly than serum creatinine. Renal resistive index (RRI) is also a good marker in predicting the early stage of AKI. AIM: This study aimed to compare RRI and NGAL level as marker to predict incidence of AKI in critically ill patients treated in the Intensive Care Unit (ICU) at H. Adam Malik Hospital Medan. METHODS: This was an observational prospective cohort study and conducted in ICU at H. Adam Malik Hospital Medan in April-May 2021. This study had been approved by the Ethics Committee of Faculty of Medicine, Sumatera Utara University and H. Adam Malik Hospital Medan. Inclusion criteria are critical patients aged 18–65 years with 1st and 2nd priority level. Consecutive sampling was used. Resistive Index (RI) measured using USG Doppler by researcher and the results confirmed by ICU supervisors, while urine NGAL level measured within 3 h after ICU admission. Plasma urea and creatinine level measured after 24h after ICU admission. RESULTS: A total of 40 samples were collected; percentage of men and women are 66–35%, respectively (p = 0.001). There was a significant difference RI between AKI-group and non-AKI group (0.719 ± 0.060 and 0.060 ± 0.077, respectively) (p = 0.001). RI has a sensitivity of 71%, specificity of 84%, and accuracy of 87% in predicting occurrence of AKI with AUROC = 0.873. Meanwhile, NGAL has a sensitivity, specificity, and accuracy (66%, 89%, 78%, respectively) in early prediction of AKI incidence in critically ill patients. CONCLUSION: RI value was higher in AKI group than non-AKI group. RRI has better sensitivity than NGAL in predicting incidence of AKI.

Reference interval for urinary neutrophil gelatinase-associated lipocalin in healthy adults in Jiangsu region in Eastern China: amulticenter 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 <87.5ng/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.

Urinary NGAL is a Potential Biomarker for Early Renal Injury in Insulin Resistant Obese Non-diabetic Children

Objective:Neutrophil gelatinase-associated lipocalin (NGAL) is one of the new biomarkers for detecting acute renal injury. There are studies showing the relationship between NGAL and renal injury in obese children. The aim of this study was to investigate whether urinary levels of NGAL, kidney injury molecule-1, and serum cystatin C are increased in insulin resistance (IR) patients before the development of diabetes.Methods:Cross-sectional, case-controlled study that included non-diabetic obese children and adolescent patients with IR and a non-diabetic obese control group with no IR, who attended a tertiary center pediatric endocrinology outpatient clinic between 2016-2018. Those with diabetes mellitus and/or known renal disease were excluded. NGAL and creatinine (Cr) levels were evaluated in the morning spot urine from all participants. Serum renal function was evaluated.Results:Thirty-six control and 63 IR patients were included in the study, of whom 68 (68.7%) were girls. The mean age of all participants was 13.12±2.64 years and no statistically significant difference was found between the two groups in terms of age or gender distribution. Median (range) spot urinary NGAL (u-NGAL) values in the IR group were significantly higher at 26.35 (7.01-108.7) ng/mL than in the control group at 19.5 (3.45-88.14) ng/mL (p=0.018). NGAL/Cr ratio was also significantly higher in the IR group compared to the control group (p=0.018).Conclusion:Obese pediatric patients with IR were shown to have elevated levels of u-NGAL, a marker of renal injury. u-NGAL examination may show early renal injury before development of diabetes.

Profiling Biomarkers in HIV Glomerular Disease - Potential for the Non-Invasive Diagnosis of HIVAN?

BackgroundThere is a wide spectrum of kidney pathology in human immunodeficiency virus (HIV) infection, affecting all structures of the kidney. The histology of HIV chronic kidney disease (CKD) is diverse, ranging from HIV-associated nephropathy (HIVAN) to focal glomerulosclerosis (FSGS), HIV-immune complex disease (HIV-ICD), other glomerulopathies and tubulo-interstitial nephritis. Definitive diagnosis is by kidney biopsy, an invasive procedure. However, serum and urinary biomarkers may be useful in predicting the histological diagnosis of HIVAN.PurposeWe wished to determine the utility of serum and urinary biomarkers in predicting the histological diagnosis of HIVAN.Patients and MethodsWe measured neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, transforming growth factor (TGF)-β isoforms and bone morphogenetic protein (BMP)-7 in the serum and urine in patients with different histological forms of HIV glomerular disease.ResultsIn HIVAN, we demonstrated increased levels of serum cystatin C and increased levels of serum and urinary NGAL. Urinary TGF-β1 and TGF-β2 levels were elevated in HIV-positive patients with CKD but were not significantly different in the different HIV histologies, while urinary BMP-7 levels were elevated in minimal change disease.ConclusionThis study confirmed the presence of increased serum and urinary biomarkers of tubular injury in patients with HIVAN, and increased urinary biomarkers of fibrosis in HIV CKD, and may indicate their value as a non-invasive diagnostic tool for the diagnosis of HIVAN.

The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria.

The sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of glucose-lowering drugs for individuals with diabetes. Large-scale clinical trials indicated that SGLT2 inhibitors have both a cardiovascular-protective and renal-protective effects. A reduction in glomerular hyperfiltration and a decrease in albuminuria are suspected as the main causes of SGLT2 inhibitors' renoprotective effect. The effects of SGLT2 inhibitors on tubular damage in non-albuminuric diabetic patients are unclear. The SGLT2 inhibitor tofogliflozin (20mg, 1 × /day) was orally administered to 14 non-albuminuric diabetic patients. Serum and urine samples were collected at baseline (before) and after the start of tofogliflozin treatment. Hemoglobin A1c, hemoglobin, estimated glomerular filtration rate (eGFR), body weight, and blood pressure (BP) were analyzed as clinical parameters at baseline and 1, 3, and 6months later. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-β-D-glucosaminidase were measured as tubular damage markers and the urinary 8-hidroxydeoxyguanosine (8-OHdG) values were measured as an oxidative stress marker at baseline and at 1 and 3months. Compared to baseline, the patients' HbA1c values and body weights were significantly decreased post-tofogliflozin administration, and their eGFR values were decreased at 3months but recovered at 6months; the hemoglobin concentrations were significantly increased at 3 and 6months and the urinary NGAL level tended to be decreased at 3months. No significant changes in blood urea nitrogen, BP, NAG, urine sodium concentration, or urinary 8-OHdG values occurred. The effect of this SGLT2 inhibitor was not influenced by the use of an angiotensin receptor blocker or dipeptidyl-peptidase 4 inhibitor. For individuals with non-albuminuric diabetes, tofogliflozin has a good glucose-lowering effect and might have a tubular-protective effect.

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis. MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI. ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01). ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.