uNGAL Levels Research Articles

Plasma and Urinary Neutrophil Gelatinase-Associated Lipocalin as Predictors of Renal Parenchymal Involvement in Children with Febrile Urinary Tract Infection: A Pilot Study.

Urinary tract infections (UTIs) are very common bacterial infections in children. Early detection of renal parenchymal involvement in this setting can help clinicians make more effective treatment choices. The aim of this pilot study was to assess the ability of plasma and urinary neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL) levels, measured using an automated system, to accurately predict renal parenchymal involvement in children with febrile UTIs. This prospective single-center study included 28 children aged ≥ 4 years with a first episode of febrile UTIs. All patients underwent magnetic resonance imaging. pNGAL, uNGAL, procalcitonin, C-reactive protein (CRP), and white blood cells were measured before antibiotic therapy. The receiver operating characteristic (ROC) area under the curve for predicting acute pyelonephritis was 0.6 for pNGAL, 0.8 for CRP, 0.4 for PCT, and 0.4 for uNGAL. The ROC analyses showed an optimal cutoff of 141.0 ng/mL for pNGAL (sensitivity, 54.2%; specificity, 75.0%; positive predictive value, 92.9%; and negative predictive value, 21.4%). pNGAL and uNGAL did not effectively aid the early prediction of renal parenchymal involvement in children ≥ 4 years with febrile UTIs. The novelties of this study were the use of MRI as the gold standard and an automated biochemical method to measure NGAL.

Urinary cystatin-C and urinary NGAL associated with sepsis predicts longer hospital stay in premature newborns.

Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30days (odds ratio: 1.052; 95% CI: 1.012-1.093; p=0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.

Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone.

In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial. Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, with death treated as a competing event. Risk factors considered were age, sex, mean arterial pressure, white blood cell count, albumin, MELD, ascites, HE, and treatment arm. At baseline, no participants had AKI; 33% (n=49) developed AKI during follow-up. AKI incidence was higher in A+Z than in PRED (45% [n=33] versus 22% [n=16], p =0.001). AKI phenotypes were similar between the 2 treatment arms ( p =0.361), but peak AKI severity was greater in A+Z than PRED (stage 3 n=21 [63.6%] vs. n=8 [50.0%], p =0.035). At baseline, urine-neutrophil-gelatinase-associated lipocalin levels were similar between participants who developed AKI in both treatment arms ( p =0.319). However, day 7 and 14 urine-neutrophil-gelatinase-associated lipocalin levels were significantly elevated in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI ( p =0.002 and 0.032, respectively). On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35, p =0.005). AKI occurred more frequently and was more severe in participants treated with A+Z. A+Z-treated participants with AKI had higher urine-neutrophil-gelatinase-associated lipocalin, suggesting that A+Z maybe nephrotoxic in patients with severe alcohol-associated hepatitis.

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis.

Early and accurate diagnosis of urinary tract infection (UTI) can prevent serious sequelae including chronic kidney disease. Multiple individual studies have identified urine neutrophil gelatinase-associated lipocalin (uNGAL) as a promising biomarker for early diagnosis of UTI. We sought to understand the distribution and diagnostic accuracy of uNGAL values in patients presenting with UTI symptoms. Our systematic literature reviews in PubMed, Embase, and Cochrane Reviews up to March 2024, identified 25 studies reporting mean/median, standard deviation/quartiles, and detection limits of uNGAL in symptomatic patients with and without culture-confirmed UTI. Seventeen studies were in children. Meta-analyses were performed using the quantile estimation (QE) method estimating the distributions of uNGAL, which were then compared between the UTI and non-UTI groups for identifying the best cut-off points maximizing the Youden index. Sensitivity analyses were performed on all 25 studies including adult patients. We found that uNGAL levels were significantly higher in samples with confirmed UTI compared to those without. In pediatric studies, median and 95% confidence interval (CI) of uNGAL values were 22.41 (95% CI of 9.94, 50.54) ng/mL in non-UTI group vs. 118.85 (95% CI of 43.07, 327.97) ng/mL in UTI group. We estimated the cut-off point of 48.43 ng/mL with highest sensitivity (96%) and specificity (97%) in children. Sensitivity analysis including both pediatric and adult studies yielded similar results. The level of uNGAL in symptomatic patients with confirmed UTI is much higher than that reported in patients without UTI. It may be used as a diagnostic tool to identify UTI early among symptomatic patients. The range of uNGAL concentrations and cut-off points reported in subjects with UTI is much lower than that reported in patients with acute intrinsic kidney injury. https://www.crd.york.ac.uk/, PROSPERO (CRD42023370451).

Combination of Urinary Neutrophil Gelatinase-associated Lipocalin, Kidney Injury Molecular-1, and Angiotensinogen for the Early Diagnosis and Mortality Prediction of Septic Acute Kidney Injury.

Acute kidney injury (AKI) is one of the most severe complications of sepsis. This study was conducted to analyze the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecular-1 (uKIM-1), and urinary angiotensinogen (uAGT) in the early diagnosis and mortality prediction of septic AKI. The prospective study enrolled 80 sepsis patients in the ICU and 100 healthy individuals and divided patients into an AKI group and a non-AKI group. uNGAL, uKIM-1, uAGT, serum creatinine/procalcitonin/C-reaction protein, and other indicators were determined, and clinical prediction scores were recorded. The sensitivity and specificity of uNGAL, uKIM-1, and uAGT in diagnosis and mortality prediction were analyzed by the receiver operator characteristic (ROC) curve and the area under the curve (AUC). uNGAL, uKIM-1, and uAGT levels were higher in sepsis patients than healthy controls, higher in AKI patients than non-AKI patients, and higher in AKI-2 and AKI-3 patients than AKI-1 patients. At 0 h after admission, the combined efficacy of three indicators in septic AKI diagnosis (ROC-AUC: 0.770; sensitivity: 82.5%; specificity: 70.0%) was better than a single indicator. At 24 h, uNGAL, uKIM-1, and uAGT levels were higher in sepsis non-survivals than survivals and higher in septic AKI non-survivals than septic AKI survivals. The combined efficacy of three indicators in the prediction of sepsis/septic AKI mortality (ROC-AUC: 0.828/0.847; sensitivity: 71.4%/100.0%; specificity: 82.7%/66.7%) was better than a single indicator. uNGAL, uKIM-1, and uAGT levels were increased in septic AKI, and their combination helped the early diagnosis and mortality prediction.

Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients. Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality. Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02). Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality.

Early kidney damage in diabetic adolescents with increased blood pressure and glomerular hyperfiltration.

The early impact of type 1 diabetes mellitus (DM1), increased blood pressure and glomerular hyperfiltration (GHF) on kidney damage in adolescents using two urinary markers of kidney injury - neutrophil gelatinase-associated lipocalin (uNGAL) and transferrin (uTransf) - was assessed. The study group consisted of 80 adolescents with DM1, of whom 42 were patients with increased blood pressure (IBP), and 38 were patients with normal blood pressure (NBP). Blood pressure was assessed by 24-hour ambulatory blood-pressure monitoring. All patients showed estimated glomerular-filtration rates (eGFRs) above 90 mL/min/1.73 m2. The control group consisted of 19 healthy, age and gender-matched adolescents. All diabetic children showed a significant increase in uNGAL (P<0.001). This increase was not related to blood pressure. The uNGAL was elevated in all patients with normal albuminuria, normal eGFR and NBP. The concentration of uTransf was not increased in the entire studied group and was not related to blood pressure. Children with GHF had significantly higher levels of both uTransf (P=0.010) and uNGAL (P<0.001). In patients with GHF, blood pressure was normal. Patients with IBP showed a significantly higher value for triglycerides (r=0.247; P=0.032) and a longer duration of diabetes (r=0.264; P=0.019). Diabetes is the leading risk factor for early kidney injury. However, increased blood pressure does not lead to kidney damage, at least in the early stage of DM1. The uNGAL is the early indicator of kidney injury and increases in patients with normal albuminuria, normal glomerular filtration and normal blood pressure. Glomerular hyperfiltration seems to be a marker of diabetic-kidney involvement.

Impact of low pneumoperitoneum on renal function and acute kidney injury biomarkers during robot-assisted radical prostatectomy (RARP): a randomised clinical trial

The objective of this study was to evaluate the effect of low pneumoperitoneum pressure (Pnp) on renal function and renal injury biomarkers during robot-assisted radical prostatectomy (RARP). A single-centre, triple-blinded, randomised clinical trial was conducted with 98 patients undergoing RARP, who were assigned to either standard Pnp of 12 mmHg or low Pnp of 7 mmHg. The primary outcome was urinary neutrophil gelatinase-associated lipocalin (u-NGAL), and several other kidney injury biomarkers were assessed as secondary outcomes. Acute kidney injury (AKI) was evaluated using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, the gold standard method for defining AKI. The trial was registered on ClinicalTrials.gov (NCT04755452). Patients in the low Pnp group had significantly lower levels of u-NGAL (mean difference − 39.9, 95% CI − 73.7 to − 6.1, p = 0.02) compared to the standard Pnp group. No significant differences were observed for other urinary biomarkers. Interestingly, there was a significant difference in intraoperative urine production between the groups (low Pnp median: 200 mL, IQR: 100–325 vs. standard Pnp median: 100 mL, IQR: 50–200, p = 0.01). Similarly, total postoperative urine production also varied significantly (low Pnp median: 1325 mL, IQR: 1025–1800 vs. standard Pnp median: 1000 mL, IQR: 850–1287, p = 0.001). The occurrence of AKI, as defined by the KDIGO criteria, did not differ significantly between the groups. Low Pnp during RARP resulted in lower u-NGAL levels, suggesting a potential benefit in terms of reduced renal injury. However, the lack of a notable difference in AKI as defined by the KDIGO criteria indicates that the clinical significance of this finding may be limited. Further research is needed to validate and expand on these results, ultimately defining the optimal Pnp strategy for RARP and improving patient outcomes.

Evaluation of urinary neutrophil gelatinase associated lipocalin in the early diagnosis of acute kidney injury with sepsis.

To assess the utility of urinary neutrophil gelatinase associated lipocalin (uNGAL) in the diagnosis of acute kidney injury (AKI) in the context of sepsis. In this retrospective study, a total of 142 patients with sepsis treated in the Third Hospital of Shanxi Medical University from January 2019 to January 2021 were included. Patients diagnosed with AKI complicated with sepsis were categorized into the AKI group (n=70 cases), and patients diagnosed with sepsis were classified into the non-AKI group (n=72 cases). We collected and analyzed data on serum creatinine (Scr) and uNGAL levels. The ROC (receivers operating characteristics) curve was used to evaluate the sensitivity and specificity of uNGAL in the diagnosis of AKI with sepsis. The level of uNGAL in the AKI group increased over time following admission, which was not observed in the non-AKI group. Twenty-four hours after admission, the level of uNGAL in the AKI group was significantly higher than that in the non-AKI group (P < 0.05), but there was no significant difference in Scr level between the two groups (P > 0.05). At 72 hours after admission, the AUC of uNGAL in predicting AKI was 0.989 (95% CI: 1.018-1.085), and its intercept value was 961.3 ng/ml. At the same time, the correlation analysis showed that the level of uNGAL was positively correlated with the occurrence of AKI. uNGAL is superior to Scr for early diagnosis of AKI patients with sepsis.

Correlation of Urinary Neutrophil Gelatinase with the Histopathological Extent of Kidney Damage in Patients with Diabetic Nephropathy.

Diabetic nephropathy (DN), a leading cause of chronic kidney disease, is known to develop in around 40% of patients with diabetes. NGAL, a biomarker expressed by the tubular epithelium, has been evaluated in both acute and chronic kidney injury. However, kidney damage revealed by the histology of renal tissue core biopsies has not been quantified by morphometry and its correlation with urinary NGAL (uNGAL) has not been studied. Our objective was to compare levels of uNGAL with the extent of kidney damage in the histopathological results of morphometry in patients with DN. This prospective analytical study was conducted in a tertiary hospital. Urine samples of 42 patients were collected and freeze-dried. uNGAL was estimated through a chemiluminescent microparticle immunoassay. Pearson's correlation coefficients between kidney damage quantified by morphometry and NGAL values were examined. The correlation of uNGAL with the percentage of acute tubular injury assessed by morphometry in the renal core was 7.35% (P = 0.64). uNGAL had the highest correlation with inflammation (r = 54.2%; P = 0.002). Another parameter with a significant correlation was glomerular sclerosis with r = 35.6% (95% confidence interval: 10%-60%) and an associated P = 0.02. UNGAL was strongly correlated with inflammatory kidney damage in patients with DN.

Effect of Angiotensin Receptor-neprilysin Inhibitor on Acute Kidney Injury in Patients With Acute Decompensated Heart Failure

Objective: The risk of acute kidney injury (AKI) is high in patients with acute decompensated heart failure (ADHF). The aim of this study is to analyze the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in diagnosing AKI in patients with ADHF and evaluate the therapeutic effect of angiotensin receptor-neprilysin inhibitor (ARNI) on AKI. Method: Sixty patients with ADHF were enrolled at the First Affiliated Hospital of Kangda College of Nanjing Medical University from January 2020 to June 2021, and randomized into 2 groups (ARNI group: 30 patients treated with tablets of sacubitril valsartan sodium; and angiotensin-converting enzyme inhibitor (ACEI) group: 30 patients treated with benazepril). The uNGAL level was measured immediately after as well as 1, 2, 3, and 7 d after hospital admission. The serum creatinine (sCr) level and estimated glomerular filtration rate (eGFR) were measured immediately as well as 2 and 7 d after hospital admission. The urine volume, dose of loop diuretics, and duration of hospital stay (DoHS) were recorded. Result: The most valuable diagnostic metric for AKI in patients with ADHF was the uNGAL level 1 d after hospital admission, which had a sensitivity of 0.94, specificity of 0.84, and optimal cutoff of 125.62 μg/L. In the presence of AKI, during the first 2 d, patients in the ARNI-AKI and ACEI-AKI groups showed an increase in the sCr level and a reduction in the eGFR level, but there was no significant difference between the 2 groups (P &gt; 0.05). After 7 d of treatment, the sCr level decreased and the eGFR level increased in both groups, with a significantly greater changes being observed in the ARNI-AKI group than in the ACEI-AKI group (P &lt; 0.05, respectively). In the absence of AKI, the difference in the sCr level and eGFR between the 2 groups was not significant. The DoHS ((11.25 ± 2.38) d vs. (14.11 ± 2.89) d), urinary microalbumin level ((22.95 ± 6.04) mg/L vs. (31.91 ± 2.18) mg/L), and daily dose of loop diuretics ((19.03 ± 3.04) mg/d vs. (23.62 ± 4.46) mg/d) were significantly lower in patients with AKI in the ARNI group than in the ACEI group (P &lt; 0.05, respectively). Conclusion: In patients with ADHF, uNGAL measurement enables the diagnosis of AKI earlier than that using the sCr level by 1 to 2 d. ARNI treatment reduced the sCr level, facilitated eGFR recovery, reduced the daily dose of loop diuretics, and decreased the DoHS compared with that in patients receive ACEI treatment.

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

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

The Ratio of Contrast Volume/Glomerular Filtration Rate and Urine NGAL Predicts the Progression of Acute Kidney Injury to Chronic Kidney Disease in Patients After Planned Percutaneous Coronary Intervention.

To evaluate the value of contrast volume/glomerular filtration ratio (Vc/eGFR ratio) and urine Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting the progression contract associated-acute kidney injury (CA-AKI) to chronic kidney disease (CKD) in planned percutaneous coronary intervention (PCI) patients. We examined 387 adult patients who had undergone planned percutaneous coronary intervention (PCI). We determined acute kidney injury (AKI) and chronic kidney disease (CKD) using the criteria set by the Kidney Disease: Improving Global Outcomes (KDIGO). We calculated the estimated glomerular filtration rate (eGFR) using the CKD-EPI formula based on serum creatinine levels. To determine the Vc/eGFR ratio, we considered the contrast medium volume and eGFR for each patient. Additionally, we measured urine NGAL levels using the ELISA method. The percentage of CA-AKI patients who developed CKD after planned PCI was 36.36%. Within the CA-AKI to CKD group, the Vc/eGFR ratio was 2.82, and uNGAL levels were significantly higher at 72.74 ng/mL compared to 1.93 ng/mL for Vc/eGFR ratio and 46.57 ng/mL for uNGAL in the recovery CA-AKI group. This difference was statistically significant (p<0.001). Diabetic mellitus, urine NGAL concentration, and Vc/eGFR ratio were found to be independent factors in the progression of CA-AKI to CKD. The Vc/eGFR ratio and uNGAL showed predictive capabilities for progressing CA-AKI to CKD with an AUC of 0.884 and 0.878, respectively. The sensitivity was 81.3% for both, while the specificity was 89.3% for Vc/eGFR ratio and 85.7% for uNGAL. The Vc/eGFR ratio and uNGAL were good predictors for CA-AKI to CKD in planned PCI patients.

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

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

Endothelial Injury in Paediatric Sepsis-associated Acute Kidney Injury

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

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) as markers of active lupus nephritis

Background and objectivesDespite much research about lupus nephritis, none of the urinary biomarkers has been proven to be truly reflecting lupus nephritis activity, response to treatment, or prognosis. We aimed to study urinary biomarkers in lupus nephritis and test their relation to kidney damage.Patients and methodsForty patients with systemic lupus erythematosus (SLE) were divided into two graoups: (1) lupus nephritis group with biopsy-proven proliferative lupus nephritis (classes III and IV) and who did not receive immunosuppressive drugs within the preceding 3 months except for glucocorticoids and (2) lupus non-nephritis group with SLE patients without any renal manifestation. We assessed disease activity by the SLE disease activity index. uNGAL, uKim-1, uNGAL to urinary creatinine excretion (mg/dl), and uKim-1 to urinary creatinine excretion were measured in random spot urine samples at the time of renal biopsy and 6 months after the induction therapy.ResultsThe LN group before treatment showed higher levels of uNGAL and uKIM-1 (P-value < 0.001). ROC analysis showed that uNGAL at level of > 59 has a 95 % sensitivity, a 100 % specificity, and an AUC = 0.996 in the ability to diagnose LN. While the uKIM-1 ROC showed that at level of > 1.6, it has an 85 % sensitivity, an 80 % specificity, and an AUC = 0.919. uNGAL and uKIM levels were significantly lower after treatment (P-value < 0.001). No significant correlations were found between urinary markers before and after treatment with other clinical, inflammatory, and serological markers of lupus nephritis.ConclusionuNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio can be used as a predictor and a marker of disease activity for lupus nephritis.Key Points• Renal biopsy is the current standard for diagnosis of lupus nephritis and none of the urinary biomarkers has been fully concluded to have a diagnostic power to reflect the activity or the response to treatment.• However, based on the finding of the current study, uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio showed significant diagnostic performance and were powerful indices of renal involvement in systemic lupus patients and as markers of disease activity.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

614: URINE BIOMARKERS, ACUTE KIDNEY INJURY, AND FLUID OVERLOAD IN INFANTS AFTER PEDIATRIC HEART SURGERY

Introduction: Acute kidney injury (AKI) and fluid overload (FO) are common in infants after heart surgery and are associated with increased morbidity and mortality. Urine biomarkers may allow for earlier diagnosis of AKI, but their role, time course, and association with FO in infants is incompletely characterized. We aim to characterize the association between urine neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM1), and cystatin C (uCysC) and AKI and FO in infants after heart surgery. Methods: We performed a single-center ancillary prospective cohort study of infants < 1 year old who underwent heart surgery and were enrolled in the STRESS trial (NCT03229538) from June 2019-May 2020. We excluded preterm infants and those who had preoperative AKI, as defined per the modified KDIGO criteria. Our primary outcome was development of any KDIGO defined AKI. Our secondary outcome was development of ≥10% FO 48 hours postoperatively. Urine samples were collected at three time points (preoperative, 0-< 8 hours post-bypass, 8-24 hours post-bypass). We examined the association between standardized urine biomarker values and AKI and FO using multivariable analysis controlling for demographics, surgical factors, and surrogate markers of illness severity. Results: Our cohort included 40 infants with a mean of 2 urine samples each. Median (IQR) age at surgery was 103 (5.5-161) days. A total of 22 (55%) infants were diagnosed with any AKI and 21 infants (53%) developed FO. No infant died. In unadjusted analysis, bypass time was longer (171 [106, 222] v 111 [75, 155] minutes, p=0.01), and vasoactive infusion score was higher (9.5 [6, 11.5] v 5 [2, 9.5], p=0.02) in infants with AKI compared to those without AKI. On multivariable analysis, higher levels of uCysC and uNGAL at 0-8 hours post-bypass were predictive of FO at 48 hours (OR:3.4; 95% CI: 1.3, 8.9; OR: 2.7; 95% CI: 1.2, 6.2, respectively). There was no significant correlation between uCysC, uNGAL, and uKIM1 at any time and AKI. Conclusions: In a single center cohort, uCysC and uNGAL in the early postoperative period were associated with FO at 48 hours postoperatively. UCysC, uNGAL, and uKIM1 were not associated with AKI. Further studies should focus on the role of urine biomarkers in early diagnosis of FO.

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Intensive Care Unit Admission Diagnosis: A Prospective Cohort Study.

Acute kidney injury (AKI) is most commonly caused by tubular injury and is associated with a wide variety of critical illnesses. It is well known that urinary biomarkers can lead to the early identification of AKI. However, the ability of urinary biomarkers to distinguish between different types of critical illness has been less studied. In this prospective cohort study, urinary neutrophil gelatinase-associated lipocalin (uNGAL) was measured in 107 patients consecutively admitted to the ICUs in our tertiary medical center. uNGAL samples were collected within 3-6 hours of admission to an ICU and measured by ELISA. All data were analyzed using R statistical software, and univariate analysis was used to determine the correlations of uNGAL levels with AKI stage, admission diagnoses, and ICU course. uNGAL level increased by a mean of 24-fold (SD 10-59) in ICU patients with AKI and demonstrated a significant correlation with the different AKI stages. uNGAL predicted the need for RRT, with values increased by more than 15-fold (P<0.05) in patients needing RRT, and remained a useful tool to predict AKI in ICU patients with a urinary tract infection. uNGAL level was correlated with certain ICU admitting diagnoses whereby uNGAL levels were lower in ICU patients with cardiogenic shock compared with other admission diagnoses (β=-1.92, P<0.05). uNGAL can be used as an early predictor of AKI and its severity in patients admitted to the ICU, including the need for RRT. uNGAL may also help in distinguishing patients with cardiogenic shock from those with other critical illnesses and identifying those at risk for poor outcomes irrespective of the presence of AKI.

Ureterorenoscopic (URS) Lithotripsy and Balloon Dilation Cause Acute Kidney Injury and Distal Renal Tubule Damage: A Prospective Study.

Ureterorenoscopy (URS) is believed to be a safe and effective procedure for treating ureteral stones or ureteral strictures. Rapidly increasing intrarenal pressure during URS may have a negative impact on the kidney, but its effect on renal function is not well known. The aim of this study was to evaluate whether URS balloon dilation or lithotripsy could cause acute kidney injury (AKI), which was evaluated using urine neutrophil gelatinase-associated lipocalin (NGAL), and renal tubular damage, which was evaluated using urine α-glutathione S-transferase (GST) and πGST. This prospective study included 207 patients with a mean age of 53.8 years between September 2012 and June 2013. Four groups were included: the ureteral stricture group (group 1), the ureteral stone group (group 2), and two control groups. URS increased urine NGAL (uNGAL) levels on days 1 and 14 in both groups, and only elevated uGST levels were noted on day 14 after URS lithotripsy (URS). On day 14, the difference between low-grade and high-grade hydronephrosis was significant in group 1 (p < 0.001) compared to that in group 2 (p = 0.150). Multivariate logistic regression analysis revealed that age, baseline estimated glomerular filtration rate (eGFR), and stone size > 1.0 cm were associated with the complete recovery of hydronephrosis after URS on day 14. Patients with ureteral stones with preserved renal function had more AKI than those with impaired renal function. However, there was no significant difference in URS-related AKI between the ≤1 cm and >1 cm subgroups. In addition, urine αGST and πGST levels were both significantly higher in the stone > 1 cm subgroup than in the ≤1 cm subgroup. In conclusion, URS laser lithotripsy and balloon dilatation resulted in AKI and renal tubular damage on day 14, although post-URS double-J (DBJ) stenting was performed in every patient.