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<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.

Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children

INTRODUCTION: The recommended therapeutic target for cefepime (FEP) is the time above MIC (fT>MIC). The frequency of target attainment and risk factor for sub-therapeutic concentrations in children have not been extensively studied. METHODS: We performed a prospective observational pilot study in children in our PICU receiving standard dosing of FEP for suspected sepsis (≥2 SIRS criteria). Three FEP concentrations were measured per subject and a urine sample was collected prior to PK sampling for measurement of urinary biomarkers. We used log linear regression to calculate the fT>MIC for each subject across a range of MIC values (1-16 µg/mL). We compared clinical factors/biomarkers between patients who did and did not achieve 100% fT>MIC for 8 µg/mL (cut-point for Pseudomonas) and tested the correlation between covariates and FEP troughs. RESULTS: 21 subjects were enrolled (median SIRS criteria: 3). PK sampling occurred after a median of 5 doses (range: 3-9). 43% of subjects achieved 100% fT>MIC for an MIC of 8 µg/mL. Younger age (p=.005), higher estimated GFR (p=.03), and lower urinary NGAL (p=.006) and KIM-1 (.03) were associated with failure to attain 100% fT>8 µg/mL. Age (r = 0.53), eGFR (r = -0.58), urinary NGAL (r = 0.42) and KIM-1 (r = 0.50) were significantly correlated with FEP troughs. CONCLUSIONS: A significant proportion of critically ill children failed to attain target concentrations for treatment of Pseudomonas aeruginosa with FEP. Younger patients and those with good kidney function (high GFR, low urinary biomarkers) may be at highest risk for subtherapeutic FEP concentrations.

Prognostic Role of Ngal In Critically Ill Patients

Background: Acute kidney injury (AKI) is a frequently encountered outcome in critically ill patients, accounting for increased mortality. Neutrophil gelatinase associated lipocalin (NGAL) has been of paramount importance as a novel biomarker of AKI. This study is an attempt to assess the use of NGAL in critically ill patients so that timely interventions can be done to reduce morbidity and mortality in such patients.Methods: A prospective observational study was conducted at SRN Hospital from August 1st 2020 to March 15th 2021, which included only critically ill patients with SOFA score>1 and requiring ICU admission. Patients of known renal diseases were excluded from the study. Blood as well as urinary samples for NGAL and other laboratory parameters were collected within 8 hours of admission. Patients who developed renal dysfunction were noted as our cases and the others were noted as controls. Results: The study was done on 125 patients, out of which 67 developed AKI while 58 did not develop AKI. Higher mortality was seen in patients with higher stage of AKI (P- 0.011). The cutoff of serum and urinary NGAL for predicting AKI were >42.3 ng/mL, >40.5 ng/mL respectively (P value <0.001). Hazard Ratio for all cause mortality of raised serum and urinary NGAL was 2.0062 (p value- 0.0001, 95% CI-1.0031 to 1.0092) and 2.0046 (p value-0.0035, 95% CI-1.0015 to 1.0078) respectively. Serum and urinary neutrophil gelatinase associated lipocalin at values >91 and >131 respectively were found to predict requirement of hemodialysis (p value<0.001).Conclusion: A single measurement of NGAL at the time of admission had good predictive ability for AKI. Higher values of NGAL were associated with staging of AKI and thus, correlated with need of hemodialysis. Furthermore, mortality was found to be associated with development of AKI and raised NGAL. Thus, NGAL maybe used to assess the prognosis of ICU patients so that patients at high risk may be managed aggressively, thus reducing mortality.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

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.

The Role of Urinary Biomarkers as Diagnostic and Prognostic Predictors of Acute Kidney Injury Associated With Vancomycin

Introduction: The incidence of acute kidney injury (AKI) related to vancomycin is variable, and several risk factors related to the treatment and patients may explain the nephrotoxicity. The role of urinary biomarkers in AKI related to vancomycin is unknown.Objective: The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic predictors of AKI related to vancomycin.Methods: A prospective cohort study of patients receiving vancomycin and admitted to wards of a public university hospital from July 2019 to May 2020 was performed. We excluded patients that had AKI before starting vancomycin, hemodynamic instability, inability to collect urine, and chronic kidney disease stage 5.Results: Ninety-four patients were included, and the prevalence of AKI was 24.5%, while the general mortality was 8.7%. AKI occurred 11 ± 2 days after the first vancomycin dose. The most frequent KDIGO stage was 1 (61%). There was no difference between patients who developed and did not develop AKI due to gender, length of hospital stay, dose, and time of vancomycin use. Logistic regression identified age (OR 6.6, CI 1.16–38.22, p = 0.03), plasmatic vancomycin concentrations between 96 and 144 h (OR 1.18, CI 1.04-1.40, p = 0.04), and urinary NGAL levels between 96 and 144 h (OR 1.123, CI 1.096–1.290, p = 0.03) as predictors of AKI. The time of vancomycin use (OR 4.61, CI 1.11–22.02, p = 0.03), higher plasmatic vancomycin concentrations between 192 and 240 h (OR 1.02, CI 0.98–1.06, p = 0.26), and higher cell cycle arrest urinary biomarkers TIMP-2 multiplied by IGFBP-7 between 144 and 192 h (OR 1.33, CI 1.10–1.62, p = 0.02; OR 1.19, CI 1.09–1.39, p = 0.04, respectively) were identified as prognostic factors for non-recovery of kidney function at discharge.Conclusion: AKI related to vancomycin was frequent in patients hospitalized in wards. Age, plasmatic vancomycin concentrations, and NGAL between 96 and 144 h were identified as predictors of AKI related to vancomycin use. Plasmatic vancomycin concentrations and urinary NGAL were predictors of AKI diagnosis within the next 5 days. The urinary biomarkers of cell cycle arrest TIMP-2 and IGFBP-7 and the duration of vancomycin use were associated with non-recovery of kidney function at hospital discharge moment.

Urinary Neutrophil Gelatinase-Associated Lipocalin in Type 1 and Type 2 Hepatorenal Syndrome and Its Correlation with Kidney Function

Objective: To determine the difference in urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) levels ​​in type 1 and type 2 Hepatorenal Syndrome (HRS) and determine the correlation between urinary NGAL and kidney function and the degree of liver disease severity in HRS patients. Methods: A total of 26 patients consisting of 13 patients in each group, both in type 1 and type 2 HRS at Adam Malik Hospital, Medan City, Indonesia. Urine samples were taken for NGAL examination using the ELISA method. A blood sample is used to assess kidney function. Liver disease severity was measured using the Child-pugh score. Data were analyzed using statistical t-test independent and Pearson correlation test. A p value less than 0.05 was applied to each statistical test as significant. Result: Total subjects consisted of 18 men and 8 women, with a mean age 57.5±8.91 years old. Hepatitis B virus was the most common etiology of liver cirrhosis in this study (53.8%) and the most degree of liver disease severity was Child-pugh C (65.4%). Urinary NGAL levels in type 1 HRS is significantly higher than type 2 (155.71±43.04 vs 105.85±32.32 ng/ml, p = 0.003). There was a positive correlation between uNGAL and serum creatinine (r = 0.488, P = 0.006). There was a positive correlation between uNGAL and Child-pugh score (r = 0.466, P = 0.008). Conclusion: Urinary NGAL level in type 1 HRS is higher than type 2, there is a positive correlation between uNGAL and serum creatinine and Child-pugh score in HRS patients. Keywords: Hepatorenal syndrome, urinary NGAL, Liver cirrhosis, kidney function.

Can Urinary KIM-1 and NGAL Predict Management Endoscopic Surgery in Acute Unilateral Obstructive Stone Disease? Results from a Prospective Cohort Study

<b><i>Introduction:</i></b> Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are the leading novel biomarkers used efficiently in acute kidney injury (AKI). The levels of these biomarkers increase especially in the early period of nephrotoxic and ischemic renal damage. In this study, we aimed to investigate the clinical importance of NGAL and KIM-1 biomarkers used in the effective evaluation of kidney functions in patients with acute unilateral obstructive stone disease (AUOSD) in the management of endoscopic surgery. <b><i>Materials and Methods:</i></b> We prospectively included patients who underwent endoscopic surgery due to AUOSD between January 2018 and December 2019. Urine KIM-1 and NGAL values of the patients were measured preoperative period, postoperative 4th h, and postoperative 7th day. The patients were evaluated according to the location and size of the stone, the degree of renal hydronephrosis, the duration of the operation, complications, and JJ stent placement. <b><i>Results:</i></b> The study enrolled 50 patients. Urinary KIM-1/Cr and urinary NGAL/Cr ratios were higher in postoperative 4th h than in others (<i>p</i> &#x3c; 0.001). Also, we found that urinary KIM-1/Cr and urinary NGAL/Cr ratios with Grade 2 and higher hydronephrosis were statistically higher than Grade 0–1 hydronephrosis (<i>p</i> &#x3c; 0.001 and <i>p</i>: 0.042, respectively). Additionally, a preoperative urinary KIM-1 value of 1.24 ng/mL had a sensitivity of 78% and a specificity of 63% to predict the presence of hydronephrosis. When urine KIM-1 and NGAL results were compared with surgery time, stone size and location, serum creatinine (sCr) value, and Post-Ureteroscopic Lesion Scale grade, the difference was not statistically significant. Postoperative 7th day NGAL/Cr and KIM-1/Cr ratios were statistically higher in those with JJ stents placed (<i>p</i>: 0.03 and <i>p</i>: 0.004, respectively). <b><i>Conclusion:</i></b> KIM-1 and NGAL can be used in our assessment of renal function in patients with AUOSD, even if sCr is normal. Also, these biomarkers can predict the presence of hydronephrosis. It can be helpful in determining the time of surgical treatment, as well as providing information in the follow-up of patients with JJ stents after treatment.