Urinary Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

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.

Microalbuminuria and Urinary Neutrophil Gelatinase-associated Lipocalin (uNGAL) in Human Immunodeficiency Virus Infected Children.

Introduction:Renal dysfunction and progression to end stage renal disease is well known in human immunodeficiency virus (HIV) infection. We studied the role of microalbuminuria and urinary NGAL levels in children with HIV infection for the prediction of renal dysfunction.Design and Methods:A cross-sectional study was carried out and 60 HIV infected children, aged (18 months to 15 years) were screened for microalbuminuria by nephelometry and for uNGAL by ELISA. Thirty healthy children were screened for uNGAL for normative data in Indian children.Results:The prevalence of microalbuminuria in studied population was 3.3%. The mean uNGAL and uNGAL/creatinine in study population was higher than controls (26.94 ± 93.12 ng/ml vs. 88.94 ± 345.20 mcg/g, and 15.53 ± 37.52 ng/ml vs. 30.12 ± 78.66 ng/ml; P = 0.003, P = 0.002). Children with lower CD4 counts had significant higher mean Albumin Creatinine Ratio (ACR) and mean uNGAL; P = 0.03, P = 0.01.Conclusions:uNGAL and urine microalbumin are useful biomarkers of early tubular and glomerular injury in children with HIV infection.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia

To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P=.026). Mortality was greater in neonates with AKI (25% vs 2%; P=.012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48hours of life. Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

Combination of hepcidin with neutrophil gelatinase-associated lipocalin for prediction of the development of sepsis-induced acute kidney injury

Background and aimsThe early prediction of the development of acute kidney injury (AKI) in critically ill patients with sepsis would facilitate early effective intervention. Recently, interest has focused on the biomarkers for AKI-linked iron metabolism. This study aimed to assess the early predictive values of hepcidin, neutrophil gelatinase-associated lipocalin (NGAL), and their combination for secondary AKI in patients with sepsis. Materials and methodsA prospective cohort study was performed in septic patients. Serum and urine hepcidin, and urine NGAL were analyzed at admission. The primary outcome measure was occurrence of sepsis-induced AKI based on 2011 Kidney Disease: Improving Global Outcomes (KDIGO) criteria during the first week of ICU stay. ResultsOf the 90 patients analyzed finally in the study, 44 (48.9%) patients developed AKI. Patients with AKI occurrence were more likely than those without AKI to have higher serum hepcidin and urine NGAL levels at admission (P < 0.01). Higher concentrations of these biomarkers were each independent predictor of the development of AKI in critically septic patients within the first week of their ICU stay. Serum hepcidin and urine NGAL (AUROC 0.787, 95% CI 0.688 to 0.8660 and AUROC 0.729, 95% CI 0.625 to 0.818, respectively) were comparable predictive indicators of AKI occurrence (P = 0.43 for DeLong’s test). Combining both biomarkers increased the AUROC to 0.828(95% CI 0.733 to 0.899), and this performance was statistically significantly better than urine NGAL alone (P = 0.03 for DeLong’s test). ConclusionSerum hepcidin measured at admission predicts the development of AKI similarly to urine NGAL. However, serum hepcidin adds significant accuracy to this prediction in combination with urine NGAL alone and has a good predictive value in patients with sepsis. Larger studies are needed to validate and explain these findings.

Early kidney injury in immunoglobulin A vasculitis: Role of renal biomarkers.

We aimed to determine whether urine kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) can be used as early noninvasive biomarkers of kidney injury in immunoglobulin A vasculitis. Patients who were diagnosed with immunoglobulin A vasculitis were included in the study. Urine samples were collected for determination of urine KIM-1 and NGAL levels. The control group consisted of age-matched healthy children. Sixty-one patients who were diagnosed with immunoglobulin A vasculitis were included in the study; 37.7% of these patients were determined to have renal involvement. Median KIM-1 was found to be significantly higher in the patient group (69.59pg/mL) than the control group (40.84pg/mL) (P = 0.001). Median NGAL was determined to be statistically significantly higher in the patient group (59.87ng/mL) compared with the control group (44.87ng/mL) (P = 0.013). In 23.6% of the patients without renal involvement at admission renal involvement developed within the following 6 months. When median KIM-1 and NGAL at admission of these patients were compared with the control group, they were determined to be statistically significantly higher (P = 0.001, P = 0.003). The fact that our patients with late-term nephropathy had no hematuria and / or proteinuria and that KIM-1 and NGAL levels were determined to be high indicates that these biomarkers might be potentially reliable, noninvasive and early determinants of kidney injury.

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.

Serum Neutrophil Gelatinase-associated Lipocalin: A Biomarker of Renal Impairment in Hypertensive Patients

Background and Aim: Hypertension is one of the leading causes of chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL) is a novel and sensitive biomarker in acute and chronic renal injury. The present study investigated serum and urinary NGAL as markers of kidney damage in hypertensive and CKD patients. Materials and Methods: This case-control study was performed on 28 hypertensive patients, 28 patients with CKD, and 33 healthy volunteers. Serum and urinary NGAL levels were measured using the ELISA method. Creatinine and urea concentrations were measured by the routine methods. Receiver-operating characteristic (ROC) curve analysis was employed to find the best serum and urinary NGAL cut-off values for detecting renal function. Results: Both serum and urinary NGAL levels were higher in CKD patients than in hypertensive patients and healthy controls (serum NGAL: 193.48±50.62 vs 99.47±26.65 and 48.74±12.07, P&lt;0.001; urinary NGAL: 63.78±16.54 vs 23.24±6.87 and 11.36±3.4, P&lt;0.001 respectively). There was a significant positive correlation between serum and urinary NGAL with serum urea and creatinine. Serum and urinary NGAL levels showed a significant inverse correlation with the estimated glomerular filtration rate. In ROC analysis, serum NGAL had the best diagnostic profile with an AUC of 0.938 (95% CI: 0.865–0.978) and the best cut-off value of 64.61 ng/mL (sensitivity 97.73%; specificity 77.27%. Conclusion: These results revealed that serum NGAL is a reliable marker for early diagnosis of renal injury in hypertensive patients.

Urinary Neutrophil Gelatinase-associated Lipocalin: As an Early Marker for Diabetic Nephropathy

Background: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Diagnostic marker to detect diabetic nephropathy at early stage is important as early intervention can slow the loss of kidney function and reduce adverse outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) is a small (25-kd) protein that belongs to the lipocalin protein family. Urinary NGAL (u-NGAL) levels have been demonstrated to be a very promising marker especially in acute kidney disease. Objective: To measure urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker for diagnosis of diabetic nephropathy in type 2 diabetes mellitus (T2DM) patients. Patients and Methods: The study was conducted on 84 subjects, from (18- 80 years old), 45 (53.5%) were males and 39 (46.4%) were females, with mean age (58.18 ± 13.98). They were collected from Endocrinology and Nephrology Clinic after a written consent was taken from the patients at Zagazig University Hospital. Results: Urinary NGAL is higher in diabetic patients compared with non-diabetic controls with high significant difference (p < 0.0001). In our result we found a positive correlation between NGAL and the duration of DM (r =0.279, p=0.027). There was a positive correlation between NGAL level and HbA1C, with significant difference (r =0.778, p =0.000) in patients groups. Our results showed a positive correlation between NGAL and FPG (r= 0.562) (p < 0.001) and 2hPPPG (r=0.687) (p < 0.001). There was a positive correlation between NGAL level and albumin-creatinine ratio (Alb/Cr) with significant difference (r =0.888, p < 0.001) in patients groups. Conclusion: There was a high significant difference in the level of urinary NGAL in diabetic patients than control subjects. Urine NGAL had a positive correlation with albumin-creatinine ratio, duration of DM, HbA1c.

Time dependant functional and morphological recovery of the kidney after relief of obstruction in patients with impacted ureteral stones.

To assess the course of functional and morphological recovery of the kidney following the relief of obstruction with ureteral JJ stent in cases with unilateral impacted stones. A total of 42 adult patients who were admitted to our clinic with unilateral obstructing impacted ureteral stones requiring JJ stent placement were included in the study. The course of functional recovery was assessed by evaluating the serum creatinine levels, renal resistive index (RRI) values and urinary levels of kidney injury molecule-1, neutrophil gelatinaseassociated lipocalin as well as microalbumin before at 1 day, 1 week and 4 weeks after JJ stent placement. Course of morphologic recovery was evaluated by evaluating the degree of hydronephrosis, kidney size, perirenal straining and ureteral diameter. Our results showed that all relevant parameters began to decrease after 24 hours and continue to normalize during 1 week evaluation; majority of these variables indicating the functional and morphological recovery were in normal range after 4 weeks. Decompression of the obstructed kidneys with JJ stent placement in patients with impacted ureteral stones was found to be effective enough with recovery of normal renal functional and morphological status after a minimum time period of 4 weeks. Morphological recovery of affected kidneys following JJ stenting was obtained with a significant difference between baseline and 1-month evaluation findings (p = 0.001, p < 001, p < 001, respectively). KIM-1 excretion began to decline to normal levels after 4 weeks (3.52 ± 0.99 ng/ml versus 2.84 ± 0.66 ng/ml, p < 0.001). The same findings were observed for the urinary excretion levels of NGAL, which normalized at the 1-month evaluation (604.55 ± 140.28 ng/ml versus 596.87 ± 80.17 ng/ml p = 0.895). Urinary microalbumin excretion levels however remained high even until 1-month follow-up with a statistically significant difference when compared with the normal excretion values (p < 0.001). There was a statistically significant difference in RRI values between baseline and 1-month follow-up findings in obstructed kidney (p < 0.001). Elective management of the obstructing impacted ureteral stone(s) will be safer with limited risk of infective complications after functional and morphological normalization in such kidneys following 4 weeks of JJ stent placement.

Balanced Salt Solution Versus Normal Saline in Resuscitation of Pediatric Sepsis: A Randomized, Controlled Trial.

Current evidences in resuscitation of adult sepsis have pointed to the importance of types of crystalloid fluid-related complications on resuscitation outcomes, but evidences are lacking in pediatric populations. In this study, the authors aimed to compare outcomes of pediatric sepsis resuscitation with different types of crystalloid. They randomly assigned pediatric sepsis patients requiring fluid bolus into three groups to receive either normal saline solution (NSS), Ringer lactate solution (RLS), or Sterofundin as fluid bolus therapy. Forty-two patients were included in the study. Median age was 29 mo and, weight 13 kg. After fluid bolus, the complications were not different among groups. However, in the RLS group, the patients who received large dose of the fluid showed significant reduction in urinary neutrophil gelatinase-associated lipocalin (uNGAL) level. It is concluded that fluid bolus therapy with different types of crystalloid solution did not result in different outcomes but large dose of RLS was associated with greater reduction of uNGAL level, compared to other fluids.Trial Registration: Thai Clinical Trial Registry (TCTR) identification number TCTR20170605001 (retrospectively registered on 1st June 2017). https://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task20=search&task2=view1&id=2576

Urine neutrophil gelatinase-associated lipocalin (NGAL) measurement is not predictive for ureteral patency in pediatric patients following pyeloplasty: a pilot study

Objective: To evaluate the benefit of urine neutrophil gelatinase-associated lipocalin (NGAL) measurement to predict the ureteral patency in pediatric patients undergoing pyeloplasty. Materials and Methods: Ureteropelvic junction obstruction patients who underwent unilateral dismembered pyeloplasty had urine NGAL measurements taken intraoperatively during pyeloplasty and postoperatively at six months following surgery. All patients were evaluated preoperatively and postoperatively with renal scans. Pairwise comparisons and correlation analyses were performed to determine the dynamics and benefits of urine NGAL measurement. Results: Thirteen patients were included in this pilot study with a mean age of 3.2 years at surgery. Mean intraoperative bladder urine level was 4.43 ng/mL, and median intraoperative renal pelvic urine NGAL level was 3.70 ng/mL. There was no significant difference between these two levels (p-value = 0.76). Six months after pyeloplasty, 9/13 patients demonstrated significant reduction in the bladder urine NGAL level (at least 50% reduction), and 5/13 patients showed ureteral patency based on postoperative renal scan (more than 5% improvement in differential renal function or the conversion of diuretic half time. However, the finding of significant reduction of urine NGAL level did not correlate with ureteral patency (r = -0.50, p-value = 0.08). Conclusion: Although bladder urine NGAL level reduces in most pediatric patients following pyeloplasty, this decline is not reflective of the finding of ureteral patency from renal scanning. The benefits of urine NGAL measurement in this context remain unclear and require further large-scale investigation.

The influence of hyperbilirubinemia on indexes of kidney function in neonates.

To study the influence of hyperbilirubinemia on indexes of neonatal kidney function. A prospective cohort study was conducted September 2019 to March 2020 in Neonatology Department of Xuzhou Central Hospital. Neonates with gestational age ≥ 35 weeks and aged ≤ 7 days were included and divided into mild, moderate, and severe groups according to total serum bilirubin level. Epidemiologic and demographic data and daily urine output were recorded. Total serum bilirubin, serum creatinine, serum cystatin C, serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, and kidney injury molecule-1 were tested before and 12~18 h after phototherapy. Parameters of kidney function were compared between groups. Fifty-three, 52, and 49 neonates were included in the mild, moderate, and severe groups, respectively. Urine NGAL was higher in severe (1.36 ± 0.24 μg/L) compared to moderate (1.22 ± 0.19 μg/L) and mild groups (1.16 ± 0.19 μg/L), and differences were statistically significant (P = 0.004 and < 0.001, respectively). Urine NGAL was not significantly different between moderate and mild groups (P > 0.05). No significant differences in other kidney function indexes were observed between the three groups (all P > 0.05). Significant reduction in urine NGAL levels 12~18 h after stopping phototherapy was found in severe group ((1.17 ± 0.28) μg/L vs. (1.35 ± 0.23) μg/L, P < 0.001). Urine NGAL positively correlated with total serum bilirubin (r = 0.575, P < 0.001). Among all cases, neither serum creatinine nor daily urine output met neonatal acute kidney injury diagnostic criteria. Severe hyperbilirubinemia may temporarily impair renal tubular reabsorption functions in full-term and near-term neonates, which is likely reversible. However, it has little effect on glomerular filtration function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Are Tubular Injury Markers NGAL and KIM-1 Useful in Pediatric Neurogenic Bladder?

The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.

Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus.

Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7–18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.

Evaluation of Measurement of Urinary Neutrophil Gelatinase Associated Lipocalin for Diagnosis of Vesicoureteral Reflux in Children

Background: One of the most common urological disorders in childhood is vesicoureteral reflux (VUR) that can lead to kidney injury, scarring and chronic kidney disease. VUR is diagnosed by radiological methods, which are often invasive. We evaluated the possibility of diagnosing VUR by measuring urinary NGAL (Neutrophil gelatinase-associated lipocalin) in this study. Materials and Methods: This prospective cohort study was done on children aged 1-5 years old with recurrent urinary tract infections in 2017- 2018 in Sannandaj, Iran. After ruling out other causes of recurrent urinary tract infections, urinary levels of NGAL and creatinine (Cr) were measured in random urine simultaneously with voiding cystourethrography (VCUG). Then the patients were divided into 2 groups with and without VUR based on VCUG and the collected data were statistically analyzed in 2 groups. Results: In this study, 71 children (12-60 months) with a mean age of 23±36.35 months were studied, of which 34 children had VUR and 37 children did not have VUR. The mean urinary NGAL/Cr ratio in the group with VUR (3.45 ± 3.8 ng/mg) was significantly higher than the group without VUR (1.18± 0.8 ng/mg) (P: 0.002). The best cut-off point for urinary NGAL/Cr ratio was 1.27 ng/mg, with a sensitivity of 76.5% and specificity of 73% (ROC area: 0.76, P <0.001). Conclusion: Urinary NGAL/Cr ratio is higher in children with VUR and may be used as a rapid and non-invasive method in the diagnosis of VUR.

Renal effect of severe hypoxia evaluated By NGAL measurements: An in vivo and in vitro study.

To investigate possible renal damage in healthy men exposed to extreme hypobaric hypoxia, using urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentration as biomarker. The value of NGAL as a biomarker of proximal tubular cell damage under hypoxic conditions was also tested in vitro experiments. NGAL was assayed in a cohort of air cadets (n = 16) exposed to hypobaric hypoxia in a hypobaric chamber during their training program. In all subjects, urine creatinine (Cr) and urinary NGAL levels were measured immediately before, 3, and 24 h after hypobaric environment exposure. Three in vitro experiments using proximal tubular cell cultures were also performed to measure NGAL gene expression, NGAL secretion in the culture medium and to evaluate apoptosis under two cycles of hypoxia and reoxygenation. In the in vivo study, geometric means of urinary NGAL/Cr ratio measured 24 h after hypobaric hypoxia in the hypobaric chamber were significantly lower than baseline values (13.4 vs 25.9 ng/mg, p = 0.01). In cell cultures, hypoxia down-regulated NGAL gene expression without significantly changing NGAL secretion in the culture medium. Hypoxia significantly increased the percentage of apoptotic/necrotic cells, especially after the second hypoxia-reoxygenation cycle. Exposure to hypobaric-hypoxic environments does not cause significant and irreversible renal tubular injury in vivo and in vitro, except than in a late stage. The hypoxic insult does not seem to be mirrored by an increase of urinary NGAL in healthy men nor of NGAL gene expression in HK-2 cell culture or secretion in the culture medium in the in vitro conditions reported in the present study.

Isorhynchophylline ameliorates paraquat-induced acute kidney injury by attenuating oxidative stress and mitochondrial damage via regulating toll-interacting expression

Isorhynchophylline (IRN) is an alkaloid with anti-inflammatory and anti-oxidative activities in cardiovascular and brain diseases, but its role in paraquat (PQ)-induced acute kidney injury (AKI) is yet unknown. The model of PQ-induced AKI in rats was established by intraperitoneal injection of PQ (25 mg/kg). We found that the tail vein injection of IRN (4 mg/kg) significantly increased the survival rate of PQ-intoxicated rats. IRN administration alleviated PQ-induced renal injury and renal dysfunction in rats, as evidenced by decreased apoptosis in renal cortex and reduced serum creatinine, serum BUN, and urine NGAL levels. Furthermore, IRN treatment improved the PQ-triggered oxidative stress in renal cortex by increasing the levels of anti-oxidant indicators (SOD activity, GSH/GSSG ratio, levels of Nrf-2, NQO-1, and HO-1 in renal cortex) and decreasing the levels of oxidative stress indexes (ROS and MDA levels in renal cortex). Interestingly, toll-interacting protein (Tollip), a negative regulator of interleukin 1 receptor associated kinase 1 (IRAK1) phosphorylation, was demonstrated to be increased by IRN injection in the renal cortex of PQ-intoxicated rats. In vitro experiments revealed that IRN protected renal tubular epithelial cells against PQ toxicity through suppressing oxidative stress and mitochondrial damage, and these protective effects were reversed by Tollip shRNA. Collectively, the present study demonstrated that IRN ameliorated PQ-induced AKI by attenuating oxidative stress and mitochondrial damage through upregulating Tollip, which provides new insights into the pathogenesis and treatment of PQ poisoning.

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

BackgroundThe 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.MethodsForty 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.ResultsThere 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).ConclusionsDetection 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.

Occupational Paraquat and Glyphosate Exposure May Decline Renal Functions among Rural Farming Communities in Sri Lanka

Extensive use of herbicides is common among rural agricultural workers in Sri Lanka. Recent studies have postulated their role in the development of chronic kidney disease of unknown etiology (CKDu). Paraquat and glyphosate are leading herbicides used by sugarcane farmers (SF), hence occupational exposure is inevitable. This study examined the expression of urinary paraquat, glyphosate and biomarkers among residential SF in CKDu emerging regions, Warunagama (WA) and Rahathangama (RH), in the Uva Province with non-endemic Matara (MA) in the Southern Province of Sri Lanka. Urinary glyphosate, Paraquat, kidney injury molecule -1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and β2-microglobulin (B2M) were determined using enzyme-linked immunosorbent assays (ELISA). Urinary creatinine, microalbumin, serum creatinine (SCr), serum cystatin C, estimated glomerular filtration rate (eGFR), and albumin creatinine ratio (ACR) were also assessed. Generally, herbicide residues and kidney injury biomarkers were higher in SF compared to the non-endemic MA. Creatinine-adjusted urinary glyphosate and paraquat levels were significantly higher in WA compared to MA. ACR in RH (median 14.9; IQR 5.4–393.1 mg/g) and WA (23.7; 11.5–64.6) was significantly higher than MA (4.3; 2.2–6.7). This study reports 39 individuals with impaired kidney function among SF in Sri Lanka for the first time. Urinary NGAL levels were significantly higher in both WA (median 2.14; IQR 1.28–6.15 ng/mg Cr) and RH (3.09; 1.15–9.09) compared to MA (1.28; 0.56–2.81). However, urinary KIM-1 levels in RH (3.2; 1.29–106.1 ng/g Cr) and WA (3.6; 1.94–115.1) were not significantly higher in MA (1.74; 0.76–116.9). Urinary NGAL (r = 0.493), eGFR (r = −0.147) and ACR (r = 0.171) significantly correlated with urinary glyphosate, but not with urinary paraquat levels. Urinary KIM-1 levels did not correlate with either urinary glyphosate or paraquat, while urinary B2M and serum cystatin C levels showed significant correlation with urinary glyphosate levels. The current study reports higher urinary herbicide levels among sugarcane farmers in WA and RH, and that is potentially linked to the subsequent decline in kidney function, as indicated by ACR, eGFR, and NGAL. We posit that these indicators may serve as markers to detect renal injury among herbicide-exposed SF in Rural Sri Lanka.

Neutrophil Gelatinase-Associated Lipocalin (NGAL): An Early Dual Biomarker in Diagnosis of Ascitic Fluid Infection and Acute Kidney Injury in Liver Cirrhosis in a Tertiary Centre, Egypt

Background: This study aimed to evaluate the ascitic Neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic biomarker for bacterial translocation or bactDNA translocation in ascites of cirrhotic patients and to evaluate the urinary NGAL for identifying renal dysfunction in patients with liver cirrhosis.&#x0D; Methods: This study included 44 patients with ascites. Study participants were divided into two groups. Group (1) had 22 patients with neutrocytic ascites and/or positive ascitic fluid (AF) culture while group (2) included 22 patients with culture negative non neutrocytic ascites (CNNNA), recruited as controls. AF and urine samples were collected from all studied participants. ELISA kit was used for measurement of NGAL levels in AF and urine. DNA extraction and PCR were done.&#x0D; Results: Values of NGAL in ascitic fluid were statistically significantly higher in bactDNA positive group. At cutoff 143.9 ng/ml, ascites NGAL had 86.4% sensitivity, 45.5% specificity, 61.3% positive predictive value (PPV) and 76.9% negative predictive value (NPV). When comparing ascites NGAL between bactDNA positive and negative group, NGAL has a sensitivity of 86.2% and a specificity of 46.7%, PPV of 75.8%, NPV of 63.6%. As for urine NGAL, patients with AKI had statistically significant higher levels of NGAL. Urine NGAL achieved sensitivity of 77.3%, specificity of 50%, PPV of 60.7%, NPV of 68.75%.&#x0D; Conclusion: Early and accurate diagnosis of BT or bactDNA translocation can be aided by utilizing NGAL especially in ruling out infection in those reported to have negative culture results, besides, it can help in early detection of complication of cirrhosis and infection especially AKI helping in the improving the prognosis of cirrhotic patients. It is an advantage that a single marker can detect both infection and kidney injury.