Value Of Urinary Neutrophil Gelatinase-associated Lipocalin Research Articles

Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon.

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P < 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P < 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p < 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P < 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P < 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P < 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation.

Assessment of the diagnostic ability of RIFLE classification and neutrophil gelatinase-associated lipocalin biomarker in detecting acute kidney injury in newborns at the intensive care unit

Introduction/Objective. This study was designed to demonstrate the association of the RIFLE classification and neutrophil gelatinase-associated lipocalin (NGAL) in predicting of newborns with acute kidney injury (AKI). Methods. This was a prospective study. We included 100 newborns suspected of having a kidney injury. These newborns were admitted to the intensive care unit (ICU) at the University Clinic of Pediatrics from the period of two years. The severity of the disease was determined by RIFLE classification. The biochemical marker NGAL was included in this study because it is an early biomarker of AKI in newborns. The statistical processing of the material was by methods of descriptive statistics. Results. The prevalence rate of AKI was 6.25%, but according to the RIFLE classification the prevalence was 8.7%. According to RIFLE classification, we reported ?risk? in 36%, ?injury? in 50% and ?failure? in 14% of newborns with AKI. In newborns with perinatal asphyxia, kidney injury was seen in 34% and 30%, making perinatal asphyxia the most common predisposing factor. The difference in average value of the score for neonatal acute physiology with perinatal extension in newborns with AKI and the control group without AKI was confirmed significant (p &lt; 0.001). Also, there was a significant difference (p &lt; 0.001) between serum creatinine and urinary NGAL values, on the day they were admitted to the ICU. Conclusion. In newborns hospitalized in the ICU, AKI is a serious condition. We could identify kidney injury and follow up the progression of the disease by using RIFLE classification. The need for early diagnosis of kidney injury, in a period when the disease is not clinically manifest, in the first hours of its occurrence, is provided by NGAL.

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.

Investigation of new biomarkers of kidney injury in renal transplant recipients undergoing graft biopsy.

Urinary and blood kidney biomarkers (BM) remain insufficient for early kidney injury detection. We aimed to compare new kidney BM with histopathological data in kidney allograft recipients. Blood and urine samples were collected from consecutive adult patients just before graft biopsy. All kidney samples were classified according to the Banff 2007 classification. The diagnostic performance of 16 new BM was compared to those of urinary proteins, blood urea nitrogen, eGFR, and serum creatinine to identify histopathological groups. Two hundred and twenty-three patients were analyzed. Microalbuminuria and urinary proteins performed well to discriminate glomerular injury from slightly modified renal parenchyma (SMRP). Urinary neutrophil gelatinase-associated lipocalin (NGAL) had the best performance relative to SMRP (AUROC .93) for acute tubular necrosis (ATN) diagnosis. Other BM had a slightly lower AUROC (.89). For the comparison of ATN to acute rejection, several new urinary BM (NGAL, cystatin C, MCP1) and classical BM (eGFR, serum creatinine) gave similar AUROC values (from .80 to .85). Urinary NGAL values in patients with ATN were 10-time higher than those with acute rejection (P=.0004). The new BM did not outperform classical BM in the context of renal transplantation. Urinary NGAL may be useful for distinguishing between ATN and acute rejection.

Post-Operative Fluid Overload Is Associated with AKI and Elevated Urinary Neutrophil Gelatinase-Associated Lipocalin Values

Post-Operative Fluid Overload Is Associated with AKI and Elevated Urinary Neutrophil Gelatinase-Associated Lipocalin Values

The value of urinary NGAL compared to serum creatinine level in predicting acute kidney injury among neonates

Background: The diagnosis of acute kidney injury (AKI) is focused on the measurement of glomerular filtration rate based on serum creatinine; nevertheless, due to the effects of the underlying confounding parameters, this procedure tends to have some problems. Recent findings identified neutrophil gelatinase-associated lipocalin (NGAL) to be a critical marker for predicting AKI in humans. The aim of the present study was to evaluate changes in urinary NGAL levels in neonates with AKI and those without AKI.Methods: This cross-sectional analytical study was conducted on a total of 75 neonates hospitalized for AKI and 81 neonates hospitalized for reasons not related to kidney disease. The serum concentrations of NGAL creatinine and urine were measured in both groups.Results: The mean NGAL levels were 825.81±175.08 and 292.20±322.03 ng/ml in the case and control groups with a substantial difference, respectively. The NGAL had a sensitivity of 100%, specificity of 55.6%, positive predictive value of 67.6%, negative predictive value of 100%, and accuracy of 76.9% in predicting AKI. Assessing the region under the receiver operating characteristic curve (ROC curve) showed that measurement by NGAL effectively discriminated AKI from normal conditions (area under the ROC curve=0.899). The NGAL’s best cut-off value for predicting AKI among neonates was estimated at 427 ng/ml, resulting in a sensitivity of 100% and specificity of 67.9%. Using Pearson’s correlation coefficient test revealed a strong linear connection between the NGAL level and altered creatinine level (r=0.395; p <0.001).Conclusion: The measurement of urinary NGAL in predicting AKI among neonates has high sensitivity and proper specificity, compared to that reported for the creatinine level.

The assessment value of urinary NGAL combined with blood NLR in the early prognosis of patients with acute paraquat poisoning

Objective: To explore the evaluate of neutrophil gelatinase-associated lipocalin (NGAL) , combined with neutrophil/lymphocyte ratio (NLR) in the early prognosis of patients with acute paraquat poisoning (APP) . Methods: In March 2019, 108 APP patients admitted to Emergency Medicine Department of Hebei Medical University from January 2017 to December 2018 were selected as the observation group, 60 healthy people in the same period were see as the control group according to the results of diagnosis and 28-day survival, the observation group was divided into 51 death group and 57 survival group. The correlation between NGAL, NLR and the death of APP patients was analyzed, to explore the value of NGAL and NLR in predicting the death of APP patients. Results: Compared with the Control group, the NGAL and NLR in the observation group were significantly higher (P<0.01) , and the NGAL and NLR in the death group were significantly higher (P<0.05) . The results showed that NGAL and NLR were positively correlated with the death of APP patients on 28th day, and the Correlation Coefficient was 0.456 and 0.638 at 2nd Day (P<0.01) The area under the ROC curve of NGAL, NLR and their combination were 0.764, 0.869 and 0.905, respectively. Conclusion: The combined detection of NGAL and NLR has important clinical significance in the early prediction of 28-day mortality in APP patients.

The Application of Urinary NGAL Measurement for Early Detection of AKI in Hospitalized Patients with Poisoning.

Introduction Early diagnosis of acute kidney injury is critical for decision-making. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker introduced for early detection of acute kidney injury (AKI). We evaluated urinary NGAL level in hospitalized patients due to poisoning as a predictor of AKI. Methods We studied patients with poisoning due to various causes. Urinary NGAL and urine creatinine levels were measured. Serum creatinine levels were measured for all patients at baseline and after 24 and 48 hours. Then, a ROC curve developed for urinary NGAL, and cutoff point and accuracy of urinary NGAL test were determined. Results Ninety hospitalized patients with acute poisoning were consecutively recruited into the study over an eight-months period. With the gold standard test (i.e., serum creatinine measurement), 21 patients were diagnosed with acute kidney injury (AKI) and 69 with non-AKI, whereas according to ROC curve, at a cutoff point of 110 ng/ml, urinary NGAL with an 81% sensitivity and 91.3% specificity distinguished 23 patients with AKI and 67 with non- AKI. The false positive and false negative values of urinary NGAL test were 8.7% and 19%, respectively. The positive predictive value and negative predictive value of urinary NGAL were estimated to be 73.9% and 94%, respectively. Conclusion Urinary NGAL test, with an AUC of ROC curve of approximately 90% and a sensitivity of 81%, can be used for early detection of AKI. It has a high specificity (91.3%), indicating that the percentage of false positive cases (8.7%) will be small.

Neutrophil Gelatinase-associated Lipocalin as a Marker of Postoperative Acute Kidney Injury Following Cardiac Surgery in Patients with Preoperative Kidney Impairment.

Acute kidney injury (AKI) is a serious complication of cardiac surgery. The current 'gold standard' for determining AKI is change in serum creatinine and urine output, however, this change occurs relatively late after the actual injury occurs. Identification of new biomarkers that detect early AKI is required. Recently, new biomarkers, such as the NephroCheck® Test and AKIRisk have also been tested and found to be good indicators of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in paediatric patients but has displayed varied results in adult populations, particularly post cardiac surgery. The aim of this study was to assess the value of urinary NGAL as a biomarker of AKI in patients with pre-existing renal impairment (eGFR >15ml/min to eGFR<60ml/min). A post-hoc analysis of urinary NGAL concentrations from 125 patients with pre-existing kidney impairment, who participated in a randomised trial of haemofiltration during cardiac surgery, was undertaken. Urinary NGAL was measured using ELISA at baseline, post-operatively and 24 and 48 hours after surgery, and serum creatinine was measured pre and postoperatively and then at 24, 48, 72 and 96 hours as routine patient care. NGAL concentrations were compared in patients with and without AKI determined by changes in serum creatinine concentrations. A Kaplan-Meier plot compared survival for patients with or without AKI and a Cox proportional hazards analysis was performed to identify factors with the greatest influence on survival. Following surgery, 43% of patients developed AKI (based on KDIGO definition). Baseline urinary NGAL was not found to be significantly different between patients that did and did not develop AKI. Urinary NGAL concentration was increased in all patients following surgery, regardless of whether they developed AKI and was also significant between groups at 24 (p=0.003) and 48 hours (p<0.0001). Urinary NGAL concentrations at 48 hours correlated with serum creatinine concentrations at 48 hours (r=0.477, p<0.0001), 72 hours (r=0.488, p<0.0001) and 96 hours (r=0.463, p<0.0001). Urinary NGAL at 48 hours after surgery strongly predicted AKI (AUC=0.76; P=0.0001). A Kaplan- Meier plot showed that patients with postoperative AKI had a significantly lower 7-year survival compared with those without AKI. Postoperative urinary NGAL at 48 hours >156ng/mL also strongly predicted 7-year survival. However, additive EuroSCORE, age, current smoking and post-operative antibiotics usage were distinctly significantly more predictive of 7-year survival as compared with postoperative urinary NGAL at 48 hours >156ng/mL. Our study demonstrated that postoperative urinary NGAL levels at 48 hours postsurgery strongly predicts the onset or severity of postoperative AKI based on KDIGO classification in patients with preoperative kidney impairment and were also strongly related to 7-year survival.

Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis

The neutrophil gelatinase-associated lipocalin (NGAL) has been emerging as a novel biomarker of acute kidney injury while its value in lupus nephritis is uncertain. The aim of this study was to assess urinary NGAL levels as a marker for disease activity in patients with lupus nephritis.This study included 70 systemic lupus erythematosus (SLE) patients; 50 with active lupus nephritis (LN) and 20 without as well as 20 matched controls. The neutrophil gelatinase-associated lipocalin (NGAL) in both serum and urine samples was measured by enzyme-linked immunosorbent assay (ELISA). Patients with active LN received standard treatment then assessed for response as well as the value of urinary NGAL (uNGAL). Our results revealed that, The SLE patients with or without LN had an elevated urinary NGAL as compared to controls (p < 0.000) and the mean of uNGAL was (20.67 ± 5.34),(10.63 ± 3.53),(5.65 ± 2.49) respectively. Furthermore,Urinary NGAL levels in LN patients were significantly higher than those in non-LN patients (P < 0.0001). In the ROC curve analysis , the diagnostic performance of uNGAL for discriminating patients with nephritis from those without nephritis showed that the best cutoff value was 13.66 ng/ml ,sensitivity 92%,specificity 75%,area undercurve (0.959) and (P < 0.0001). Measurement of urinary NGAL levels showed an excellent diagnostic performance for discriminating patients with LN from SLE without nephritis.

Neutrophil gelatinase-associated lipocalin reflects inflammation and is not a reliable renal biomarker in neonates and infants after cardiopulmonary bypass: a prospective case-control study.

We prospectively enrolled 59 neonates and infants undergoing cardiopulmonary bypass surgery for CHD and measured neutrophil gelatinase-associated lipocalin in plasma and urine and interleukin-6 in the plasma. Values were correlated with postoperative acute kidney injury according to the paediatric Renal-Injury-Failure-Loss-Endstage classification. Overall, 48% (28/59) of patients developed acute kidney injury. Of these, 50% (14/28) were classified as injury and 11% (3/28) received renal replacement therapy. Both plasma and urinary neutrophil gelatinase-associated lipocalin values were not correlated with acute kidney injury occurrence. Plasma neutrophil gelatinase-associated lipocalin showed a strong correlation with interleukin-6. Urinary neutrophil gelatinase-associated lipocalin values correlated with cardiopulmonary bypass time. Our results suggest that plasma and urinary neutrophil gelatinase-associated lipocalin values are not reliable indicators of impending acute kidney injury in neonates and infants after cardiac surgery with cardiopulmonary bypass. Inflammation may have a major impact on plasma neutrophil gelatinase-associated lipocalin values in infant cardiac surgery. Urinary neutrophil gelatinase-associated lipocalin may add little prognostic value over cardiopulmonary bypass time.

Cystatin C, but not urinary or serum NGAL, may be associated with contrast induced nephropathy after percutaneous coronary invasive procedures: A single center experience on a limited number of patients.

This study aimed to test the association of both the baseline values and post-procedural variations of urinary and serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C (CysC) with contrast induced nephropathy (CIN) occurrence in patients undergoing percutaneous coronary invasive procedures (PCIP), and compare them to serum creatinine and the estimated glomerular filtration rate (eGFR). In 43 patients admitted to our Cardiac Step-Down Unit and submitted to PCIP, we measured serum creatinine and eGFR as the standard markers for CIN diagnosis, and compared them to both serum and urinary NGAL as well as serum CysC, assessed before and 4 hours after PCIP. Patients who developed CIN (16%) were older, with significantly higher discharge creatinine values, lower eGFR values at creatinine peak, and higher baseline and post-PCIP CysC values. We did not detect any significant association between baseline serum and urinary NGAL values and their 4 hour variations after contrast medium administration and CIN occurrence. Furthermore, we observed that the baseline values of both serum and urinary NGAL were significantly higher in patients with greater neutrophil count. In our population submitted to PCIP, neither baseline serum and urinary NGAL nor their variations after PCIP were related to CIN occurrence, while CysC results were associated with CIN development, earlier than creatinine and eGFR variations.

Comparison of urine neutrophil gelatinase-associated lipocalin to serum creatinine to assess kidney function in neonatal asphyxia

Background Infants with neonatal asphyxia have multiorgan damage, such as to the kidneys (50%), central nervous system (28%), cardiovascular system (25%), and lungs (23%). Neonatal asphyxia reduces kidney perfusion, often leading to acute kidney injury (AKI) after asphyxia. Neutrophil gelatinase-associated lipocalin (NGAL) levels in the blood, urine and kidney tissue increased rapidly in AKI. Urinary NGAL is proposed to have better performance in diagnosing AKI than creatinine due to its earlier, rapid level increase and it is less invasive.Objective To compare urinary NGAL to serum creatinine as a marker to assess kidney function in neonatal asphyxia.Methods Diagnostic comparison study with cross-sectional design was performed at neonatal intensive care unit (NICU) of Prof. Dr. R. D. Kandou Hospital, Manado from November 2015 to February 2016. All subjects had neonatal asphyxia. Data were analyzed using descriptive analysis, receiver-operator characteristic (ROC) curve, and Z-test.Results Urinary NGAL with cut-off point of 652.24 ng/mL can predict AKI in neonates with asphyxia with 100% sensitivity, 75% specificity, 52.3% positive predictive value, and 100% negative predictive value. Chi-square test resulted in a value of x2 = 20.036, P=0.0001).This shows that urinary NGAL levels &gt;652,24 ng/mL can predicts AKI by 20 times in infants with neonatal asphyxia. So, urinary NGAL performs better than serum creatinine, therefore it can replace serum creatinine as an alternative non-invasive diagnostic test for diagnosing AKI in infants with neonatal asphyxia.Conclusion The diagnostic value of urinary NGAL is higher than that of serum creatinine in assessing kidney function in neonatal asphyxia.

Is urinary neutrophil gelatinase-associated lipocalin able to predict acute kidney injury episodes in very low birth weight infants in clinical settings?

We evaluated the potential utility of elevated urinary neutrophil gelatinase-associated lipocalin (UNGAL) concentration as a screening test for early identification of acute kidney injury (AKI) in very low birth weight (VLBW) newborns. Urine for UNGAL analysis was collected prospectively daily until 32 wk postmenstrual age in 91 VLBW newborns, yielding 2,899 specimens. UNGAL values > 50 ng/ml were considered elevated. AKI was defined as two or more consecutive elevations in s[Cr] above the 95th percentile adjusted for gestational age and chronological age within a 48 h period. We compared UNGAL values taken during the 5 d prior to AKI onset (pre-AKI) to values taken during non-AKI days. Overall, 15 episodes of AKI were identified in 13 infants. UNGAL was available in 44 pre-AKI days and 969 non-AKI days. UNGAL > 50 ng/ml occurred more often in pre-AKI days than in non-AKI days (risk ratio 3.48 (1.89, 6.40)). Positive and negative likelihood ratios were 1.92 (1.52, 2.41) and 0.52 (0.34, 0.78), respectively. Although UNGAL elevation > 50 ng/ml discriminates between pre-AKI and non-AKI days, high false positive and false negative rates limit utility as a screening test in VLBW newborns.

STUDY OF URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) IN PATIENTS WITH LIVER CIRRHOSIS AND ITS RELATION TO HEPATORENAL SYNDROME

Background: Hepatorenal syndrome (HRS) is a unique form of kidney injury resulting from renal vasoconstriction in the setting of systemic and splanchnic arterial vasodilatation in patients with advanced cirrhosis. Neutrophil gelatinase-associated lipocalin (NGAL) is a proved biomarker of acute and chronic renal injury. Aim of the work was to study urinary NGAL level in patients with liver cirrhosis and its relation to HRS. Subjects and methods: The study included 5 groups; group I (15 patients with cirrhosis, no ascites and normal renal function), group II (15 patients with cirrhosis, ascites and normal renal function), group III (15 patients with cirrhosis, ascites and HRS), group IV (15 patients with cirrhosis, ascites and chronic kidney disease; CKD) and group V (15 healthy subjects) as control group. The diagnosis of HRS was based on the International Ascites Club criteria. The glomerular filtration rate (GFR) was calculated using 2 formulas: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Extended Modification of Diet in Renal Disease (Ext-MDRD) formula. Urinary level of neutrophil gelatinase lipocalin (NGAL) was done using ELISA, and neutrophil gelatinase associated lipocalin/ urinary creatinine concentration (NGAL/UCC) ratio was calculated. Results: Both NGAL level and NGAL/UCC ratio increased significantly in cirrhotic patient with HRS, while only NGAL/UCC ratio significantly increased in cirrhotics with CKD compared to normal controls and to cirrhotics with normal serum creatinine. NGAL level and NGAL/UCC ratio were higher in HRS compared to CKD cirrhotics, they could successfully identify HRS at cut-off values of 100 ng/ml and 0.9, respectively. Both markers correlated with each other and with blood urea, serum creatinine, estimated GFR, and Child-Pugh score of patients. Conclusion: Urinary NGAL level and NGAL/UCC ratio can be used as markers for early detection of HRS among patients with cirrhosis. However, the elevation of NGAL in the setting of HRS confirms the speculation that HRS entails a degree of structural kidney injury rather than being purely functional. Larger studies with higher number of patients are needed to investigate the value of urinary NGAL in type I and type II HRS separately, and to examine the role of other markers for early detection of HRS to improve its prognosis. Key Words: Hepatorenal syndrome: HRS, Neutrophil gelatinase-associated lipocalin: NGAL, chronic kidney disease: CKD, the Chronic Kidney Disease Epidemiology Collaboration: CKD-EPI, the Extended Modification of Diet in Renal Disease: Ext-MDRD, neutrophil gelatinase associated lipocalin/ urinary creatinine concentration: NGAL/UCC .

Urinary neutrophil gelatinase-associated lipocalin: potential biomarker for late-onset sepsis.

To assess the ability of urinary neutrophil gelatinase-associated lipocalin (UNGAL) to discriminate between culture-positive vs. culture-negative late-onset sepsis evaluations. This is a prospective observational study of 136 neonates who underwent ≥1 sepsis evaluation at >72 h of age. Urine was obtained at the time of sepsis evaluation to measure UNGAL concentration. Using generalized estimating equations controlling for gender, gestational and postnatal age, acute kidney injury, and within-patient correlations, pair-wise contrasts between mean log UNGAL concentrations of infants with negative sepsis evaluations vs. culture-positive sepsis and presumed sepsis were assessed. Discrimination characteristics at several UNGAL cutoff concentrations were assessed using receiver-operating characteristic curves. The predicted mean log UNGAL values of culture-positive sepsis and presumed sepsis vs. negative sepsis evaluations differed significantly (P < 0.001 and P = 0.02, respectively). At a cutoff ≥ 50 ng/ml, UNGAL discriminated between culture-positive sepsis and culture-negative sepsis evaluations with sensitivity = 86%, specificity = 56%, positive predictive value = 41%, negative predictive value = 92%, and number needed to treat = 3. UNGAL is a noninvasive biomarker with high negative predictive value at the time of late-onset sepsis evaluation in neonates and could be a useful adjunct to traditional components of sepsis evaluations.

High expression of neutrophil gelatinase-associated lipocalin (NGAL) in the kidney proximal tubules of diabetic rats

PurposeRecent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) plays important roles in many physiological and pathological processes including diabetic nephropathy (DN), in which a markedly increasing in NGAL levels in patient's serum and urine has been reported. This study investigated the expression of NGAL in the kidney of diabetic rats. Materials/methodsSixty-four Sprague Dawley rats were randomly divided into 2 groups: non-diabetic control groups and diabetic groups. Diabetes was induced by intraperitoneal injection of streptozotocin. Relevant indicators were separately evaluated 2, 4, 8 and 12 weeks after induction of diabetes. ResultsIn the diabetic groups, urinary NGAL values were markedly increased even before the appearance of pathological albuminuria. Moreover, diabetic rats showed significant upregulation of NGAL mRNA expression starting at week 2 (1.0±0.03 vs. 3.09±0.40, NGAL/β-actin, P<0.05), while the increase of NGAL protein expression appeared subsequently (0.58±0.03 vs. 0.65±0.01, NGAL/β-actin, P<0.05). At the end of week 12, kidney NGAL mRNA and protein levels were increased to 5.95-fold and 1.24-fold of the control groups, respectively. Observable ultrastructural alterations of renal tubules were not detected until week 4, while pathological changes gradually became apparent in the course of the study. Strong positive immunohistochemical staining of NGAL was visualized in the proximal tubular cells of diabetic rats at week 12. ConclusionsHigh expression of NGAL in the kidney is associated with diabetic kidney injury in STZ rats, suggesting NGAL may play a role in tubular injury of DN.

Urine Liver-Type Fatty Acid-Binding Protein Predicts Graft Outcome up to 2 Years After Kidney Transplantation

BackgroundSeveral new biomarkers for the detection of early tubular injury have been investigated in kidney transplant recipients. We recently identified day 2 urinary neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of slow graft function and adverse 1-year outcome. In the present study, we further investigated the value of urinary NGAL and liver-type fatty acid binding protein (L-FABP) for predicting long-term graft outcomes up to 2 years. MethodsThis study was a single-center, prospective observational study. Serial urinary NGAL and L-FABP levels at 0 hours, 2 days, and 6 days after kidney transplantation (KT) were measured, and the clinical data were assessed during the 2-year period after KT. ResultsDuring the 2-year follow-up period, 13 (18.8%), 5 (7.2%), and 4 (5.8%) patients were diagnosed with acute T-cell–mediated rejection, acute antibody-mediated rejection (AMR) and chronic AMR, respectively. In addition, 10 patients (14.3%) developed calcineurin inhibitor toxicity and 6 (8.7%) developed BK viremia. The mean estimated glomerular filtration rates (eGFR) at 1 and 2 years after KT were 65.1 ± 19.1 and 58.5 ± 22.6 mL/min/1.73 m2, respectively, When poor long-term graft function was defined as eGFR of less than 50 mL/min/1.73 m2 at 2 years, elderly donors, acute rejection, and high 0-hour urinary L-FABP levels were significant risk factors. Furthermore, in rejection-free patients, L-FABP was strongly associated with poor long-term graft function (P = .006). Multivariate logistic regression analysis showed that high 0-hour L-FABP (P = .015) and acute rejection (P = .006) were independent factors predicting poor long-term graft function. Receiver operating characteristic analysis showed that the area under the curve for urinary L-FABP was 0.692 (P = .036). ConclusionsOur results suggest that urinary L-FABP may be a useful predictor of adverse long-term outcomes in KT patients.

Serum and Urinary NGAL in Septic Newborns

Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a potentially new and highly specific/sensitive marker of acute kidney injury (AKI). The aim of this study was to assess the impact of inflammation on serum and urine NGAL in newborns that were treated due to infection. We determined serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe sepsis) admitted to the Intensive Care Unit in the first month of life, for three consecutive days during the course of treatment for infection. 29 neonates without infection served as the control group. Septic patients, in particular, severe sepsis patients, had increased serum and urinary NGAL levels in the three subsequent days of observation. Five septic patients who developed AKI had elevated serum and urinary NGAL values to a similar extent as septic neonates without AKI. A strong correlation was found between the concentration of serum and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum and urinary NGAL levels were also significantly associated with NTISS (neonatal therapeutic intervention scoring system) values. We conclude that increased serum and urinary NGAL values are not solely a marker of AKI, and more accurately reflect the severity of inflammatory status.

Assessment of kidney function in diabetic patients. Is there a role for new biomarkers NGAL, cystatin C and KIM-1?

Assessment of kidney injury early detection in diabetic patients has great importance for therapy and prognosis. The aim of this study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and kidney injury molecule-1 (KIM-1) could represent sensitive markers of kidney function/injury in patients with coronary heart disease and diabetes. The study comprised 121 consecutive patients with diabetes referred for coronary angiography due to coronary heart disease and a reference group consisting of 64 patients without diabetes. Cystatin C, serum and urinary NGAL values were significantly higher in diabetics than in non-diabetics. There was no significant difference in KIM-1 levels in both groups. Serum NGAL in diabetic group was associated with serum creatinine, fibrinogen, urinary NGAL, cystatin C and inversely related to kidney function assessed with 4 equations. After analysing levels of studied biomarkers in both groups, no significant difference in patients with estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73m² was found. The analysis of patients with eGFR over 60 ml/min/1.73m² showed significant differences in cystatin C and urinary NGAL levels. The area under the curve for serum NGAL, urinary NGAL and cystatin C was 0.60 (95% CI, 0.51 to 0.69), 0.59 (95% CI, 0.5 to 0.68), 0.62 (95% CI, 0.54 to 0.71), respectively, good cut-off values of studied biomarkers to detect diabetes were not found. NGAL, cystatin C and KIM-1 are not more useful than eGFR in the assessment of kidney function in diabetic patients with coronary heart disease.