Neutrophil Gelatinase-associated Lipocalin Concentrations Research Articles

Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.

Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects. The current research aimed at evaluating the GA effect on CP-related renal toxicity. In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue. CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect. Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

Influence of clinical and experimental intra-articular inflammation on neutrophil gelatinase-associated lipocalin concentrations in horses.

ObjectiveTo investigate neutrophil gelatinase‐associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation.Study designExperimental studies and retrospective clinical study.Sample populationSerum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra‐articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivacaine (n = 6, mild inflammation).MethodsAvailability of samples was based on approval from the local ethical committee and from the Danish Animal Experiments Inspectorate. Neutrophil gelatinase‐associated lipocalin was measured with a previously validated enzyme‐linked immunosorbent assay. Repeated‐measurements one‐ and two‐way analysis of variance and correlation analysis were used to analyze NGAL concentrations and white blood cell counts (WBC).ResultsAfter injection of LPS or lidocaine, SF NGAL concentrations increased 343‐ (P = .0035) and 60‐fold (P = .0038) relative to baseline, respectively. Serum NGAL also increased in both groups (P < .05) but to lower concentrations than in SF. Concentrations were higher after injection of lidocaine SF NGAL than after injection of mepivacaine (P < .05) at 6 and 12 hours. Synovial fluid concentrations of NGAL were higher in horses with septic arthritis than in the nonseptic group (P = .0070) and in healthy controls (P = .0071). Concentrations of NGAL correlated with WBC in SF (P < .0001, R 2 = 0.49) and in blood (P = .0051, R 2 = 0.27).ConclusionNeutrophil gelatinase‐associated lipocalin concentrations increased in SF in response to experimentally induced and naturally occurring joint inflammation. Synovial fluid NGAL concentration correlated with WBC and, thus, seems to reflect intensity of joint inflammation.Clinical significanceNeutrophil gelatinase‐associated lipocalin may prove to be a useful biomarker of joint inflammation and infection in horses.

Association of plasma and urine NGAL with acute kidney injury after elective colorectal surgery: A cohort study

BackgroundAcute kidney injury (AKI) is common in surgical patients. We aimed to investigate the validity of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in the detection of AKI and prediction of outcomes in patients undergoing major colorectal surgery. Materials and methodsThis was a pre-specified post-hoc analysis of a randomized controlled trial comparing oesophageal doppler and Lithium dilution cardiac output monitoring in high risk patients undergoing major colorectal surgery as part of an Enhanced Recovery After Surgery protocol in a tertiary care hospital. Plasma and urine samples for NGAL measurement were taken before surgery (T1), immediately after surgery (T2), and on postoperative day 1 (T3). AKI was defined according to the KDIGO criteria. ResultsA total of 89 patients were included of whom 12 (13.5%) developed AKI. Plasma NGAL significantly increased from T1 to T3 in both AKI (p < 0.001) and non-AKI (p = 0.048) patients, while urine NGAL did not change over time. There were no significant differences in plasma and urine NGAL in patients with and without AKI at all time points. Postoperative day 1 urine NGAL concentrations were significantly higher in non-survivors than survivors (41.2 versus 25 ng/mL, p = 0.026). One-year mortality was significantly higher in AKI patients with a raised urine NGAL compared to AKI patients without elevated urine NGAL levels. ConclusionsPlasma and urine NGAL poorly predicted AKI post-colorectal surgery. Non-survivors had higher urine NGAL results. More research is required to explore the association between NGAL and long-term outcomes.

Urine NGAL and KIM-1-Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study.

The deterioration of renal function after childhood solid tumors treatment is the result of using the intensive multimodal therapy. In recent years, urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL) have been introduced as potential promising biomarkers of early kidney damage. The aim of the present study was to determine whether anticancer treatment has any effect on the concentration of KIM-1 and NGAL and its association with renal impairment in survivors of childhood solid tumors. Sixty patients previously treated for solid tumors were involved in this study. The median time after end of treatment was 8.35 years. Urine KIM-1 and NGAL levels were measured using immunoenzymatic ELISA commercial kits. Higher levels of urine NGAL, KIM-1/cr. (creatinine), and NGAL/cr. ratios were found in comparison with healthy controls (p < 0.0001). Among all subjects, 23% were found to have decreased estimated glomerular filtration rate (eGFR). A strong correlation between KIM-1/cr. and a cumulative dose of ifosfamide was observed (r = 0.865, p < 0.05). In addition, a moderate correlation between NGAL/cr. and a cumulative dose of cisplatin was identified (r = 0.534, p < 0.05). The AUC for KIM-1/cr. was 0.52, whereas NGAL/cr. showed a diagnostic profile describing the AUC of 0.67. Univariable regression showed significant associations between NGAL/cr. ratio and subjects after unilateral nephrectomy (coeff. 63.8, p = 0.007), cumulative dose of cisplatin (coeff. 0.111, p = 0.033), and age at diagnosis (coeff. 3.75, p = 0.023). The multivariable model demonstrated only cumulative dose of cisplatin as an independent factor influence on NGAL/cr. ratio. The results of our study showed increased levels of urine KIM-1 and NGAL many years after completion of the childhood solid tumors treatment, which correlated positively with a cumulative dose of ifosfamide and cisplatin. This study also suggests that unilateral nephrectomy could affect the concentration of the studied biomarkers.

Neutrophil gelatinase-associated lipocalin as a biomarker for predicting acute kidney injury after coronary artery bypass grafting

BackgroundEarly and precocious determination of acute kidney injury (AKI) is essential to prevent morbidity and mortality following coronary artery bypass grafting (CABG). Evaluation of the perioperative renal function is substantial using novel biomarkers other than the late traditional method of using serum creatinine. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker investigated for early detection of AKI in patients undergoing coronary artery bypass grafting, and its role has to be determined in this study.ResultsTwenty-five patients undergoing elective CABG were enrolled in this cohort study and were assigned into two groups: group I include the patients that did not develop AKI (no AKI group) and group II include the patients that developed AKI (AKI group). Acute kidney injury based on Kidney Disease: Improving Global Outcomes (KDIGO) classification had been developed in 7 patients (28%). Plasma NGAL levels at 6 h were higher in patients who developed AKI compared with those who did not (302 ± 88.02 vs. 116.50 ± 17.33 ng/m, p value < 0.001). The cut-off value of plasma NGAL levels measured 6 h postoperatively was 145 ng/ml and the area under the receiver-operating characteristic (ROC) curve was 0.965. Results of this study showed that plasma NGAL is a robust early biomarker of AKI, which preceded the rise in serum creatinine by many hours.ConclusionThis study revealed that earlier diagnosis of acute kidney injury in patients undergoing CABG can be achieved by measuring postoperative plasma NGAL concentration at 6 h.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) Measured at Admission is Associated With Development of Late Cardiogenic Shock and Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

In patients with ST-elevation myocardial infarction (STEMI) the immune system is activated with an inflammatory response to follow. In STEMI patients with a severe inflammatory response, risk of development of cardiogenic shock (CS) seems increased. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a glycoprotein released from mature neutrophils and plasma concentration may increase immediately after STEMI. We therefore aimed to assess whether admission NGAL plasma concentration in patients with STEMI was associated with CS development after leaving the catheterization laboratory (late CS) and 30-day all-cause mortality. From 1,892 consecutive patients with STEMI 1,626 (86%) had plasma NGAL concentration measured upon hospital admission before angiography throughout a 1-year period at two tertiary heart centers in Denmark. Patients were stratified according to NGAL quartiles (Q1-4). To assess late CS development, we adjusted for the Observatoire Régional Breton sur l'Infarctus risk score for late CS. For mortality assessment, we adjusted for gender, age, post-PCI culprit Thrombolysis in myocardial infarction flow, left ventricular ejection fraction (LVEF), kidney dysfunction, and being comatose after cardiac arrest. Increasing NGAL concentration was associated with higher age, more comorbidities, and more critical patient conditions including lower blood pressure and LVEF. When adjusted for factors associated with poor outcome, NGAL remained independently associated with both late CS development (Q4 vs. Q1-3) (OR (95% CI) 3.64 (1.79-7.41) and 30-day mortality (HR (95% CI) 3.18 (1.73-5.84)). Admission plasma concentration of NGAL in STEMI patients is independently associated with 30-day all-cause mortality and predictive of late CS development.

Urinary biomarkers as point-of-care tests for predicting progressive deterioration of kidney function in congenital anomalies of kidney and urinary tract: trefoil family factors (TFFs) as theemerging biomarkers.

Children with congenital anomalies of kidney and urinary tract (CAKUT) are at high risk of progressive deterioration of kidney function and further developing stage5 chronic kidney disease (CKD5), even after a successful surgery. This prospective study was designed to determine whether urinary biomarkers can predict progressive deterioration of kidney function in children with CAKUT. The study included 50 consecutive children, aged < 14 years, who were diagnosed with congenital uropathies (PUV, VUR, and PUJO) and 20 age-matched controls. Examination of four urinary biomarkers, i.e., trefoil family factors (TFF) 1 and 3, neutrophil gelatinase-associated lipocalin (NGAL) and microalbuminuria (MALB) was done at the beginning of follow-up. Kidney function was assessed, at the beginning and after 12-months of follow-up, by technetium-99m diethylene triamine pentaacetic acid (DTPA) and technetium-99m dimercaptosuccinic acid (DMSA) scans. Progressive deterioration in the kidney function was defined as a fall in the GFR from ≥ 60 to < 60 ml/min/1.73 m2 on comparing the baseline and latest DTPA scans; and/or new-onset cortical scar/scars or increase in the size of previous scar/scars on serial DMSA scans. Group 1 and group 2 included children without and with progressive functional deterioration respectively. The median (IQR) age of children with CAKUT and controls was 3 (1.5-5) and 2.3 (1.2-3.6) years, respectively, and showed no significant difference (p = 0.29). Median concentrations of TFF1, TFF3, NGAL, and microalbumin in patients were 44.5, 176.5, 281.2, and 15.5 mcg/gCr, respectively, and were significantly elevated as compared to controls (p < 0.05). Children belonging to group 2 had significantly higher concentration of biomarkers as compared to those in group 1. TFF3 was found have the highest AUC (0.9198) on ROC curve for predicting progressive functional deterioration. Urinary TFFs, NGAL, and microalbumin significantly correlate with progressive deterioration of kidney function in children harboring CAKUT. TFF3, with the strongest prediction of functional deterioration, is an emerging peptide showing sufficient potential to be included in the biomarker panel. Graphical abstract.

Left ventricular myocardial strain assessed by cardiac magnetic resonance feature tracking in patients with rheumatoid arthritis

PurposeThe aim of the study was to assess a relationship between the occurrence of rheumatoid arthritis (RA) and its selected clinical parameters, and left ventricular myocardial strain.Material and methodsFifty-six subjects were qualified for the study: 30 RA patients and 26 subjects without rheumatoid diseases. The study design included taking medical history, assessment of the disease activity using selected scales of activity, collecting samples of venous blood to assess selected laboratory parameters and the assessment of cardiac magnetic resonance (CMR). Using the feature tracking method, the following parameters of the left ventricular myocardial strain were assessed: longitudinal strain (LS), radial strain (RS) and circumferential strain (CS).ResultsRegarding global values, peak LS and peak CS were statistically significantly lower in RA patients than in the control group. In the whole study group, the factors independently related to low global LS peaks were as follows: occurrence of RA, occurrence of arterial hypertension, increased activity of antibodies against cyclic citrullinated peptide and increased concentration of neutrophil gelatinase-associated lipocalin. The occurrence of RA, occurrence of diabetes, tobacco smoking, higher activity of antibodies against cyclic citrullinated peptide and current use of methotrexate are the risk factors for low peak of global CS. The current use of steroids constitutes a protecting factor against low global CS peaks.ConclusionIn subjects with no clinically manifested cardiac damage, RA is associated with a deteriorated left ventricular systolic function assessed by left ventricular myocardial strain measured by CMR feature tracking.

Biomarkers of acute kidney injury in patients with nephrotic syndrome.

ABSTRACTIntroduction:Emergence of acute kidney injury (AKI) in patients with nephrotic syndrome (NS) requires prompt diagnosis and differentiation between acute tubular necrosis (ATN) and proliferative glomerulonephritis. We studied the potential use of commercial urinary biomarkers' tests in the diagnosis of AKI in patients with NS.Methods:A cross sectional estimate of urinary concentrations of KIM-1 and NGAL was performed in 40 patients with NS: 9 with proliferative glomerulopathy, being 4 with AKI and 31 without proliferative glomerulopathy, being 15 with AKI. AKI was defined using the KDIGO criteria.Results:The mean age was 35 ± 16 years. The main diagnoses were focal and segmental glomerulosclerosis (10, 25%), membranous glomerulopathy (10, 25%), minimal change disease (7, 18%), lupus nephritis (6, 15%), and proliferative glomerulonephritis (3, 8%). Patients with ATN had higher levels of urinary KIM-1 (P = 0.0157) and NGAL (P = 0.023) than patients without ATN. The urinary concentrations of KIM-1 (P= 0.009) and NGAL (P= 0.002) were higher in patients with AKI than in patients without AKI. Urinary NGAL and KIM-1 levels were significantly higher in patients with ATN without proliferative glomerulonephritis than in patients with proliferative glomerulonephritis (P = 0.003 and P=0.024, respectively).Conclusions:Neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) estimates correlated with histological signs of ATN and were able to discriminate patients with AKI even in conditions of NS. Furthermore, urinary levels of NGAL and KIM-1 may be useful in the differential diagnosis of acute tubular necrosis and exudative glomerulonephritis in patients with nephrotic syndrome.

INFORMATIVITY OF RADIONUCLIDE RENAL SCINTIGRAPHY AND BIOCHEMICAL MARKERS IN DETECTION OF RENAL DYSFUNCTION IN PATIENTS UNDERGOING MYOCARDIAL REVASCULARIZATION

A cute renal injury (AKI) is a common complication of cardiac surgery. Diagnostic criteria of acute renal dysfunction based on serum creatinine concentrations do are not suitable for early detection of AKI. Purpose. To evaluate the diagnostic significance of radionuclide scintigraphy and biochemical markers in the detection of renal dysfunction in patients with coronary artery disease (CAD) in the early postoperative period after coronary artery bypass grafting (CABG). Material and methods. A randomized controlled trial comprised a total of 108 CAD patients (all men aged 54.94 ± 0.72 years) who underwent direct myocardial revascularization by CABG. All patients received dynamic renal scintigraphy with 99mТс-DTPA and blood tests measuring serum concentrations of creatinine, lipocalin (NGAL), and Cystatin C before and after CABG. Results. After CABG, the mean values of total glomerular filtration rate (GFR) and GFR for each kidney significantly decreased whereas the serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and Cystatin С in blood serum significantly increased. In the postoperative period, the creatinine clearance also significantly decreased. Statistical analysis revealed direct correlations of cardiopulmonary bypass duration with the changes in GFR (R = 0.42; P = 0.017) and s-NGAL (R = 0.39, P = 0.02) in cardiac surgery patients. Conclusion. Radionuclide method is not inferior to testing biochemical markers in the evaluation of early postoperative renal dysfunction in regard to diagnostic value and informativeness.

Urinary calprotectin, NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases

Introduction It has been demonstrated that urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin are helpful biomarkers in the differentiation of intrinsic and prerenal acute kidney injury. Objective The present cross-sectional study investigates, whether urinary biomarkers are able to differentiate primarily inflammatory from non-inflammatory entities in chronic kidney disease (CKD). Methods Urinary calprotectin, NGAL, and kidney injury molecule-1 (KIM-1) concentrations were assessed in a study population of 143 patients with stable CKD and 29 healthy controls. Stable renal function was defined as an eGFR fluctuation ≤5 ml/min/1.73 m2 in the past 12 months. Pyuria, metastatic carcinoma, and renal transplantation were regarded as exclusion criteria. Diabetic nephropathy, hypertensive nephropathy, and polycystic kidney disease were categorized as ‘primarily non-inflammatory renal diseases’ (NIRD), whereas glomerulonephritis and vasculitis were regarded as ‘primarily inflammatory renal diseases’ (IRD). Results Urinary calprotectin and NGAL concentrations significantly differed between CKD and healthy controls (p < 0.05 each), whereas KIM-1 concentrations did not (p = 0.84). The three biomarkers did neither show significant differences in-between the individual entities, nor the two categories of IRD vs. NIRD (calprotectin 155.7 vs. 96.99 ng/ml; NGAL 14 896 vs. 11 977 pg/ml; KIM-1 1388 vs. 1009 pg/ml; p > 0.05 each). Albumin exceeds the diagnostic power of the investigated biomarkers by far. Conclusions The urinary biomarkers calprotectin, NGAL, and KIM-1 have no diagnostic value in the differentiation of primarily inflammatory vs. non-inflammatory etiologies of CKD.

Cardiac Inflammation, Oxidative Stress, Nrf2 Expression, and Coagulation Events in Mice with Experimental Chronic Kidney Disease.

Chronic kidney disease (CKD) is known to be associated with cardiovascular dysfunction. Dietary adenine intake in mice is also known to induce CKD. However, in this experimental model, the mechanisms underlying the cardiotoxicity and coagulation disturbances are not fully understood. Here, we evaluated cardiac inflammation, oxidative stress, DNA damage, and coagulation events in mice with adenine (0.2% w/w in feed for 4 weeks)-induced CKD. Control mice were fed with normal chow for the same duration. Adenine increased water intake, urine output, relative kidney weight, the plasma concentrations of urea and creatinine, and the urinary concentrations of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It also decreased the body weight and creatinine clearance, and caused kidney DNA damage. Renal histological analysis showed tubular dilation and damage and neutrophilic influx. Adenine induced a significant increase in systolic blood pressure and the concentrations of troponin I, tumor necrosis factor-α, and interleukin-1β in heart homogenates. It also augmented the levels of markers of lipid peroxidation measured by malondialdehyde production and 8-isoprostane, as well as the antioxidants superoxide dismutase and catalase. Immunohistochemical analysis of the hearts showed that adenine increased the expression of nuclear factor erythroid-derived 2-like 2 by cardiomyocytes. It also caused cardiac DNA damage. Moreover, compared with the control group, adenine induced a significant increase in the number of circulating platelet and shortened the thrombotic occlusion time in pial arterioles and venules in vivo, and induced a significant reduction in the prothrombin time and activated partial thromboplastin time. In conclusion, the administration of adenine in mice induced CKD-associated cardiac inflammation, oxidative stress, Nrf2 expression, and DNA damage. It also induced prothrombotic events in vivo. Therefore, this model can be satisfactorily used to study the cardiac pathophysiological events in subjects with CKD and the effect of drug treatment thereon.

Evaluation of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels, and their relations with disease type and activity in inflammatory bowel diseases

Inflammatory bowel disease (IBD) mainly encompass two entities called ulcerative colitis (UC) and Crohn's disease (CD), both of which are chronic, progressive and, inflammatory conditions of the gastrointestinal tract. Various indicators and non-invasive markers have been sought and used in IBD patients to help assessing disease activity and treatment effectiveness although none of them are proven to yield definite results in full correlation with the clinical, endoscopic, and histopathological examinations. The aim of the current study was to investigate the relationship of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels with disease type and activity and to assess their potential use in establishing diagnosis and activity status of IBD, namely UC and CD. A total of 111 IBD patients with determined active and inactive disease periods and 70 matched controls were recruited. Serum NGAL levels of the patients and the control group were measured using commercially available ELISA kits. ADMA and SMDA levels were measured by high performance liquid chromatography. The IBD group had significantly higher serum levels of NGAL (p = 0.001), ADMA (p = 0.0001), and SDMA (p = 0.0001) in comparison to the control group. Likewise, serum NGAL, ADMA, and SDMA levels were significantly higher in the active IBD group compared to the inactive IBD group (p = 0.0001). Active UC and active CD patients similarly had significantly higher levels of serum NGAL, ADMA, and SDMA than the respective levels in inactive UK and inactive CD patients (p = 0.0001). Serum NGAL, ADMA and SMDA levels are increased in patients with IBD, and serum NGAL, ADMA and SMDA concentrations are significantly higher in active IBD patients than inactive IBD patients. Our results suggest these biomarkers may serve in estimating IBD activity and severity.

Yoğun Bakımda Akut Böbrek Hasarı Takibinde NGAL, Kreatinin ve Renal Kan Akımının Monitörizasyonu

Objectıve: Acute Kidney Injury (AKI) and subsequent renal failure are the leading causes of morbidity and mortality in the intensive care unit (ICU). In this study, it was planned to compare Neutrophil Gelatinase-associated Lipocalin (NGAL) and creatinine values in patients diagnosed with AKI and to determine the effect of renal dose dopamine use on renal blood flow, development of chronic renal failure (CRF) and mortality. Materıals and methods: This prospective study was planned with 35 patients developed AKI in the ICU of Bakırköy Dr. Sadi Konuk Training and Research Hospital. The patients were randomized into 2 groups as 18 patients who received dopamine treatment with the recommendation of the cardiology clinic and 17 patients who did not receive dopamine treatment. Urea, creatinine and NGAL plasma levels were compared between groups. Results: There was no difference between the groups in terms of age, gender and AKI stage. The 0th, 24th hour results and 24-hour changes of urea, creatinine and NGAL values of dopamine patient, who took dopamine, were found to be similar to those of patients who did not take dopamine. A significant positive correlation was found between the 24-hour change in creatinine value and the 24-hour change in NGAL (r=0.374; p&lt;0.05). There was no significant change in the diameter and flow of renal arteries between measurements in patients who received dopamine. The rates of patients who regain normal kidney functions, develop CRF or develop mortality between the two groups were found to be similar. Conclusıon: Treatment results of AKI developing in ICU are not satisfactory. Low-dose dopamine treatment has no effect on patient outcomes in these patients. NGAL is a biomarker that has the ability to show renal damage at an early stage. Serial measurement of NGAL concentration during ICU stay may benefit the clinician in early diagnosis and follow-up of AKI.

Elevated plasma level of neutrophil gelatinase-associated lipocalin (NGAL) in patients with breast cancer.

Background: Neutrophil gelatinase‑associated lipocalin (NGAL), also known as lipocalin 2, siderocalin, 24p3 or uterocalin, plays a key role in inflammation and in different types of cancer. In this study, we investigated whether plasma NGAL levels were altered in patients with breast cancer. The relationship between plasma NGAL levels and pretreatment hematologic profile was also explored.Methods: Plasma NGAL concentrations were measured using ELISA in breast cancer patients and control subjects. A total of 75 patients with breast cancer and 65 age- and body mass index-matched control subjects were studied. All of the study subjects were female.Results: Plasma NGAL level was found to be elevated in the patients with breast cancer compared to the control subjects (94.3 ng/mL (interquartile range 39.3-207.6) vs. 55.0 ng/mL (interquartile range 25.8-124.7), p = 0.007). Multiple logistic regression analysis revealed that NGAL was independently associated with breast cancer, even after adjusting for known biomarkers. Furthermore, NGAL level was elevated in the breast cancer patients who were negative progesterone receptor status, had a histologic grade ≥ 2, clinical stage III, and pathologic stage T2+T3+T4. In addition, NGAL level was significantly correlated with white blood cell (WBC) count, monocyte count, neutrophil count, and platelet count (all p < 0.01). Moreover, WBC count, neutrophil count, monocyte count, lymphocyte count, platelet count, and NGAL level gradually increased as the stage progressed.Conclusions: Increased plasma NGAL levels were associated with breast cancer independently of risk factors, and were correlated with inflammatory biomarkers. These results suggest that NGAL may act through inflammatory reactions to play an important role in the pathogenesis of breast cancer.

Urinary NGAL Measured after the First Year Post Kidney Transplantation Predicts Changes in Glomerular Filtration over One-Year Follow-Up.

Currently, serum creatinine and estimated glomerular filtration rate (eGFR) together with albuminuria or proteinuria are laboratory markers used in long-term monitoring of kidney transplant recipients. There is a need for more sensitive markers that could serve as early warning signs of graft dysfunction. Our aim was to assess the urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of changes in kidney transplant function after the first year post-transplantation. We prospectively recruited 109 patients with functioning graft at least one year after the transplantation, with no acute conditions over the past three months, during their control visits in kidney transplant ambulatory. Urinary NGAL measured on recruitment was twice higher in patients with at least 10% decrease in eGFR over 1-year follow-up compared to those with stable or improving transplant function. Baseline NGAL significantly predicted the relative and absolute changes in eGFR and the mean eGFR during the follow-up independently of baseline eGFR and albuminuria. Moreover, baseline NGAL significantly predicted urinary tract infections during the follow-up, although the infections were not associated with decreasing eGFR. Additionally, we assessed urinary concentrations of matrix metalloproteinase 9—NGAL complex in a subgroup of 77 patients and found higher levels in patients who developed urinary tract infections during the follow-up but not in those with decreasing eGFR. High urinary NGAL in clinically stable kidney transplant recipients beyond the first year after transplantation may be interpreted as a warning and trigger the search for transient or chronic causes of graft dysfunction, or urinary tract infection.

Rapid Multianalyte Microfluidic Homogeneous Immunoassay on Electrokinetically Driven Beads.

The simplicity of homogeneous immunoassays makes them suitable for diagnostics of acute conditions. Indeed, the absence of washing steps reduces the binding reaction duration and favors a rapid and compact device, a critical asset for patients experiencing life-threatening diseases. In order to maximize analytical performance, standard systems employed in clinical laboratories rely largely on the use of high surface-to-volume ratio suspended moieties, such as microbeads, which provide at the same time a fast and efficient collection of analytes from the sample and controlled aggregation of collected material for improved readout. Here, we introduce an integrated microfluidic system that can perform analyte detection on antibody-decorated beads and their accumulation in confined regions within 15 min. We employed the system to the concomitant analysis of clinical concentrations of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Cystatin C in serum, two acute kidney injury (AKI) biomarkers. To this end, high-aspect-ratio, three-dimensional electrodes were integrated within a microfluidic channel to impart a controlled trajectory to antibody-decorated microbeads through the application of dielectrophoretic (DEP) forces. Beads were efficiently retained against the fluid flow of reagents, granting an efficient on-chip analyte-to-bead binding. Electrokinetic forces specific to the beads’ size were generated in the same channel, leading differently decorated beads to different readout regions of the chip. Therefore, this microfluidic multianalyte immunoassay was demonstrated as a powerful tool for the rapid detection of acute life-threatening conditions.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) Is Related with the Proteinuria Degree and the Microscopic Kidney Findings in Leishmania-Infected Dogs.

Early diagnosis of renal damage in Leishmania infected dogs may allow appropriate treatments and prevent some deaths. This study investigates neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney disease in dogs experimentally infected with Leishmania infantum. Serum, urine, and kidney samples were collected from 30 infected beagle dogs and six uninfected control dogs. Based on proteinuria and azotemia values, dogs were initially classified. NGAL was measured in urine and serum samples. Then, the urinary NGAL to creatinine ratio (uNGAL/C) was calculated. Kidney samples were taken for histopathological studies, and the dogs were classified according to the severity of glomerular and tubulointerstitial lesions. In Leishmania-infected dogs, the uNGAL/C was significantly higher in proteinuric non-azotemic dogs compared with non-proteinuric non-azotemic dogs (p = 0.038). Serum NGAL (sNGAL) concentration did not differ between groups. Microscopic studies revealed several degrees of glomerulonephritis and slight focal lymphoplasmacytic interstitial nephritis in 89% and 55% of infected dogs, respectively. Urinary protein to creatinine ratio (UPC) and uNGAL/C were significantly higher in dogs with affected glomeruli compared to infected dogs without renal lesions (p = 0.045 and p = 0.043, respectively). The results show that uNGAL/C correlates with proteinuria and the presence of moderate glomerular lesions in non-azotemic dogs experimentally infected with L. infantum.

Urine neutrophil gelatinase-associated lipocalin concentration in healthy newborns during the first three postnatal days.

IntroductionUrine neutrophil gelatinase-associated lipocalin (uNGAL) is a biochemical marker significant for early prediction of acute kidney injury in adults. However, it has not been examined sufficiently among the infant population, particularly newborns in terms of reference values. The aim of our study was to determine the concentration of uNGAL in healthy term newborns and to determine if there was a difference in uNGAL concentration according to gender, postnatal age and birth weight.Materials and methodsOur study involved 81 healthy term newborns birth (≥ 37 weeks, Apgar score ≥ 8 in the first minute after birth, CRP < 5 mg/L). Urine NGAL was measured using chemiluminescent microparticle immunoassay (CMIA) within 72 hours after birth, on Architect plus ci8200 analyser (Abbott, Chicago, USA). Data were analysed using Statistica software.ResultsThe median concentration of uNGAL in the whole study group of healthy term newborns was 27.1 ng/mL (16.5-56.0 ng/mL) (newborn girls, 27.1 ng/mL (15.8-47.9 ng/mL); newborn boys, 27.9 ng/mL (16.5-61.0 ng/mL), P = 0.941). Median uNGAL concentration according to postnatal age expressed in days was 28.2 ng/mL (11.7-57.2 ng/mL) 1st day, 28.9 ng/mL (16.5-64.2 ng/mL) 2nd day and 23.9 ng/mL (20.2-46.6) 3rd day, P = 0.863. Regarding birth weight for newborns < 3500 g, median concentration was 25.0 ng/mL (16.5-45.4 ng/mL) and for weight ≥ 3500 g 30.6 ng/mL (16.5-64.2 ng/mL), P = 0.455.ConclusionsThere were no significant difference in uNGAL concentration in relation to gender, postnatal age and birth weight.

Association of Longitudinal Changes in Symptoms and Urinary Biomarkers in Patients with Urological Chronic Pelvic Pain Syndrome: A MAPP Research Network Study.

We analyzed a series of novel noninvasive urinary biomarkers for their ability to objectively monitor the longitudinal clinical status of patients with urological chronic pelvic pain syndrome. Baseline, 6 and 12-month urine samples were collected (216) and used to quantify vascular endothelial growth factor, vascular endothelial growth factor (VEGF) receptor 1 (R1), neutrophil gelatinase associated lipocalin (NGAL), matrix metalloproteinase-2, matrix metalloproteinase (MMP)-9, and MMP-9/NGAL complex by enzyme-linked immunosorbent assays. Patient symptom changes were classified as improved, stable or worse using a functional clustering algorithm. Proportional odds models were used to evaluate the association between symptom change and urinary biomarkers. Across all sampled participants, longitudinal decreases in normalized VEGF concentration (pg/μg) were associated with pain severity improvement, and decreases in MMP-9, NGAL and VEGF-R1 concentration (pg/ml) as well as NGAL normalized concentration were associated with improved urinary symptoms. Longitudinal decreases in normalized VEGF-R1 were associated with pain improvement in patients with moderate widespreadness, no bladder symptoms and no painful filling. Lower baseline normalized VEGF-R1 concentration was associated with pain improvement in patients with pelvic pain only. Higher baseline MMP-9/NGAL levels were associated with pain and urinary improvement across all participants. Moreover, longitudinal increases in MMP-2 concentration was associated with improved pain in men and patients with painful filling. Our results suggest these urinary biomarkers may be useful in monitoring urological chronic pelvic pain syndrome symptom changes with respect to both urinary severity and pain severity. With further testing, they may represent objective biological measures of urological chronic pelvic pain syndrome progression and/or resolution while also providing insight into the pathophysiology of urological chronic pelvic pain syndrome.