Neutrophil Gelatinase-associated Lipocalcin Research Articles

Acute kidney injury in critically ill obstetric patients: Incidence and role of neutrophil gelatinase-associated lipocalcin - A prospective observational cohort study.

Data focussing on acute kidney injury (AKI) in obstetric patients admitted to the intensive care unit (ICU) are scarce and even more so regarding the role of neutrophil gelatinase-associated lipocalcin (NGAL) in detecting AKI or predicting outcomes in these patients. Hence, we aim to evaluate the incidence of AKI in obstetric ICU patients and validate the role of urinary and serum NGAL in predicting the onset of AKI and mortality. This prospective observational cohort included 45 obstetric patients admitted in ICU, excluding those with prior renal dysfunction. Serum creatinine and urine output were monitored for the occurrence of AKI during the ICU stay. The outcome of the patient (survival or death) in the ICU and hospital was recorded, and serum and urinary NGAL were determined at the time of ICU admission. AKI occurred in 32 [71.1%; 95% confidence interval (CI): 55.4%, 86.8%] patients during their ICU stay. Serum NGAL showed an area under receiver operating characteristic curve (AUROCC) of 0.630 (95% CI: 0.417, 0.842) (P = 0.231) for AKI and 0.486 (95% CI: 0.295, 0.676) (P = 0.883) for ICU mortality. Urinary NGAL showed AUROC = 0.472 (95% CI: 0.285, 0.660) (P = 0.772) to predict AKI and 0.430 (95% CI: 0.268, 0.652) (P = 0.684) for ICU mortality. AKI is common amongst critically ill obstetric ICU patients. However, serum and urinary NGAL cannot be advocated to discriminate between patients with or without AKI or between survivors and non-survivors in critically ill obstetric patients.

Copeptin as a potential biomarker of chronic kidney disease to predict the disease progression in children with chronic kidney disease.

Biomarkers to predict the onset and progression of chronic kidney disease (CKD) in children are lacking, and no such definite biomarkers have been implicated in the diagnosis of CKD. We conducted this study to evaluate copeptin as a CKD marker and predict the disease progression by estimating the copeptin levels at baseline and 12 months follow-up in children with CKD stage 2 and above. This prospective single-centre cohort study was conducted in children under 14 years with CKD stages 2-4. Blood and urine samples were collected at enrolment and 1-year follow-up for routine investigations and serum copeptin, cystatin C and urinary neutrophil gelatinase-associated lipocalcin (uNGAL) estimation. A total of 110 children (60 cases and 50 controls) were enrolled in the study. The mean estimated glomerular filtration rate (eGFR) of cases was 58.3 ± 18.7 ml/min/1.73 m2. Among the cases, there was a significant rise in the serum copeptin levels from baseline 483.08 ± 319.2 pg/ml to follow-up at 1 year, that is, 1046.82 ± 823.53 pg/ml (P < 0.0001). A significant difference was noted in the baseline values of serum cystatin C, that is, 1512.98 ± 643.77 ng/ml and 719.68 ± 106.96 ng/ml (P < 0.0001), and uNGAL, that is, 13.53 ± 11.72 and 1.76 ± 2.37 ng/ml (P < 0.0001) between the cases and controls. There was no significant correlation (correlation coefficient = 0.10) between change in eGFR and copeptin levels during 12 months of follow-up. No significant correlation was found between the change in eGFR and copeptin levels during 12 months of follow-up. This can be due to the slow deterioration of renal functions, as most of the cases had underlying congenital anomalies of the kidney and urinary tract (CAKUT), which is known to have a slow progression of CKD and a small sample size.

Role of Urinary Biomarker Neutrophil Gelatinase Associated Lipocalcin (NGAL) in Differentiating Acute Tubular Necrosis (ATN) and Non-acute Tubular

Role of Urinary Biomarker Neutrophil Gelatinase Associated Lipocalcin (NGAL) in Differentiating Acute Tubular Necrosis (ATN) and Non-acute Tubular

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis.

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

Acute Kidney Injury in Severe Preeclamptic Patients Admitted to Intensive Care Unit: Epidemiology and Role of Serum Neutrophil Gelatinase-associated Lipocalcin.

BackgroundPatients with preeclampsia admitted to the intensive care unit (ICU) may have risk factors for acute kidney injury (AKI). Although the use of neutrophil gelatinase-associated lipocalcin (NGAL) to predict AKI is previously validated, we could locate only scanty data regarding the epidemiology of AKI and role of NGAL in preeclamptic patients admitted to ICU.MethodsPatients with preeclampsia admitted to our ICU were included. The incidence and severity of AKI during the entire ICU stay were assessed using kidney disease improving global outcomes criteria, while the a priori risk factors and serum NGAL were also evaluated.ResultsA total of 52 preeclamptic patients admitted to ICU were included, among whom the majority had eclampsia (75%). AKI developed in 25 (48.1%) patients with stages 1, 2, and 3 in 56, 36, and 8%, respectively. The incidence of sepsis (16 vs 0%), shock (40 vs 7.4%), and anemia (84 vs 59.3%) was significantly greater in patients with AKI (p < 0.05). ICU mortality (28 vs 3.7%), duration of ICU, and hospital stay were significantly higher in patients who developed AKI (p < 0.05). There was no association of serum NGAL [274 (240–335) ng/mL] with AKI or the mortality (p = 0.725, 0.861); there was, however, a significant discriminatory value for eclampsia [p = 0.019; area under curve = 0.736 (95% confidence interval: 0.569–0.904)].ConclusionsAlthough AKI is common among patients with preeclampsia admitted to ICU, serum NGAL does not predict its occurrence.How to cite this articleTyagi A, Yadav P, Salhotra R, Das S, Singh PK, Garg D. Acute Kidney Injury in Severe Preeclamptic Patients Admitted to Intensive Care Unit: Epidemiology and Role of Serum Neutrophil Gelatinase-associated Lipocalcin. Indian J Crit Care Med 2021;25(9):1013–1019.

ABSTRACTS CRITICARE – IJCCM2021

IntroductionCritically ill preeclamptic patients may have risk factors for acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalcin (NGAL) is a validated biomarker to predict AKI. We could locate scanty data regarding the epidemiology of AKI and the role of NGAL in preeclamptic patients admitted to ICU.Materials and methodsPreeclamptic patients admitted to multidisciplinary ICU were included. The occurrence of AKI and its severity for the entire ICU stay using KDIGO criteria, risk factors, and serum NGAL were assessed.ResultsFrom 52 preeclamptic patients admitted to ICU, majority had eclampsia (75%). The ICU mortality was 15.4%. AKI developed in 25 (48.1%) patients; with stage 1, 2 and 3 in 56%, 36% and 8% respectively. Incidence of sepsis (16% versus 0%), shock (40% versus 7.4%), and anaemia (84% versus 59.3%) was significantly greater in patients with AKI (P < 0.05). ICU mortality (28% versus 3.7%), duration of ICU and hospital stay were significantly higher in preeclamptics with AKI (P < 0.05). Serum NGAL (274 [240-335] ng/ml) showed no association with AKI or mortality (P = 0.725, 0.861); but significant prediction for eclampsia [P = 0.019; AUC = 0.736 (95% CI: 0.569 – 0.904)].DiscussionsThe present prospective cohort study aimed to evaluate AKI in a specific subset of critically ill obstetric patients viz., those with preeclampsia. While there is little previous data on AKI in critically ill preeclamptic patients, it has been evaluated among those with the disease but not admitted to ICU.11–13 The incidences herein were reported in a lower percentage than our results viz., 15.3 and 17%.11,12 The much greater incidence noted by us can be attributed to an increased presence of risk factors for AKI encountered in those admitted to the ICU, such as, sepsis and shock.ConclusionAKI is common among preeclamptic patients admitted to ICU, but serum NGAL does not predict AKI in these patients.

Serum neutrophil gelatinase-associated lipocalin as an early biomarker of acute kidney injury in subjects undergoing percutaneous transluminal coronary angiogram with normal EGFR

Introduction: Detecting AKI in a timely fashion with the current AKIN staging criteria is a challenge because the diagnosis of AKI is usually based on changes in serum creatinine (SCr) which is a poor marker of early renal dysfunction. Aim: To study the role of Serum Neutrophil Gelatinase-Associated Lipocalcin (NGAL) as early biomarker for the detection of Contrast induced acute kidney injury (CIAKI) in subjects undergoing Percutaneous transluminal coronary angiogram (PTCA) with normal eGFR. Materials and Methods: Prospective cohort study was conducted, where SCr and serum NGAL were serially measured in a heterogeneous group of subjects (n=60) presenting to cardiology department. Results: The study population consisted of 60 subjects. All subjects were divided into 2 groups “CIAKI group” and “no-CIAKI group” according to predefined definition. The serum NGAL increased and reached its peak at 4 hours after contrast media (CM) administration and did not returned to baseline by 24 hours while the SCr increased at 24 hours and reached peak at 48 hours respectively (P

Adaptive Autophagy Offers Cardiorenal Protection in Rats with Acute Myocardial Infarction.

Objective Understanding the multifactorial changes involved in the kidney and heart after acute myocardial infarction (AMI) is prerequisite for further mechanisms and early intervention, especially autophagy changes. Here, we discussed the role of adaptive autophagy in the heart and kidney of rats with AMI. Methods A rat model of AMI was established by ligating the left anterior descending branch of the coronary artery. Animals were sacrificed at 2 and 4 weeks after the operation to assess the morphological and functional changes of the heart and kidney, as well as the autophagy pathway. In vitro, HK-2 and AC16 cell injuries and the autophagy pathway were assayed after autophagy was inhibited by 3-methyladenine (3-MA) in a hypoxia incubator. Results We found that the left ventricular systolic pressure (LVSP) significantly decreased in the model group at weeks 2 and 4. At weeks 2 and 4, the level of urinary kidney injury molecule 1 (uKIM1) of the model group was significantly higher than the sham group. At week 4, urinary neutrophil gelatinase-associated lipocalcin (uNGAL) and urinary albumin also significantly increased. At week 2, microtubule-associated protein 1 light chain 3-II (LC3-II), ATG5, and Beclin1 were significantly elevated in the heart and kidney compared with the sham-operated rats, but there was no change in p62 levels. At week 4, LC3-II did not significantly increase and p62 levels significantly increased. In addition, 3-MA markedly increased KIM1, NGAL, and the activity of caspase-3 in the hypoxic HK-2 and AC16 cell. Conclusion Autophagy will undergo adaptive changes and play a protective role in the heart and kidney of rats after AMI.

Neutrophil gelatinase-associated lipocalcin (NGAL) as a biomarker of dialysis-dependent acute kidney injury following infrarenal aortic surgery

Introduction Abdominal aortic surgery (AAS) is a high-risk procedure with a relatively high incidence of postoperative acute kidney injury (AKI). The diagnosis of AKI has traditionally been based on an increase in se-creatinine. However, se-creatinine may not increase until up to 50% of the kidney function is lost [1-4] making timely

Characteristics of changes in urinary NGAL, KIM-1 and IL-18 in Phytolaccae Radix-induced renal injury in rats and significance of combined detection

To explore the characteristics of changes in neutrophil gelatinase-associated lipocalcin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) in Phytolaccae Radix-induced kidney injury in rats and the significance of the combined detection. Wistar rats were divided into three groups: high and low dose (crude drug 40, 20 g x kg(-1) x d(-1)) Phytolaccae Radix decoction groups and the control group, and orally administrated with distilled water or equal volume of Phytolaccae Radix decoction for 35 consecutive days. Their blood and urine samples were collected on day 7, 14, 21, 28, 35,42. The anatomical analysis was conducted for each group. The contents of serum total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CR) and urinary TP and ALB were detected-by means of biochemical analyzer. The concentrations of urinary NGAL, KIM-1 and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of renal pathology were observed by light or electron microscopy. The curve areas of various serum or urine indexes and the combined detection were compared by receiver operating characteristic curve (ROC curve). Rats were given Phytolaccae Radix decoction at the doses of 40, 20 g crude drug/kg daily for 35 consecutive days to induce kidney injury characterized by the degeneration of renal tubular epithelial cell and protein cast. The injury was partially reversible during the recovery period. Compared with the control group, the content of serum BUN, CR and urinary TP in each dose group mostly showed a downward trend. On day 21, the content of urinary ALB obviously increased till the end of administration. The contents of urinary NGAL, KIM-1 and IL-18 began increasing on day 7. Since day 14, high and low dose groups showed significant difference (P<0.01). The high dose group even showed notable changes during the recovery period. According to ROC analysis, the curve areas of NGAL, KIM-1 and IL-18 were 0.846, 0.837 and 0.863 (P <0.01), respectively, much higher than that of BUN and CR. The area of the combined detection was up to 0.947. Urinary NGAL, IL-18 and KIM-1 could forecast and indicate the occurrence and development of renal injury to some degree, and show higher sensitivity and site specificity. The combined detection could further improve the test efficiency.

Elevated urinary neutrophil gelatinase‐associated lipocalcin after acute heart failure treatment is associated with worsening renal function and adverse events

Reliable detectors of worsening renal function (WRF) in Emergency Department (ED) patients with acute heart failure (AHF) are limited. We hypothesized that initial urinary neutrophil gelatinase-associated lipocalcin (NGAL) levels, and changes in urinary NGAL levels after initial ED AHF therapy, would be associated with WRF and adverse events. Urinary NGAL upon ED presentation and 12-24 h after ED treatment was measured in a cohort of ED patients with AHF. NGAL was corrected for urinary creatinine (uCr). WRF was defined as RIFLE stages 1, 2, or 3, or a creatinine increase of ≥0.3 mg/dL. Patients were prospectively followed for 5- and 30-day adverse cardiovascular events. The 399 patients had a median age of 63 years, 50% were Caucasian, and 62% were male. Those with WRF at 72-96 h were more likely to have a higher initial NGAL value (71 vs. 32 ng NGAL/mg uCr) (P = 0.005), and a higher NGAL level at 12-24 h after ED therapy (107 vs. 25ng NGAL/mg uCr, P < 0.001). In a multivariable model, NGAL at 12-24 h remained a significant predictor of WRF (P = 0.012). Of all variables available 12-24 h after initial therapy, the only significant predictor of 30-day events was an elevated urinary NGAL level (P = 0.02). Urinary NGAL levels determined 12-24 h after ED therapy are significantly associated with both WRF at 72-96 h and 30-day adverse events. This suggests that early management strategies may have an impact on subsequent WRF and outcomes. If confirmed, NGAL may have a role for guiding therapeutic decisions.

Laboratory prediction of the requirement for renal replacement in acute falciparum malaria

BackgroundAcute renal failure is a common complication of severe malaria in adults, and without renal replacement therapy (RRT), it carries a poor prognosis. Even when RRT is available, delaying its initiation may increase mortality. Earlier identification of patients who will need RRT may improve outcomes.MethodProspectively collected data from two intervention studies in adults with severe malaria were analysed focusing on laboratory features on presentation and their association with a later requirement for RRT. In particular, laboratory indices of acute tubular necrosis (ATN) and acute kidney injury (AKI) that are used in other settings were examined.ResultsData from 163 patients were available for analysis. Whether or not the patients should have received RRT (a retrospective assessment determined by three independent reviewers) was used as the reference. Forty-three (26.4%) patients met criteria for dialysis, but only 19 (44.2%) were able to receive this intervention due to the limited availability of RRT. Patients with impaired renal function on admission (creatinine clearance < 60 ml/min) (n = 84) had their laboratory indices of ATN/AKI analysed. The plasma creatinine level had the greatest area under the ROC curve (AUC): 0.83 (95% confidence interval 0.74-0.92), significantly better than the AUCs for, urinary sodium level, the urea to creatinine ratio (UCR), the fractional excretion of urea (FeUN) and the urinary neutrophil gelatinase-associated lipocalcin (NGAL) level. The AUC for plasma creatinine was also greater than the AUC for blood urea nitrogen level, the fractional excretion of sodium (FeNa), the renal failure index (RFI), the urinary osmolality, the urine to plasma creatinine ratio (UPCR) and the creatinine clearance, although the difference for these variables did not reach statistical significance.ConclusionsIn adult patients with severe malaria and impaired renal function on admission, none of the evaluated laboratory indices was superior to the plasma creatinine level when used to predict a later requirement for renal replacement therapy.

Safety of Low Volume Iodinated Contrast Administration for Arteriovenous Fistula Intervention in Chronic Kidney Disease Stage 4 or 5 Utilizing a Bicarbonate Prophylaxis Strategy

Efforts to increase the number of functioning arteriovenous fistulas in chronic kidney disease (CKD) stages 4 and 5 have been impacted by concerns about the risk for contrast-induced nephropathy during diagnostic and interventional procedures for poorly developed fistulas. We conducted a prospective observational study of low volume iodinated contrast administration for fistulography and angioplasty in a CKD stage 4 and stage 5 population pretreated with a sodium bicarbonate protocol. Acute kidney injury was assessed by change in serum creatinine and urinary neutrophil-gelatinase associated lipocalcin (NGAL). Only 1/18 patients (5.5%) developed acute kidney injury as defined by change in serum creatinine 48 hours after contrast exposure. No patients demonstrated significant change in urinary NGAL at 3 or 48 hours after procedure, nor did any require acute initiation of dialysis. Fistulography alone, or with angioplasty, utilizing a low volume of iodinated contrast and sodium bicarbonate solution for prophylaxis, appears to be safe in the CKD stages 4 and 5 population.

Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury

Diarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure. Neutrophil gelatinase-associated lipocalcin (NGAL) is an early indicator of kidney injury. To determine if urinary NGAL excretion is a biomarker of severe renal injury and predicts the need for dialysis in D+HUS. Patients were randomly selected from among participants in the SYNSORB Pk trial. Urine samples were collected daily if available during the first week of hospitalization. NGAL levels were determined by ELISA. 34 children, age 5.9+/-3.9 yr, were studied; ten (29%) required dialysis. Patients were categorized based on urinary NGAL concentration within five days of hospitalization - <200 ng/ml and >or=200 ng/ml. Twenty patients (58%) had increased urinary NGAL excretion. The severity of D+HUS at enrollment was similar in the two groups. However, children with increased urinary NGAL levels had higher peak BUN and creatinine concentrations (P<0.01) and required dialysis more often, 9/20 versus 1/14 (P=0.024) compared to children with normal excretion. The majority of patients with D+HUS have renal tubular epithelial injury, as evidenced by elevated urinary NGAL excretion. Urinary NGAL levels below 200 ng/ml within five days of hospitalization may be an adjunctive marker that defines less severe renal involvement.

Iron, lipocalin, and kidney epithelia.

Brilliant new discoveries in the field of iron metabolism have revealed novel transmembrane iron transporters, novel hormones that regulate iron traffic, and iron's control of gene expression. An important role for iron in the embryonic kidney was first identified by Ekblom, who studied transferrin (Landschulz W and Ekblom P. J Biol Chem 260: 15580-15584, 1985; Landschulz W, Thesleff I, and Ekblom P. J Cell Biol 98: 596-601, 1984; Thesleff I, Partanen AM, Landschulz W, Trowbridge IS, and Ekblom P. Differentiation 30: 152- 158, 1985). Nevertheless, how iron traffics to developing organs remains obscure. This review discusses a member of the lipocalin superfamily, 24p3 or neutrophil gelatinase-associated lipocalcin (NGAL), which induces the formation of kidney epithelia. We review the data showing that lipocalins transport low-molecular-weight chemical signals and data indicating that 24p3/NGAL transports iron. We compare 24p3/NGAL to transferrin and a variety of other iron trafficking pathways and suggest specific roles for each in iron transport.

Chronic hyperbaric exposure activates proinflammatory mediators in humans.

Decompression illness (DCI) is an illness affecting divers subjected to reductions in ambient pressure. Besides a mechanical explanation to DCI, an inflammatory mechanism has been suggested. In this study, levels of interleukin (IL)-8, IL-6, IL-1 receptor antagonist (IL-1ra), secretory leukocyte protease inhibitor (SLPI), and neutrophil gelatinase-associated lipocalcin (NGAL) were measured in divers before and after a 2-mo period of daily diving. The divers were military conscripts and completed their diving period with no clinical symptoms of DCI. We found no change in IL-6 and IL1-ra but did find an increase in IL-8 and NGAL together with a decrease in SLPI levels. The findings suggest an inflammatory activation. This activation is not severe because no changes in IL-6 or IL-1ra were found. The increase in NGAL and IL-8 levels were interpreted as a sign of leukocyte activation. The decreased SLPI levels suggest an influence on the inflammatory defense mechanism. All in all, the findings of this study show a compensated activation of the inflammatory defense mechanism without loss of homeostasis of the inflammatory system.