Neutrophil Gelatinase-associated Lipocalin Research Articles

LCN2 regulates the gut microbiota and metabolic profile in mice infected with Mycobacterium bovis.

Our study addresses the critical knowledge gap regarding the specific influence of lipocalin 2 (LCN2) in the context of Mycobacterium bovis infection, particularly focusing on its role in the gut environment. Utilizing LCN2 knockout (Lcn2-/-) mice, we meticulously assessed changes in the gut microbiota and metabolic components following M. bovis infection. Our findings reveal alterations in the gut microbial community, emphasizing the potentially crucial role of LCN2 in maintaining stability. Furthermore, we observed significant shifts in specific microbial communities, including the enrichment of Akkermansia muciniphila, known for its positive impact on intestinal health and immune regulation. The implications of our study extend beyond understanding the dynamics of the gut microbiome, offering insights into the potential therapeutic strategies for gut-related health conditions and microbial dysbiosis.

Complex Assessment of the Functional State of the Urinary System in Preclinical Studies. Part 2. Markers of Nephrotoxicity (Review)

INTRODUCTION. The determination of nephrotoxicity markers is a useful and necessary step in the detection of renal injury in animal experiments; these markers help accurately localise organ damage. With multiple damaging agents, known nephrotoxicity mechanisms, and laboratory animal species, there is currently no widely accepted renal injury marker that meets all the prerequisites.AIM. This study aimed to collate literature data on nephrotoxicity markers, evaluate their prognostic significance, and formulate general recommendations for assessing urinary system function in preclinical studies.DISCUSSION. This article describes a comparative analysis of the nephrotoxicity markers recommended by regulatory authorities for monitoring drug-induced kidney injury. According to the results, the most commonly used and prognostically significant markers of acute kidney injury in preclinical studies are cystatin C, albumin, total protein, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin-2 (NGAL), and clusterin. Chronic kidney injury markers include the above, plus the glomerular filtration rate, creatinine, urea, and osteopontin. An electrolyte panel can be used for the differential diagnosis of pre-renal azotaemia and acute kidney injury. Potential limitations for the routine use of kidney injury markers in preclinical research include the high cost of their quantitative determination and the lack of information on the applicability of data obtained from different species of laboratory animals.CONCLUSIONS. Having compared the prognostic significance of common biomarkers, the authors provided general recommendations for a comprehensive preclinical assessment of urinary system function, including laboratory investigations, instrument-based tests, and necropsy. A preclinical study design should be based on the study aims, the species and number of animals used, and special considerations for the test article.

Value of Urine Neutrophil Gelatinase Associated Lipocalin for Prediction of Ureteropelvic Junction Obstruction in Children

Background: Congenital obstructive nephropathy is a significant cause of chronic kidney damage in childhood. Therefore, early diagnosis and management of urinary tract obstruction are necessary to prevent or reduce further renal damage. Various biomarkers have been investigated for the early identification of urinary tract obstruction. Objectives: The aim of this study was to evaluate the excretion of urine neutrophil gelatinase-associated lipocalin (Urine neutrophil gelatinase-associated lipocalin (uNGAL) & uNGAL/Cr) as a useful, sensitive, and non-invasive diagnostic biomarker in children with ureteropelvic junction obstruction (UPJO). Methods: The study cohort consisted of 47 children with obstructive UPJO and 47 healthy children with normal renal ultrasounds. Ultrasonography and 99mTc DTPA radionuclide scans were used for diagnosing UPJO. All affected children had normal renal function based on GFR measurements. Urine neutrophil gelatinase-associated lipocalin was measured using Immunoenzymatic ELISA commercial kits. Results: Urine neutrophil gelatinase-associated lipocalin & uNGAL/Cr levels were significantly higher in children with obstructive UPJO compared to the healthy control group. Additionally, both biomarkers demonstrated acceptable sensitivity and specificity for predicting for predicting UPJO. Conclusions: Based on these results, measuring uNGAL & uNGAL/Cr is suggested for evaluating children with obstructive UPJO.

Lithium-induced apoptotic cell death is not accompanied by a noticeable inflammatory response in the kidney.

Lithium (Li+) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li+ levels are nephrotoxic and can trigger a local immune response. Our understanding of the immunomodulatory effects of Li+ in the kidney is fragmentary. Here, we studied how immune mechanisms contribute to the development of Li+-induced adverse effects in the kidneys of C57BL/6NJ mice placed on a 0.3% lithium carbonate diet for 28days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR and proteome profiler arrays to characterize renal tissue damage, infiltrating immune cells and cytokine markers, activation of pyroptotic and apoptotic cascades in the kidneys of mice receiving Li+-containing and regular diets. We found that biomarkers of tubular damage, kidney injury marker, KIM-1, and neutrophil gelatinase-associated lipocalin, NGAL, were elevated in the renal tissue of Li+-treated mice when compared to controls. This correlated with increased interstitial fibrosis in Li+-treated mice. Administration of Li+ did not activate the pro-inflammatory NLRP3 inflammasome cascade but promoted apoptosis in the renal tissue. The TUNEL-positive signal and levels of pro-apoptotic proteins, Bax, cleaved caspase-3, and caspase-8, were elevated in the kidneys of Li+-treated mice. We observed a significantly higher abundance of CD93, CCL21, and fractalkine, accumulation of F4.80+ macrophages with reduced M1/M2 polarization ratio and decreased CD4+ levels in the renal tissue of Li+-treated mice when compared to controls. Therefore, after 28days of treatment, Li+-induced insult to the kidney manifests in facilitated apoptotic cell death without an evident pro-inflammatory response.

Exploring the therapeutic potential of Modafinil in mitigating renal ischemia-reperfusion injury in rats.

Renal ischemia reperfusion injury (IRI) is a post-ischemic event, which can lead to subsequent acute kidney injury (AKI), transplant failure, renal dysfunction and fibrosis via heightened oxidative stress and production of inflammatory cytokines and chemokines. This study aims to assess the effect of Modafinil, a wake-promoting agent with previously proven anti-inflammatory and anti-oxidative properties, on ameliorating renal IRI. A total of 30 male Wistar rats were divided into five groups: Sham-operated group, ischemia reperfusion (I/R) control group and Modafinil pre-treated groups (at different doses of 50, 100 and 150 mg/kg). IRI was induced by means of bilaterally clamping the renal arteries for 45 min, followed by 24 h of reperfusion. Tissue pathological assessments demonstrated a reduction of glomerular, vascular and interstitial injury at doses of 50 and 100 mg/kg of Modafinil. The biochemical studies showed a significant decrease in tissue pro-inflammatory factors, including tumor necrosis factor alpha (TNF-α), Interleukin-18 (IL-18) and lactate dehydrogenase (LDH). Moreover, an elevation was observed in levels of super oxide dismutase (SOD) and catalase, indicating the reduction of oxidative stress. Furthermore, the levels of creatinine (Cr), urea and neutrophil gelatinase-associated lipocalin (NGAL) were declined, indicating the improvement in renal function at effective doses of Modafinil (50 and 100 mg/kg) compared to the I/R control group without Modafinil pre-treatment. Our findings suggest that Modafinil holds promise as an effective therapeutic agent to address the clinical challenges associated with kidney IRI reducing the need for hospitalization and potentially alleviating related morbidities.

Advancements in Trauma-Induced Acute Kidney Injury: Diagnostic and Therapeutic Innovations.

Acute kidney injury following trauma impacts patient recovery critically, necessitating an integrated approach to emergency care and nephrology. This review aims to provide a comprehensive understanding of trauma-induced nephropathy, highlighting recent advancements in pathophysiological insights, diagnostic techniques, and strategic interventions. Our key findings emphasize the role of biomarkers, like Neutrophil Gelatinase-Associated Lipocalin and Liver Fatty Acid-Binding Protein, and imaging techniques, such as contrast-enhanced ultrasound, in early AKI detection. Preventive strategies, including aggressive fluid resuscitation, avoidance of nephrotoxic agents, and hemodynamic optimization, are essential for mitigating AKI progression. Integrating these approaches into trauma care frameworks aims to enhance patient outcomes and set a foundation for future research and clinical improvements.

Lipocalin-2 promotes breast cancer brain metastasis by enhancing tumor invasion and modulating brain microenvironment.

Breast cancer is the leading cancer diagnosed in women globally, with brain metastasis emerging as a major cause of death, particularly in human epidermal growth factor receptor 2 positive and triple-negative breast cancer subtypes. Comprehensive understanding of the molecular foundations of central nervous system metastases is imperative for the evolution of efficacious treatment strategies. Lipocalin-2 (LCN2), a secreted iron transport protein with multiple functions, has been linked to the progression of breast cancer brain metastasis (BCBM). In primary tumors, LCN2 promotes the proliferation and angiogenesis of breast cancer cells, triggers the epithelial-mesenchymal transition, interacts with matrix metalloproteinase-9, thereby facilitating the reorganization of the extracellular matrix and enhancing cancer cell invasion and migration. In brain microenvironment, LCN2 undermines the blood-brain barrier and facilitates tumor seeding in the brain by modulating the behavior of key cellular components. In summary, this review meticulously examines the fuel role of LCN2 in BCBM cascade, and investigates the potential mechanisms involved. It highlights the potential of LCN2 as both a therapeutic target and biomarker, indicating that interventions targeting LCN2 may offer improved outcomes for patients afflicted with BCBM.

A new animal model of cardiorenal syndrome could be established by inducing heart failure through coronary artery ligation in spontaneously hypertensive rats

In rats with unilateral nephrectomy and cardiac dysfunction, renal function deteriorates at an accelerated rate, as evidenced by increased proteinuria. Whether myocardial infarct-induced heart failure (HF) exacerbates renal injury in hypertensive rats with mild renal injury has not been reported. Rats underwent either coronary ligation or sham surgery. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomly divided into two groups. Group 1 was the sham group, in which the rats underwent thoracotomy without ligation of the coronary artery. Group 2 underwent coronary artery ligation. The rats in group 2 underwent coronary artery ligation on week 0. The experiment lasted 12 weeks. Urine was collected in metabolic cages over a 24-h period. Urine was collected from the rats 2 days before the end of the experiment, and the ratio of urinary protein to urinary creatinine was measured in the clinical laboratory. All rats were examined by echocardiogram one day before the end of the experiment. On the last day of the experiment, blood was collected and sent to the laboratory for analysis. Hematoxylin–eosin (HE) and periodic acid-Schiff (PAS) staining were performed on heart and kidney sections. The ejection fraction in group 2 was lower than that in group 1 (P < 0.001). The urinary albumin to creatinine ratio in group 2 was greater than that in group 1 (P < 0.001). The urea and creatinine levels in group 1 were significantly lower than those in group 2 (P < 0.01). The levels of brain natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C were greater in the second group than in the first group (P < 0.05). The interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels in group 2 were significantly greater than those in group 1 (P < 0.001). The malondialdehyde (MDA) levels in Group 2 were greater than those in Group 1 (P < 0.01). The glutathione peroxidase (GSH-Px) levels in Group 2 were lower than those in Group 1 (P < 0.05). The level of angiotensin II (AT-II) in group 1 was lower than that in group 2 (P < 0.001). Cardiac dysfunction secondary to myocardial infarction could induce cardiorenal interactions in SHRs. It could be interpreted by the activation of oxidative stress, changes in inflammation and alteration of renin–angiotensin–aldosterone system.

A Highly Sensitive Lateral-Flow Strip Using Latex Microspheres to Detect NGAL in Urine Samples.

The incidence of kidney disease is increasing worldwide. Rapid and cost-effective approaches for early detection help prevent this disease. Neutrophil gelatinase-associated lipocalin protein (NGAL) is a novel biomarker for acute kidney injury (AKI) and chronic kidney disease (CKD). We aimed to develop a lateral flow strip (LFS) based on a lateral flow immunoassay method (LFIA), using latex microspheres (LMs) as a color labeling to detect NGAL in urine. The performance and potential of the developed LMs-LFS at a point-of-care (POC) testing were evaluated. The results showed that LMs-LFS successfully detected urinary NGAL within 15 min with high specificity without cross-reactivity to or interference from other endogenous substances in urine. The visual limit of detection (vLOD) was 18.75 ng/mL, and the limit of detection (LOD) was 1.65 ng/mL under the optimum condition. The LMs-LFS developed in this study showed a high correlation with the enzyme-linked immunosorbent assay (ELISA) method (R 2 = 0.973, n = 60 urine specimens) for detecting NGAL in urine. The LMs-LFS remained stable for at least six months at room temperature. The LMs-LFS can be a rapid, sensitive, and specific tool for the diagnosis and follow-up of renal disorders at the POC.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Copper-loaded ZIF-8-based immunosensor for early diagnosis of chronic kidney disease by detecting neutrophil gelatinase-associated lipocalin (NGAL) biomarker

Metal-organic frameworks (MOFs) is a promising contender among the nanomaterials for biosensors due to their special properties, including high surface area, tunable porosity, and adaptable functionalization competences. Zeolitic imidazolate frameworks (ZIFs), a subclass of MOFs, have drawn precise attention for their excellent chemical stability and ease of synthesis. This study, for the first time, concentrates on the preparation and characterization of a Cu-loaded ZIF-8-based immunosensor for the detection of neutrophil gelatinase-associated lipocalin (NGAL), a crucial biomarker for chronic kidney disease (CKD). Loading copper (Cu) into the ZIF-8 framework improves its electrochemical properties, conductivity, and surface area, leading it an ideal platform for antibody immobilization and NGAL detection. The immunosensor utilized Staphylococcal Protein A (SPA) IgG binding protein for antibody immobilization, providing an alternative to traditional crosslinking chemistry, enhancing biosensor functionality. Structural analysis, morphological assessment, elemental mapping, and stoichiometric analysis confirmed the successful synthesis of Cu-loaded ZIF-8 nanocomposite. Assessment of the electrochemical performance of the immunosensor demonstrated sufficiently low limit of detection (80 pg mL−1) over a wide range of 0.1 ng mL−1 to 1000 ng mL−1 of NGAL along with superior selectivity, reproducibility, stability, and clinical feasibility. This advancement contributes to the rising knowledge on MOF-based biosensors and holds promise for future applications in disease diagnosis and healthcare monitoring.

Electrochemical Detection of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Simulated Urine Using Au@Si/Ni-Porphyrin Nanocomposite for the Prediction of Kidney Injury

Kidney Injury is multifactorial out of which ureteropelvic junction obstruction is one of the major causes of concern. There are a multitude of methods for monitoring the deterioration of renal function like serum creatinine levels, ultrasound scans, renograms, and nuclear scans like radiolabelled MAG3 and DMSA which require repeat evaluation or sedation during the process. Many of the biomarkers utilized for the assessment of kidney injury are expressed at the later stages. Urine NGAL is a promising biomarker for risk stratification which is reported to be expressed at the onset of ureteropelvic junction obstruction (UPJO) and is a gold standard for the estimation of tubular injury. Urinary NGAL is also reported to be a specific marker for the prediction of hydronephrosis in children who require surgical intervention. The kidney injury cut-off for NGAL in urine is 185ng/mL and 48 ng/mL in the adult and pediatric population groups respectively. Electrochemical detection of NGAL in patient urine is a fast, reliable, non-invasive, accurate, and cost-effective method for monitoring kidney health to segregate patient groups that require surgical intervention.In this study, an electrochemical sensor was designed with Au(150nm) electrodes fabricated using thermal evaporation on a flexible substrate (PET; 250μm) by using Cr(20nm) as the seed layer. The electrode was immobilized with Au@Si core-shell decorated on Ni-porphyrin nanosheets functionalized with anti-NGAL using covalent chemistry. The nanocomposite was synthesized through a bottom-up approach where the Ni-tetrakis(4-carboxyphenyl) porphyrin nanosheets were synthesized using the solvothermal method in an organic phase (DMF) followed by purification and suspension in ethanol medium. The Si nanocrystals were synthesized in a citrate medium with APTMS as the precursor followed by purification via dialysis. The purified Si nanocrystals (60ppm) and Ni-porphyrin nanosheets (880ppm) were treated in chloroauric acid (0.25mM) and the reducing agent trisodium citrate (34mM) to form Au shell. The physicochemical and electronic properties of the synthesized nanocomposite were evaluated through XRD, XPS, microscopic analysis(TEM, SEM), AFM, UV-Vis, FTIR, and Raman spectroscopy. The resultant nanocomposite was purified and linked to anti-NGAL (100μg/mL) through EDC (0.4M)/NHS (0.1M) chemistry. The antibody-nanocomposite was immobilized on the fabricated Au electrodes (working electrode surface area: 0.35mm2) through BSA(1.2mM)/glutaraldehyde (2.5% v/v) crosslinking. The quantitative electrochemical estimation of NGAL antigen spiked in 0.1M PBS (pH=7.2±0.2) and simulated urine was performed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The shelf life of the fabricated sensors was evaluated for 30 days (stored at 4˚ C until use) over the concentration range of 0-5000 ng/mL. The amount of test solution required per measurement for the miniaturized electrodes was 6μL.The sensing mechanism of the electrochemical platform was established through CV by varying the scan rate (0.05 V/s - 2.5 V/s) for 500ng/mL in 0.1M PBS and urine. With increasing scan rate a linear relationship between log ip and log ν was observed. For 0.1M PBS, the process was largely capacitive at various detected potentials (b=0.94 @ 0.5V; b=0.86 @ 0.3V; b=0.85 @ 0.07V). However, in the case of simulated urine, the electrochemical process was diffusion-limited at 0.6V (b=0.49). Therefore, to obtain higher current sensitivity in the diffusion-limited regime, DPV was adopted. With increasing concentration of antigen NGAL, a monotonic decrease in the redox current at 0.6V and 0.45V potential was observed. This signifies that the presence of NGAL antigen leads to the formation of antigen-antibody complex immobilized on the surface of the nanocomposite translating into an increase in the resistance at the electrode surface leading to a decrease in the redox current. The decrease in the current was proportional to the increase in the amount of the test antigen. The sensitivity of the sensor at 0.45V and 0.6V was 2.22 nA/ng mL-1/mm2 and 0.51 nA/ng mL-1/mm2 respectively with the lowest limit of NGAL detection as 12.5ng/mL in simulated urine by using DPV. Similarly, for CV the sensitivity of the sensor at 0.56V was 3.48 nA/ng mL-1/mm2 with 22ng/mL as the limit of detection. The sensor performance was evaluated without the use of nanocomposite (only antibody) as a control for comparison.Therefore, this study is a proof of concept for an effective electrochemical sensor platform design for urinary NGAL detection using a novel nanocomposite. It was established that the use of nanocomposite provides a better surface area to volume ratio through the core-shell nanostructures decorated on the nanosheets translating into higher electrochemical activity. The sensing platform was found to be specific, sensitive, and stable making it a perfect candidate for a point-of-care-testing(POCT) platform. Figure 1

Serum and urinary biomarkers of vancomycin-induced acute kidney injury: A prospective, observational analysis.

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (μg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Early Detection of Chronic Kidney Disease Using Plasma Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Small-Breed Dogs: A Retrospective Pilot Study.

Multiple diagnostic modalities are urgently needed to identify early-stage kidney diseases. Various molecules have been investigated; however, most studies have focused on identifying specific biomarkers in urine. Considering that assessing the symmetrical dimethylarginine (SDMA) plasma concentration is more suitable as an early diagnostic test for chronic kidney disease (CKD) in routine veterinary practice, we aimed to investigate the clinical usefulness of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) concentrations for CKD detection in small-breed dogs. Through a retrospective analysis, we found that numerous clinicopathological data showed a log-normal distribution, even when they satisfied normality tests. Moreover, the log-transformed pNGAL and pKIM-1 concentrations successfully identified CKD International Renal Interest Society (IRIS) stages 1-4 and the risk group with underlying CKD risk factors. Correlation analysis and group comparison of other factors confirmed the possibility of using these two biomarkers for detecting the CKD risk group and IRIS stage 1. Receiver operating characteristic curve analysis revealed that the diagnostic accuracy for discriminating the risk group was superior in the order of pKIM-1, pNGAL, SDMA, and serum creatinine levels. In conclusion, these results suggest that pKIM-1 and pNGAL are possible early or quantifiable markers of insignificant CKD or can be at least used as an adjunct with traditional indicators.

Biomarkers of oxidative stress and inflammation in contrast-associated acute kidney injury

Iodinated contrast-induced acute kidney injury (CI-AKI) is a common cause of renal failure, especially in patients with risk factors. This study analyses different renal biomarkers in patients undergoing computed tomography scans with iodinated contrast to identify the molecular and cellular mechanisms involved in the pathogenesis of CI-AKI. Prospective study that included patients with high risk of renal disease who received iodinated contrast (iohexol) for the computed tomography scans. Functional biomarkers (creatinine and cystatin C), inflammatory and oxidative stress markers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-8 [IL-8], superoxide dismutase [SOD], F2-isoprostanes, and cardiotrophin-1), and cell cycle biomarkers (Nephrocheck®) were analysed before the iodinated contrast and 4, 12, 24, and 48 hours post-contrast, in relation to the incidence of IC-AKI. IC-AKI was observed in 30.6% of the 62 study participants and in 57.1% of the patients with diabetes and renal dysfunction. Factors associated with IC-AKI were a higher mean age (74.4 vs 64.9 years), pre-existing renal dysfunction (60 vs 16.7%), and higher adjusted mean volume of iohexol (42.9 vs 32.1%). As for non-functional biomarkers. No differences were found between patients with and without CI-AKI. The use of iodinated contrast was associated with a decrease in SOD antioxidant activity at 4 hours and an increase in IL-8 at 12 hours post-administration of the iodinated contrast. Administration of iohexol in computed tomography scans in patients with high risk of renal disease results in an elevated percentage of CI-AKI, attributable to ischemia/reperfusion injury and/or direct toxicity of the iodinated contrast.

Urine dipstick blood and acute kidney injury in infants undergoing cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with hemolysis and acute kidney injury (AKI). The study aim was to determine if urine dipstick blood in infants after CPB was associated with AKI and urine neutrophil gelatinase-associated lipocalin (NGAL). Infants who underwent CPB at a single center were enrolled prospectively between October 2017 and June 2019. Urine samples prior to CPB and 6h after CPB cessation were analyzed in batch for NGAL and dipstick blood. AKI was defined using creatinine-based KDIGO criteria within 72h of CPB. Spearman correlation examined associations between urine dipstick blood and NGAL at each time point. Linear regression estimated the associations between urine dipstick blood and log-transformed NGAL 6h after CPB. Logistic regression estimated associations and compared discrimination between urine dipstick blood and NGAL for predicting AKI. At baseline, 7/63 samples (11%) had > trace blood. Six hours after CPB, 62/98 samples (63%) had > trace blood and 26% had 3 + (large) blood. In total, 18/98 (18%) with a 6-h post-CPB sample had postoperative AKI. Urine dipstick blood values correlated with urine NGAL 6h after CPB (r = 0.52, p < 0.01), but not at baseline (r = 0.06, p = 0.66). Those with 3 + (large) blood on urine dipstick had 6 times higher mean NGAL values compared to those with negative/trace blood (mean ratio 6.6, 95%CI 3.1-14.4, p < 0.01). Those with 3 + (large) blood had 8 times higher odds of AKI (OR 7.99, 95%CI 1.5-41.9, p = 0.01). Urine dipstick blood post CPB may be a simple and inexpensive tool to help predict AKI in infants.

A novel pharmacological strategy using nanoparticles with glutathione and virgin coconut oil to treat gentamicin-induced acute renal failure in rats.

In acute renal failure (ARF), the glomerular filtration rate is reduced, and nitrogenous waste products accumulate persistently, which can last anywhere from a few hours to several days. There is hope for a reversal of the rapid loss of renal function caused by this condition. This study, with gentamicin-induced acute ARF as a prospective setting, sets out to examine the reno-protective benefits of virgin coconut oil (VCO) and GSH. Furthermore, the study evaluated the effect of medication nanoparticle compositions on several kidney function markers. The induction of ARF is achieved with the intraperitoneal injection of gentamicin. To assess renal function, rats underwent 24h of dehydration and hunger before their deaths. The study examined various aspects, including kidney function tests, markers of oxidative stress, histology of kidney tissue, inflammatory cytokines, immunohistochemistry expression of nuclear factor-kappa B (NF-κB), and specific biomarkers for kidney tissue damage, such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). The results of our study indicated that the combination of VCO and GSH, using both regular and nanoparticle formulations, had a better protective impact on the kidneys compared to using either drug alone. The recovery of renal tissue and serum markers, which are symptomatic of organ damage, indicates improvement. This was also demonstrated by the reduction in tubular expression of TNF-α, IL-1β, KIM-1, and NGAL. The immunohistochemical studies showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of NF-κB. The study shows that VCO and GSH, when administered individually or combined, significantly improve ARF in a gentamicin-induced rat model, highlighting potential therapeutic implications. Notably, the combined nanoparticulate formulations exhibit substantial effectiveness.

The diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in assessing kidney function in severe hydronephrosis.

Up to now, there is no perfect indicator to evaluate the renal function of severe hydronephrosis, which poses difficulties in the selection of clinical treatment decisions. This study investigates the role of neutrophil gelatinase-associated lipocalin (NGAL) in urine drained from the nephrostomy tube shortly after nephrostomy to evaluate the renal function of patients with severe hydronephrosis caused by ureteral obstruction. The clinical data, and blood and urine samples of 24 patients with severe hydronephrosis due to ureteral obstruction were retrospectively collected. The NGAL in the urine drained from the nephrostomy tube on the morning of the first day after the procedure was measured. The glomerular filtration rate (GFR) was determined using a nuclear scan, and the clearance rate of creatinine was calculated based on nephrostomy drainage. The correlation between the NGAL level, urine volume post-nephrostomy, affected side GFR, and creatinine clearance rate (Ccr) was assessed. Moreover, the relationship between the urinary NGAL levels and prognosis was analyzed based on whether the patients underwent nephrectomy. There was a significant correlation between the urine NGAL from the nephrostomy of the affected side and the Ccr and urine volume post-nephrostomy (both P<0.05). Compared with the patients in the kidney preservation group, those who underwent nephrectomy had significantly increased NGAL levels, and significantly reduced Ccrs and nephrostomy drainage urine output. Through the receiver operating characteristic (ROC) curve evaluation, the efficacy of NGAL in predicting nephrectomy was found to be superior to both the Ccr and urine output, with an area under the curve (AUC) of 0.845. The NGAL in the urine shortly after nephrostomy may indicate severe renal functional deterioration.

HIF-1α Pathway Orchestration by LCN2: A Key Player in Hypoxia-Mediated Colitis Exacerbation.

In this study, we investigated the role of hypoxia in the development of chronic inflammatory bowel disease (IBD), focusing on its impact on the HIF-1α signaling pathway through the upregulation of lipocalin 2 (LCN2). Using a murine model of colitis induced by sodium dextran sulfate (DSS) under hypoxic conditions, transcriptome sequencing revealed LCN2 as a key gene involved in hypoxia-mediated exacerbation of colitis. Bioinformatics analysis highlighted the involvement of crucial pathways, including HIF-1α and glycolysis, in the inflammatory process. Immune infiltration analysis demonstrated the polarization of M1 macrophages in response to hypoxic stimulation. In vitro studies using RAW264.7 cells further elucidated the exacerbation of inflammation and its impact on M1 macrophage polarization under hypoxic conditions. LCN2 knockout cells reversed hypoxia-induced inflammatory responses, and the HIF-1α pathway activator dimethyloxaloylglycine (DMOG) confirmed LCN2's role in mediating inflammation via the HIF-1α-induced glycolysis pathway. In a DSS-induced colitis mouse model, oral administration of LCN2-silencing lentivirus and DMOG under hypoxic conditions validated the exacerbation of colitis. Evaluation of colonic tissues revealed altered macrophage polarization, increased levels of inflammatory factors, and activation of the HIF-1α and glycolysis pathways. In conclusion, our findings suggest that hypoxia exacerbates colitis by modulating the HIF-1α pathway through LCN2, influencing M1 macrophage polarization in glycolysis. This study contributes to a better understanding of the mechanisms underlying IBD, providing potential therapeutic targets for intervention.

Development and Validation of a Nomogram for Predicting Acute Kidney Injury in Septic Patients.

Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients. We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital. 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825-0.921) and 0.826 (95% CI 0.727-0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value. The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.