Urinary Neutrophil Gelatinase-associated Lipocalin Research Articles (Page 1)

Regulating the GTP cyclohydrolase 1/tetrahydrobiopterin axis in the distal tubule inhibits ferroptosis and alleviates crush syndrome-related acute kidney injury in mice.

In patients with chronic kidney disease (CKD), the presence of concomitant atrial fibrillation (AF) increases both the risk of thromboembolic complications and the risk of bleeding associated with the use of antithrombotic drugs. The risk of these complications is especially high in elderly and senile individuals. Currently, a number of markers of kidney damage have been identified, but the relationship between the level of their excretion in urine and the presence of bleeding in patients with CKD and AF receiving anticoagulants has not been sufficiently studied. The aim of this study was to evaluate the possible relationship between the presence of bleeding in patients with CKD stages C3–4 and AF receiving rivaroxaban and the level of renal damage markers in urine. The study included 266 patients aged 65-97 years: 140 patients with AF and CKD C3a and 126 patients with AF in combination with CKD C3b and C4. Patients took rivaroxaban at a dosage of 15 mg or 20 mg once a day, depending on the glomerular filtration rate. All patients underwent a retrospective assessment of the presence of bleeding according to the HAS-BLED scale, analysis of the excretion of markers of renal injury (albumin; nephrin; neutrophil gelatinase-associated lipocalin (NGAL); kidney injury molecule-1 (KIM-1)) with urine. Additionally, an analysis of the level of markers of renal damage in the urine of 90 healthy volunteers was performed. According to the risk of bleeding, patients were divided into 2 groups: Group 1 included patients with ≥1 point (92 patients), average age 80.7 years). Group 2 included patients with 0 points: 174 patients, average age 78.2 years. Of the bleeding, bruises were common in 52 patients (19%), nosebleeds were found in 22 patients (8.3%), bleeding from minor wounds was noted in 12 patients (4.3%), muscle hematomas were found in 6 patients (2.2%), bleeding from the oral cavity was found in 6 patients (2.2%), and hemorrhoidal bleeding was diagnosed in 2 patients (0.75%). The levels of NGAL and KIM-1 in urine in patients with AF and CKD in group 1 (5.6 ng/ml and 0.69 ng/ml, respectively) were statistically significantly higher compared to patients in group 2 (4.2 ng/ml (p=0.039) and 0.39 ng/ml (p=0.019, Table 1). Our study results indicate the presence of a statistically significant association between the presence of bleeding in patients with AF and CKD stages 3–4 receiving rivaroxaban with the level of tubular damage markers KIM-1 and NGAL in urine.

Kidney injury is one of the most serious health problems, including drug-induced acute kidney injury (AKI) and disease-induced chronic kidney disease. Neutrophil gelatinase-associated lipocalin (NGAL) carried by urinary exosomes (uExos) has emerged as a potential biomarker for the diagnosis of kidney injury. However, sensitive detection of urinary exosomal NGAL remains challenging due to its low abundance in urine during the early stages of kidney injury. In this study, we developed a highly sensitive uExos analysis platform by integrating deoxyribonuclease I (DNase I)-mediated biomarker cycling with a metal-enhanced fluorescence (MEF) effect for dual fluorescence signal amplification. This method achieved a remarkably low limit of detection (LOD) of 3.02 × 103 particles/mL, with a linear range from 5 × 103 to 2 × 1011 particles/mL. Using this approach, we successfully distinguished urine samples from diabetic nephropathy (DN) patients and healthy donors (HD) by analyzing the level of urinary exosomal NGAL. Moreover, in a rat model of cisplatin-induced AKI, our strategy detected abnormalities as early as 12 h postcisplatin injection─significantly earlier than conventional clinical biomarkers such as serum creatinine (sCr) and blood urea nitrogen (BUN). Additionally, this method demonstrated the potential for accurately evaluating the efficacy of anti-AKI therapeutics. In summary, the dual signal amplification strategy presented in this study facilitates early diagnosis of both chronic and acute kidney injury while offering a powerful tool for dynamically monitoring therapeutic responses in kidney disease.

Abstract Background and Aims Differentiating functional acute kidney injury (AKI) from structural tubular injury AKI remains challenging with existing clinical tools. urinary NGAL (uNGAL) has shown promise in distinguishing functional AKI, such as “Pre-Renal” AKI, from tubular injury (“Intra-Renal”) AKI. We evaluated the implementation of uNGAL in the clinical nephrology consult service over 3-year period in a heterogenous medical AKI population at a single center in Ireland. Method A retrospective audit investigating the clinical utility of uNGAL in an adult population at an Irish hospital was conducted from 2020–2023. Standard clinical data, such as clinical history, examination findings, radiology reports, serial serum creatinine and urea levels, proteinuria, FENa, and infection status around the time of AKI and uNGAL request were recorded. Blinded adjudication of the standard clinical data was performed between two expert Nephrologists. Responses were limited to: “Pre-Renal”, “Intra-Renal”, “Post-Renal”, “No-AKI”, or “Not Enough Information”. uNGAL accuracy in differentiating Intrinsic AKI from Functional AKI (Pre-renal & Post-renal) was assessed, and box plots visualized uNGAL and FENa levels across groups. Results A total of 320 uNGAL tests were performed between 2020 and 2023, which 292 were adjudicated to their AKI case. Adjudicated intra-renal AKI patients (n = 120) demonstrated significantly higher raw uNGAL levels (median: 1052 ng/ml [IQR: 302.4–1314.4]) compared to functional (median: 228.2 ng/ml [IQR: 69.7–895.1; P = 2.00 × 10-9) (Table 1). Similarly, cr-corrected uNGAL levels were significantly higher (P = 8.20 × 10⁻¹¹) in the intrinsic group (median: 1288.7 ng/mg [IQR: 438.2–2317.2]) compared to the functional group (median: 323.7 ng/mg [IQR: 86.9–1083.7]). These differences remained significant after adjusting for UTI status (Raw uNGAL: P = 1.34 × 10⁻¹²).; cr-corrected uNGAL: P = 5.66 × 10⁻¹²). The diagnostic accuracy of raw uNGAL at the manufacturer-recommended threshold of 150 ng/ml for adjudicated intrinsic AKI was moderate, with an AUC of 0.71 (95% CI: 0.64–0.77). At a lower threshold of 125 ng/ml, a similar diagnostic performance was observed. Cr-corrected uNGAL demonstrated slightly better performance, with an AUC of 0.73 (95% CI: 0.67–0.79) at a threshold of 150 ng/mg. FENa, in comparison, showed moderate diagnostic accuracy at a threshold of 2% (AUC: 0.67 [95% CI: 0.67–0.75]), with higher specificity (0.73) but lower sensitivity (0.47). After controlling for UTI status, the diagnostic accuracy of both raw and cr-corrected uNGAL improved. The AUC for raw uNGAL increased to 0.77 (95% CI: 0.71–0.84), while cr-corrected uNGAL improved to 0.76 (95% CI: 0.70–0.83). Sensitivity remained high for both raw uNGAL (0.87 to 0.86) and cr-corrected uNGAL (0.92 to 0.90), with NPV remaining stable (0.82 to 0.82 for raw uNGAL; 0.87 to 0.85 for cr-corrected uNGAL). Conclusion The use of uNGAL, raw or cr-corrected, improved the accuracy of differential diagnosis of AKI in clinical practice by differentiating intrinsic AKI from functional. Specificity was lower at the recommended manufacturer (150 ng/ml) and pediatric (125 ng/ml), but the sensitivity and NPV was high therefore supporting the use to rule-out an intrinsic injury clinically. The presence of UTI does not consistently result in an increase in uNGAL levels.

Abstract Background and Aims Acute heart failure (AHF) patients treated with diuretics often develop worsening of renal functions with resultant acute kidney injury (AKI) during hospitalization. This AKI could be a result of either renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Method 100 AHF patients who underwent aggressive diuresis were included (excluding patients requiring inotropic support or haemodialysis). Urine NGAL was measured on the day of admission and after 72 hours. Serum creatinine levels were measured on day of admission, at 48 hours and at 72 hours post admission. AKI was defined as per KDIGO clinical practice guidelines as increase in serum creatinine by 0.3 mg/dL or more within 48 hours or urine output less than 0.5 mL/kg/h for 6 hours. All patients were contacted at 30 days from the day of admission and reviewed regarding requirement of readmission/mortality. All patients who developed AKI during the study by day 3 got their creatinine checked again at day 30 from the day of admission. Results Mean eGFR of patients was 48.1 ml/min/m2. Mean NT-proBNP was 11000 pg/ml. Mean LVEF was 43.65%, with 38% patients having HFrEF and 62% patients had HFpEF (LVEF >40%). Of total 100 patients, 37 (37%) developed AKI. Rise in NGAL from day 0 to day 3 was noted in 34 (34%) cases. There was no correlation found between rising creatinine levels and rising NGAL levels (including patients with AKI). Mean NT-proBNP was higher in patients with AKI as compared to those without AKI (p-value = 0.048). Of 37 AKI patients, 10 (27%) patients had creatinine value at day 30 higher than at day 3, while 27 (73%) patients had creatinine value at day 30 lower than at day 3. 30 patients required readmission within 30 days after discharge; 5 patients expired by day 30 (from start of study). Occurrence of AKI did not show association with readmission within 30 days or with mortality at 30 days. Conclusion AKI occurred in 37% patients with AHF undergoing aggressive diuresis in our study (Table 20, Fig. 18). This AKI had no correlation with serial NGAL levels (tubular injury biomarker) but was associated with an elevated baseline NT-proBNP levels (Table 21, Fig. 19). Furthermore, 73% AKI patients showed improvement in creatinine levels by day 30 post discharge (Table 25, Fig. 23) & occurrence of AKI did not affect short term morbidity (readmission at 30 days) and mortality at 30 days (Table 26, Fig. 24). This implies that AKI in the setting of AHF & aggressive diuresis is mild, mainly functional/hemodynamic and should not affect decisions with decongestive therapy.

Abstract Background and Aims Nephrotoxicity associated with immune checkpoint inhibitors (ICIs), although less common than other complications, worsens the patient's prognosis. On the other hand, the diagnosis based on plasma creatinine has limitations. The aim of this study was to investigate the role of urinary biomarkers in the diagnosis of ICI-induced kidney damage. Method This study was carried out following a previously published protocol [1]. Patient recruitment was carried out in two Medical Oncology Services. Their urine samples were analysed, before the start of treatment and in cycle 3 both before and one week after administration, for the biomarkers albumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG) and insulin-like growth factor-binding protein 7 (IGFBP-7), by ELISA and colorimetric techniques. The patients were classified into Controls (patients without alterations in kidney damage, in at least twelve cycles) and Cases (patients with kidney damage evidenced by an increase in plasma creatinine, a decrease in the glomerular filtration rate or electrolyte alterations compatible with ICIs treatment). Results A significant increase in excretion of albumin and NGAL was observed in Cases before receiving the third cycle, indicating early renal damage associated with ICIs. These could predict kidney injury that becomes evident over time. On the other hand, KIM-1, NAG and IGFBP-7 showed greater excretion in Cases even before receiving therapy, therefore these biomarkers would allow identifying patients with a higher risk of kidney damage and managing them clinically before administering therapy. Conclusion These results are an open door to a larger study that could confirm the clinical application of the urinary biomarkers albumin, NGAL, KIM-1, NAG and IGFBP-7 in the diagnosis and management of kidney damage due to ICIs.

Abstract Background and Aims Acute kidney injury (AKI) is a common syndrome in hospitalized patients worldwide and is associated with progression to chronic kidney disease (CKD). Proximal tubule epithelial cells (PTECs) are highly susceptible to injury in AKI resulting in proliferation, which is suggested to be important for tubule recovery and prevention of CKD progression. Roxadustat, a hypoxia-inducible factor (HIF) stabilizer, is a novel drug for the treatment of CKD-related anemia. Some studies have reported the protective effect of Roxadustat on animal AKI models. However, it remains unclear whether Roxadustat induces proliferation and is associated with recovery of renal tubules. Here, we evaluated the effect of Roxadustat on proliferation of PTECs in vitro and in glycerol-induced AKI mice. Method Male C57BL/6J mice were randomly divided into four groups (n = 5–11): a control (i) and a glycerol (Gly) (ii) group received intramuscular injections of PBS or 50% glycerol (5 ml/kg) and a PBS+Rox (iii) and a Gly+Rox (iv) group received intraperitoneal injection of Roxadustat 10 mg/kg/day 2 days prior to glycerol or PBS injection. Urine, kidneys, and blood samples were collected 2 days after glycerol injection and renal dysfunction was evaluated (serum urea nitrogen and creatinine) as well as tubular damage (PAS staining, renal NGAL and Kim-1 expression, and urine NGAL excretion). Renal expression of PCNA, a proliferation marker, was determined by western blotting and immunohistochemistry. PTECs proliferation was analyzed in immortalized proximal tubular cells (RPTEC/TERT1, ATCC) treated with roxadustat by a CCK-8 assay, a wound-healing assay, and western blotting (Ki-67, cyclin A, and phosphorylated Rb). Results Roxadustat treatment significantly suppressed AKI markers (renal NGAL and Kim-1 expression and urine NGAL excretion) and tubular injury score (PAS staining) in glycerol-injected AKI mice. Additionally, Roxadustat treatment reduced serum urea nitrogen and creatinine levels in glycerol injected mice suggesting that it protects proximal tubules against injury, which leads to rescue of renal function. To investigate if the renoprotective effect of Roxadustat was mediated by stimulation of proliferation PCNA-positive PTECs were analyzed. Glycerol injected mice had an increase in PCNA positive cells compared to PBS treated mice as expected. The Gly+Rox group had the same level of PCNA positive PTEC cells as the Gly group despite less renal damage. These results indicate that there may be either a direct proliferative effect of Roxadustat or that the treatment by other mechanisms protect the kidney resulting in less proliferation. To investigate if there is a direct effect of Roxadustat on proliferation we analyzed Roxadustat treatment in RPTEC/TERT1 cells. Roxadustat treatment significantly induced the increase in HIF-1α protein in RPTEC/TERT1 cells. CCK-8 and wound-healing assays revealed that Roxadustat-treated cells showed significant increase in cell proliferation, which was supported by western blotting of Ki-67, cyclin A, and phosphorylated Rb. Furthermore, HIF-1α-knockdown by small interfering RNA tended to suppress the expression of proliferation markers. Conclusion The present study indicates that HIF-1α activation by Roxadustat treatment accelerates cell proliferation in PTECs as a part of the protective mechanism of Roxadustat on tubule damage and AKI.

Acute kidney injury (AKI) occurs in 30% of premature neonates and is associated with adverse outcomes that may be mitigated with early detection. Diagnosis of AKI relies on serum creatinine (SCr) which has several limitations, including lack of sensitivity and specificity. There are limited data on the utility of alternative urine biomarkers to predict AKI in neonates born at < 25weeks' gestation. Urine was collected from neonates born at < 25weeks' gestation during the first postnatal week. Two urine AKI biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and epidermal growth factor (EGF) were measured. Study participants were prospectively followed to determine development of AKI, defined by the neonatal modified Kidney Disease-Improving Global Outcomes (KDIGO) criteria, during the first postnatal week. The association of NGAL and EGF with AKI was analyzed using mixed-effect linear regression models adjusting for gestational age at birth. A total of 26 neonates were enrolled in this study. After adjusting for gestational age at birth, the mean difference in log-transformed biomarkers at three time points for urine NGAL and EGF was not statistically different between cases and controls. Although the urinary biomarkers studied were not associated with diagnosis of AKI, AKI was associated with lower birth weight (p = 0.02). This study provides preliminary information about urine NGAL and EGF in neonates < 25weeks' gestation, a growing patient population at high risk for kidney injury. The relationship between urinary biomarkers and outcomes in this population warrants further investigation.

Abstract Background Acute kidney injury (AKI) is commonplace after surgery and is correlated with a higher risk of morbidity, mortality and economic burden. Identifying early onset AKI is crucial in managing patients, improving outcomes thereby reducing economic burden to all. Creatinine is widely utilized for detecting AKI. However, its elevation is delayed post kidney injury. The biomarkers kidney injury molecule (KIM-1) and neutrophil gelatinase associated lipocalin (NGAL) have been evaluated as early AKI predictors with promising results. This prospective pilot study aims to address the data deficit by evaluating these biomarkers as early predictors of AKI in a subset of patients undergoing cardiopulmonary bypass (CPB) surgery. We theorize that NGAL and KIM-1 will be good markers of early AKI post cardiac surgery. Methods This study was conducted within a year at The University Hospital of the West Indies with 18 patients available for consent. Urine and serum samples were collected pre-operatively, 2 hrs, 4hrs and 24hrs post-surgery for evaluation. Urine KIM-1 and NGAL concentrations were determined using ELISA kits (Elabscience). Serum creatinine concentration was assessed on the Cobas analyzer. Independent sample t-tests and Pearsons’s chi-square tests were performed to analyze the biomarkers, peri-operative and demographic data obtained. ROC curves assessed the diagnostic performance of the biomarker tests and for those that were significant, a cutoff value for that biomarker was determined with its associated sensitivity and specificity. Statistical analyses were performed using SPSS version 28 Results Two patients died peri-operatively, while four patients developed AKI. Prolonged CPB and aortic cross clamped times were significant risk factors for developing AKI. AKI was associated with a longer hospital stay. NGAL was an excellent predictive biomarker for AKI 2hrs post-surgery where the AUC for receiver operating characteristics was 0.925, p=0.016, 95% CI with a sensitivity of 0.75 and specificity of 1.00, at a cut off value of 165.76 ng/ml. NGAL was also found to be useful in detecting AKI severity (defined by KDIGO guidelines 2012). There was an early rise in the mean serum creatinine level, from 94.75 µmol/L pre-operatively to146.75 µmol/L, 2hrs post operatively. The AUC for creatinine at 4hrs after surgery was 0.938, p=0.011 with a cutoff of 107.50µmol/L at a sensitivity of 1.000 and specificity 0.833. The AUC for creatinine at 24hrs was 0.958, p=0.008 with a sensitivity and specificity of 1.00 and 0.917 respectively, at a cutoff value of 120.50 µmol/L. KIM-1 was not statistically significant for detecting AKI. Conclusion This study demonstrated the need for a similar large-scale study and the potential of urine NGAL to be a superior predictive biomarker for detecting AKI at 2hrs after CPB surgery. Urine NGAL was useful in detecting the severity of AKI. KIM-1 was not statistically significant in predicting early AKI. Serum creatinine concentration increased early in AKI patients at 2hrs post-surgery and was excellent at discriminating AKI and non-AKI patients at 4hrs and 24hrs post-surgery. Recommendations to improve early diagnosis of AKI include testing NGAL at 2hrs after CPB surgery and serum creatinine early after surgery.

The prediction of rapid progression in diabetic kidney disease (DKD) remains a global challenge. This study evaluated the prognostic value of two noninvasive biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1) in identifying rapid DKD progression. In this prospective observational study, 145 T2DM patients with DKD (October 2021–June 2024) were categorized as rapid or nonrapid progressors based on an eGFR decline >5 mL/1.73 m2/year. Baseline urinary(u) NGAL and MCP-1 were measured by ELISA. Clinical profiles, risk factors, and predictive utility of the biomarkers were analyzed. During a median follow-up of 1.3 years, 38.6% were rapid progressors. Hypertension, cardiovascular disease, elevated SBP, high fasting blood sugar, and higher urinary albumin-to-creatinine ratio (uACR) were significantly associated with rapid progression (p < 0.05). Median uNGAL and uMCP-1 levels were higher in rapid progressors (57.6 vs 28.2 ng/ml; 469 vs 220 pg/ml; p = 0.01) and increased with albuminuria severity (p = 0.03 and p = 0.01). Multivariate analysis identified uNGAL, uMCP-1, and uACR as independent risk factors. uMCP-1 showed the highest diagnostic accuracy (AUC 0.94; 94.1% sensitivity; 89.2% specificity at 381.2 pg/ml). uNGAL had an AUC of 0.86 (83.4% sensitivity; 77.3% specificity at 39.8 ng/ml). A combined panel of uMCP-1, uNGAL, and uACR further improved predictability (AUC 0.96). Patients with elevated uNGAL and uMCP-1 levels experienced a greater incidence of rapid progression similar to uACR. uMCP-1 exhibited better diagnostic accuracy than did uNGAL and uACR, with better sensitivity and specificity in identifying rapid progressors. The combination of three noninvasive biomarkers had further improved predictability.

Dihydroartemisinin (DHA) is a potential therapeutic strategy in multiple diseases, but its effects on Diabetic nephropathy (DN) have been not explored yet. Rats underwent unilateral ureteral obstruction surgery and injected by streptozotocin to induce DN, with treatment by DHA (15 and 30mg/kg), and Losartan was used as a positive control. Blood glucose, and 24-h urine protein and glucose tolerance were detected to ensure kidney function. Periodic acid Schiff, hematoxylin and eosin and Masson staining were conducted to assess histological changes. Western blot and immunofluorescence were used for examining protein expression. HK-2 cells were subjected to high glucose (HG) exposure. Flow cytometry and Cell counting kit-8 were applied for assessing cell apoptosis and viability. Mitochondrial membrane potential (MMP), ATP production and respiratory chain complex activity were detected to assess mitochondrial function. DHA significantly improved renal functions of DN rats by reducing blood glucose and urine protein levels, inhibiting Kim-1 and NGAL expression and alleviated pathological damage dose-dependently. DHA relieved tubulointerstitial fibrosis through hindering epithelial-mesenchymal transition and ECM deposition, and attenuated mitochondrial dysfunction. In vitro experiments revealed that DHA ameliorated HG-caused ROS production, apoptosis and upregulation of HIF-1α/HO-1 in HK-2 cells. DHA might promote the degradation of HIF-1α via enhancing its ubiquitination, and HIF-1α/HO-1 was implicated with the suppressive effect of DHA on mitochondrial apoptosis in HG-exposed HK-2 cells. In conclusion, DHA exerts protective effects on renal tubulointerstitial fibrosis in DN.

Early identification of kidney recovery in critically ill children and young adults undergoing continuous kidney support therapy (CKST) is essential to optimize care and minimize complications. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker of acute kidney injury, but its utility in predicting CKST duration and guiding timely liberation remains unclear. We retrospectively analyzed urinary uNGAL levels in pediatric intensive care unit (PICU) patients (aged 2 months to 25 years) who received CKST between July 2018 and April 2024. We evaluated two outcomes: (1) the ability of peak uNGAL levels during the first four days of CKST to predict prolonged therapy (>7 days), and (2) the performance of uNGAL measured during KST liberation attempts in predicting successful liberation. Among 57 patients, early peak uNGAL predicted CKST duration >7 days with good accuracy (AUC-ROC 0.85 [95% CI, 0.73-0.97], optimal cutoff 2600 ng/mL). uNGAL also showed excellent performance in predicting successful KST liberation (AUC-ROC 0.95 [95% CI, 0.89-1.00], optimal cutoff 900 ng/mL). uNGAL may be useful for predicting prolonged CKST duration and guiding KST liberation in critically ill children. Larger prospective studies are needed to confirm its role in personalized CKST management. Peak uNGAL levels within the first four days of CKST are strongly associated with treatment duration >7 days, showing good predictive accuracy. uNGAL demonstrates excellent performance in identifying patients likely to achieve successful KST liberation. uNGAL measured during KST may support clinical decision-making by providing timing insights, potentially optimizing treatment duration in critically ill pediatric patients.

Introduction:Cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CABG) often causes kidney dysfunction and increases morbidity and mortality.Aims:To evaluate the effects of CPB on kidney structures of patients submitted to CABG using serum and urinary biomarkers.Methods:This prospective study included patients who underwent CABG over a 14-month period. Data related to clinical, surgical, and laboratory were collected. The glomerular filtration rate was estimated using the CKD-EPI equation. The urinary biomarkers trialed were nephrin, KIM-1, MCP-1, Syndecan-1, and NGAL.Results:Out of 30 patients enrolled, 22 were assessed. The mean age was 65 years and most were male. During CABG, the On-pump group had increased urinary nephrin (p = 0.007) and urinary (p = 0.036) and serum NGAL (p = 0.030) levels compared to the Off-pump group. Moreover, intraoperatively, in the On-Pump clusters, the urinary NGAL was correlated with the decrease of glomerular filtration rate in the first 48 hours after CABG (Rho = − 0.838, p = 0.009). There was no statistical difference in clinical and surgical aspects between groups according to use of CBP during CABG.Conclusion:CBP procedure used during CABG was associated with relevant effects on kidney structure, such as podocyte and tubular injury. Urinary NGAL was able to predict an impairment of glomerular filtration 48 hours after CABG.

Nephrotic syndrome is a common glomerular disorder. Treatment typically begins with corticosteroids, but patient response varies. Differentiating between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) early in the disease course is important, as SRNS is associated with a higher risk of poor long-term outcomes. Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker released in response to tubular injury, has emerged as a potential non-invasive marker for renal damage. We conducted a systematic review and meta-analysis of studies reporting NGAL levels in SSNS and SRNS, based on the PRISMA guidelines. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, ScienceDirect, and the WHO Virtual Health Library Regional. The statistical analysis was performed using a random-effects model to estimate the standardized mean difference (SMD) with a 95% confidence interval. A total of 16 studies were included. Meta-analyses revealed significantly higher urinary NGAL levels in both SSNS and SRNS patients compared to healthy controls. Urinary NGAL levels were significantly higher in SSNS and SRNS patients compared to healthy controls, with SMD = 0.78 (95% CI: 0.434-1.128, P < .001) and SMD = 2.56 (95% CI: 1.152-3.971, P < .001), respectively. Patients with SRNS had markedly higher urinary NGAL levels than those with SSNS (SMD = 1.889, 95% CI: 0.819-2.959, P < .001). ROC analyses across several studies demonstrated moderate to strong discriminative ability of urinary NGAL in distinguishing between SRNS and SSNS. Urinary NGAL demonstrated strong potential as a non-invasive biomarker for distinguishing between SRNS and SSNS, supporting its clinical utility in early diagnosis, risk stratification, and management.

Differentiating functional acute kidney injury (AKI) from structural/intrinsic AKI with tubular injury remains a clinical challenge. Urinary NGAL (uNGAL) has shown promise in distinguishing these conditions. This study evaluated the implementation of uNGAL in a heterogeneous medical cohort at an academic tertiary care center in Ireland over a three-year period. A retrospective audit was conducted from 2020-2023. Standard clinical data around the time of AKI and uNGAL request were recorded. Blinded case adjudication of the differential diagnosis of AKI cause using the standard clinical information (but not urine NGAL results) was performed by two expert Nephrologists. Analysis of uNGAL focused on the accuracy in differentiating adjudicated (Intra-renal) AKI from Non-intrinsic AKI (Pre-renal & Post-renal). A total of 323 uNGAL tests were performed, with 292 AKI cases adjudicated. Intrinsic AKI cases had significantly higher uNGAL and uNGAL/Cr levels than non-intrinsic cases (p < 0.001), including after excluding UTI cases. uNGAL (AUC 0.71; 95% CI: 0.65-0.77) and uNGAL/Cr (AUC 0.73; 95% CI: 0.67-0.79) showed moderate discriminative performance. uNGAL (threshold 150 ng/ml) had high sensitivity (0.87) and negative predictive value (0.82). uNGAL/Cr was similar at the 288 ng/mg threshold. Discriminative performance improved for uNGAL and uNGAL/Cr, but not for serum creatinine, fractional excretion of sodium (FENa), or serum urea, after excluding UTI cases. Both uNGAL (aOR 2.05; 95% CI: 1.59-2.71) and uNGAL/Cr (aOR 2.07; 95% CI: 1.64-2.68) were independently associated with intrinsic AKI. Adding these biomarkers to a logistic regression model significantly improved discrimination performance (AUC 0.79; 95% CI: 0.76-0.84; p = 0.0116). The use of uNGAL improved the discriminative accuracy of differential diagnosis of AKI in clinical practice by differentiating intrinsic AKI from non-intrinsic. Specificity was low at the manufacturer's recommended threshold (150ng/ml), but the sensitivity and NPV were high in all analyses. These findings support the clinical utility of uNGAL at the 150ng/ml threshold as a "rule-out" test for intrinsic AKI, thereby helping to direct management toward functional (pre-renal) or obstructive (post-renal) causes when uNGAL is negative.

Occupational heat stress among wildland firefighters (WFFs) performing arduous work or working in hot work environments may cause kidney dysfunction and injury. Kidney function and injury biomarkers (serum and urine) were measured among 39 WFFs pre- and post-fire season in 2018-2019. The same biomarkers were measured in 19 of these 39 WFFs over 3 days during a 2019 mid-season fire incident. Median differences in biomarker concentrations across the fire season and across the mid-season incident were evaluated using the Sign test. The primary outcome of interest was the cystatin C-based estimated glomerular filtration rate (eGFRcys). The eGFRcys decreased (median difference = -5 mL/min/1.73 m2; interquartile range [IQR] = -8, -2 mL/min/1.73 m2; p = 0.008), and 53% of participants lost ≥ 2% of their body weight across the first day of the mid-season fire incident. Median eGFRcys did not decrease across the fire season (median difference = 0 mL/min/1.73 m2; IQR = -5, 5 mL/min/1.73 m2; p = 0.52). The albumin-creatinine ratio and the ratios of urine kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin concentrations to urine osmolality increased across ≥ 1 day during the mid-season incident. A temporary decrease in kidney function and changes in biomarkers of kidney injury were observed during a wildland fire incident. Additional research is warranted to confirm these findings, assess associations with occupational heat stress, and determine whether persistent, clinically relevant kidney injury and dysfunction occur among WFFs over time. The findings also support the need for continued efforts to promote optimal hydration of WFFs.

Role of Urinary Biomarkers in the Postoperative Follow-Up of Ureteropelvic Junction Obstruction: A Preliminary Report.

Children with febrile urinary tract infections (fUTI), especially those with acute pyelonephritis (APN) and vesicoureteral reflux (VUR), may face several complications, especially kidney scarring. Different biomarkers, such as urinary neutrophil gelatinase-associated lipocalin (uNGAL) and procalcitonin (PCT), have been studied for predicting kidney scarring without the need for a DMSA scan. This systematic review and meta-analysis examines the role of biomarkers in pediatric patients with a history of fUTI and their prognostic value in the diagnosis of APN and prediction of kidney scarring. A search through major databases (MEDLINE/PubMed and Scopus) was conducted from inception until January 2, 2025. The mean difference (95% CI) was applied. A p < 0.05 was considered statistically significant. The systematic review included 2300 participants from 28 studies. Procalcitonin and uNGAL were higher in individuals with scarring after a fUTI episode compared to those without scarring (p = 0.035 and p < 0.0001, respectively). In addition, PCT was higher in patients with APN compared to those with lower UTI (p < 0.0001). Finally, the good and moderate overall diagnostic accuracy (I2 = 29.8%) of PCT in predicting APN (AUC: 0.861) and uNGAL (I2 = 16.8%) in predicting kidney scarring after an episode of fUTI (AUC: 0.74), respectively, should be considered. This study showed that PCT and uNGAL can detect APN and kidney scarring after fUTI. More studies should be conducted exploring the role of other biomarkers in scarring after an episode of fUTI in pediatric patients with or without VUR.

Background: Acute Kidney Injury (AKI) is a common and serious complication following cardiac surgery, associated with adverse outcomes and increased healthcare costs. Early identification of AKI is critical for timely intervention and improved prognosis. However, serum creatinine—the traditional biomarker for renal function—lacks sensitivity in the early stages due to its delayed rise. Neutrophil Gelatinase-Associated Lipocalin (NGAL) has emerged as a promising early biomarker. Objective: This study aimed to compare the diagnostic performance of urinary NGAL versus serum creatinine for early prediction of AKI in post-cardiac surgery patients. Methodology: This descriptive cross-sectional study was conducted from May 2023 to June 2024 and included 123 patients aged 40–70 years undergoing elective cardiac surgery. Patients with pre-existing chronic kidney disease or recent urological procedures were excluded. Urinary NGAL levels were measured 2 hours postoperatively, while serum creatinine was assessed at 48 hours. Diagnostic performance was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy. Results: Urinary NGAL demonstrated superior diagnostic accuracy with a sensitivity of 92.0%, specificity of 81.25%, PPV of 88.46%, NPV of 86.67%, and overall accuracy of 87.80% in predicting AKI. In comparison, serum creatinine exhibited lower diagnostic metrics, reinforcing the early predictive value of NGAL. Conclusion: Urinary NGAL outperforms serum creatinine as an early biomarker for AKI following cardiac surgery. Incorporating urinary NGAL testing into routine postoperative care may enhance early detection and improve clinical outcomes. Further large-scale, multicenter studies are warranted to validate these findings across diverse populations. Keywords: Acute Kidney Injury, Biomarker, Cardiac Surgery, Neutrophil Gelatinase-Associated Lipocalin, Serum Creatinine.

Patients with diabetic ketoacidosis are at heightened risk of increased morbidity and death due to acute kidney injury (AKI). Early AKI detection is therefore essential. A new biomarker called urinary neutrophil gelatinase-associated lipocalin (NGAL) has been used to predict early AKI in several diseases. We aimed to determine the predictive role of urinary NGAL for AKI development in adults with diabetic ketoacidosis. The study included 56 patients with diabetic ketoacidosis classified into 2 groups based on urinary NGAL levels on admission to the intensive care unit (ICU). Group A had high urinary NGAL levels (≥197.5 nmol/L), and group B had urinary NGAL levels below 79.0ng/mL. The primary outcome was the development of AKI during the ICU stay. No statistically significant differences in serum creatinine, estimated glomerular filtration rate (eGFR), and serum urea nitrogen were observed between the 2 groups upon admission. On the seventh day of admission, eGFR and urine output were lower in group A than in group B. Within groups A and B, 71.1% and 38.9%, respectively, developed AKI. A urinary NGAL cutoff value above 583.75nmol/L predicted AKI. Urinary NGAL at a cutoff value above 583.75nmol/L on admission has a good predictive value for AKI in patients with diabetic ketoacidosis. Early detection of AKI could improve diabetic ketoacidosis outcomes and decrease the risk of chronic kidney disease in individuals with diabetes.