Serum Neutrophil Gelatinase-associated Lipocalin Levels Research Articles

Neutrophil gelatinase-associated lipocalin as a biomarker for detection of early renal impairment in Iraqi patients with multiple myeloma.

To evaluate the serum neutrophil gelatinase-associated lipocalin levels in multiple myeloma patients as an indicator of disease progression. The case-control study was conducted at the Clinical Biochemistry Department of the National Centre of Haematology, Mustansiriyah University, Baghdad, Iraq, from October 2020 to July 2021, amd comprised diagnosed multiple myeloma patients and healthy controls of either gender aged 40-60 years. Neutrophil gelatinaseassociated lipocalin and renal functions were measured for all patients in addition to obtaining a complete history and physical examination. Data was analysed using MedCalc. Of the 60 sujects, 30(50) were cases with mean age 64±2.1 years and 30(50%) were controls with mean age 60 ±3.2 years. There were 18(68%) males among the cases and 17(55%) among the controls. In the cases group, mean levels of creatinine, urea and neutrophil gelatinase-associated lipocalin were 1.62±0.85mg/dl, 55.56±28.05mg/dl and 389.39±116.12pg/mL, respectively. The corresponding values for the controls were 0.9518±0.1623mg/dl, 30.17±8.47mg/dl and 120.82±68'52pg/ml. The neutrophil gelatinase-associated lipocalin cutoff level >190pg/ml in multiple myeloma patients was strongly associated with renal impairment (p<0.001). Neutrophil gelatinase-associated lipocalin was found to be an accurate indicator of early kidney disease in patients with de novo multiple myeloma.

2,5-Dihydroxyacetophenone attenuates acute kidney injury induced by intra-abdominal infection in rats.

As one of the most serious complications of sepsis, acute kidney injury (AKI) is pathologically associated with excessive inflammation. 2,5-Dihydroxyacetophenone (DHAP) is isolated from Radix rehmanniae praeparataand exhibit potent anti-inflammatory property. This research aimed at determining the role of DHAP in sepsis-associated AKI (SA-AKI) and the underlying mechanism. Plasma creatinine (Cre), blood urea nitrogen (BUN), tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels of SA-AKI patients were detected to evaluate their clinical characteristics. SA-AKI rat models were established by using caecum ligation puncture (CLP) surgery. CLP-induced rats were administered via oral gavage with 20 or 40 mg DHAP after 2 h of CLP surgery. Subsequently, survival rates, serum indexes, histopathological changes, inflammatory factors, renal function indexes and extracellular regulated protein kinases (ERK) and nuclear factor-κB (NF-κB) signalling pathways were detected. SA-AKI patients exhibited markedly higher levels of plasma Cre, BUN, TNF-α and IL-1β than healthy people. Compared with sham rats, CLP-induced septic rats showed significantly decreased survival rate, increased serum lactate dehydrogenase activity and serum lactate level, obvious renal histopathological injury, upregulated TNF-α, IL-1β and TGF-β1 levels, elevated serum creatinine, BUN and serum cystatin C concentrations, serum neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels and reduced renal artery blood flow. All the above CLP-induced changes in septic rats were mitigated after DHAP administration. Additionally, CLP-induced elevation in phosphorylated-ERK1/2 and nuclear NF-κB p65 protein levels was inhibited by DHAP treatment. DHAP hinders SA-AKI progression in rat models by inhibiting ERK and NF-κB signalling pathways.

The power of trans-sodium crocetinate: exploring its renoprotective effects in a rat model of colistin-induced nephrotoxicity.

Colistin, a multidrug-resistant gram-negative bacterial infection medication, has been associated with renal impairment and failure. Trans-sodium crocetinate (TSC), a saffron-derived chemical recognized for its antioxidant and nephroprotective properties, was studied in this study to determine its potential to alleviate the nephrotoxic effects of colistin. Forty-two male Wistar rats were randomly classified into seven groups (n = 6): (1) control (normal saline, 12 days, i.p.), (2) colistin (22 mg/kg, 7 days, i.p.), (3-5) colistin + TSC (25, 50, and 100 mg/kg, 12 days, i.p., starting from 5 days before colistin), (6) TSC (100 mg/kg, 12 days, i.p.), (7) colistin + vitamin E (100 IU/kg, 12 days, i.p). On day 13, the rats were euthanized and the serum content of creatinine, BUN, Na+, and K+, as well as oxidative stress (GSH, MDA, SOD, CAT), inflammatory (IL-1β), apoptotic (Bax, Bcl-2, caspase-3, 8, 9), and autophagy (Beclin-1, LC3) markers, NGAL, and histopathological changes in the kidney were measured. Colistin significantly increased serum creatinine, BUN, MDA, IL-1β, caspase-3,8,9, Bax, Beclin-1, LC3, and NGAL levels in kidney tissue. It also caused inflammation, focal necrosis of tubular epithelial cells, protein cast, and acute tubular necrosis. Furthermore, colistin decreased SOD, CAT, GSH, and Bcl-2 levels. TSC and vitamin E administration along with colistin restored most of the alterations induced by colistin. Overall, it could be concluded that colistin induces oxidative stress, inflammation, autophagy, and apoptosis, which can cause kidney injury. However, TSC can also be used as a therapeutic agent to reduce injuries caused by colistin.

Cerebrospinal Fluid Neutrophil Gelatinase-Associated Lipocalin as a Novel Biomarker for Postneurosurgical Bacterial Meningitis: A Prospective Observational Cohort Study

BACKGROUND AND OBJECTIVES: Postneurosurgical bacterial meningitis (PNBM) was a significant clinical challenge, as early identification remains difficult. This study aimed to explore the potential of neutrophil gelatinase-associated lipocalin (NGAL) as a novel biomarker for the early diagnosis of PNBM in patients who have undergone neurosurgery. METHODS: A total of 436 postneurosurgical adult patients were enrolled in this study. Clinical information, cerebrospinal fluid (CSF), and blood samples were collected. After the screening, the remaining 267 patients were divided into the PNBM and non-PNBM groups, and measured CSF and serum NGAL levels to determine the diagnostic utility of PNBM. Subsequently, patients with PNBM were categorized into gram-positive and gram-negative bacterial infection groups to assess the effectiveness of CSF NGAL in differentiating between these types of infections. We analyzed the changes in CSF NGAL expression before and after anti-infection treatment in PNBM. Finally, an additional 60 patients were included as an independent validation cohort to further validate the diagnostic performance of CSF NGAL. RESULTS: Compared with the non-PNBM group, CSF NGAL was significantly higher in the PNBM group (305.1 [151.6-596.5] vs 58.5 [30.7-105.8] ng/mL; P &lt; .0001). The area under the curve of CSF NGAL for diagnosing PNBM was 0.928 (95% CI: 0.897-0.960), at a threshold of 119.7 ng/mL. However, there was no significant difference in serum NGAL between the 2 groups (142.5 [105.0-248.6] vs 161.9 [126.6-246.6] ng/mL, P = .201). Furthermore, CSF NGAL levels were significantly higher in patients with gram-negative bacterial infections than those with gram-positive bacteria (P = .023). In addition, CSF NGAL levels decrease after treatment compared with the initial stage of infection (P &lt; .0001). Finally, in this validation cohort, the threshold of 119.7 ng/mL CSF NGAL shows good diagnostic performance with a sensitivity and specificity of 90% and 80%, respectively. CONCLUSION: CSF NGAL holds promise as a potential biomarker for the diagnosis, early drug selection, and efficacy monitoring of PNBM.

Role of Serum and Urine Neutrophil Gelatinase-associated Lipocalin as Biomarkers for Assessing Graft Function in Kidney Transplant Recipients.

The existing biomarkers used to promptly identify graft dysfunction after kidney transplantation lack consistency. Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker but its levels measured from serum and urine have demonstrated varying predictive values. Our study aimed to explore the potential of NGAL as a biomarker in predicting graft dysfunction in kidney transplant patients, including live and deceased donor recipients. A single-centered observational cohort study with live and deceased kidney recipients as participants was conducted between 2018 and 2022 at a tertiary care hospital in Southern India. Serum creatinine levels were monitored daily; creatinine reduction on day two and day seven were calculated. The recipients were categorized based on graft recovery into three groups: delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Analysis of serum and urine NGAL was conducted two hours after the transplant and their predictive values were evaluated by the area under the curves (AUC) method. Of the 40 participants, 34 (85.0%) received their transplant from live-related donors, while six (15.0%) received kidneys from deceased donors. DGF occurred in four (10.0%) patients, SGF in 12 (30.0%), and 24 (60.0%) patients achieved IGF. Serum NGAL demonstrated higher sensitivity compared to urine NGAL. At a cut-off value of 678 ng/mL (AUC = 0.77), serum NGAL showed 90.0% sensitivity and 53.0% specificity. Urine NGAL had 70.0% sensitivity and 74.0% specificity at a cut-off value of 489 ng/mL (AUC = 0.72). Kidney recipients in SGF and DGF categories had elevated levels of serum and urine NGAL compared to those without IGF. Although serum NGAL showed higher sensitivity than urine NGAL in predicting graft dysfunction, both markers lacked the specificity needed for accurate predictions.

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients

IntroductionSystemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost.MethodsTwenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2).ResultsSSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC.Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2.ConclusionsSSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.

Plasma proenkephalin andneutrophil gelatinase-associated lipocalin predict mortality in ICU patients with acute kidney injury.

Acute kidney injury (AKI) is a common complication in patients admitted to intensive care unit (ICU) and mortality rates for this condition are high. To reduce the high incidence of short-term mortality, reliable prognostic indicators are required to facilitate early diagnosis and treatment of AKI. We assessed the ability of plasma proenkephalin (p‑PENK) and plasma neutrophil gelatinase-associated lipocalin (p‑NGAL) to predict 28-day mortality in AKI patients in intensive care. This prospective study, carried out between January 2019 and December 2019, comprised 150 patients (100 male) diagnosed with AKI after excluding 20 patients discharged within 24 h and those with missing hospitalization data. Blood samples were collected to determine admission p-PENK and p-NGAL levels. The study outcome was 28‑day mortality. The mean patient age was 68 years (female, 33%). The average P‑PENK and p‑NGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. P‑PENK levels >0.36 ng/µL and p‑NGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28‑day mortality for patients with AKI (adjusted hazard ratios 0.785 [95% confidence interval 0.706-0.865, P<0.001] and 0.700 [95% confidence interval 0.611-0.789, P<0.001], respectively). This association was significant for mortality in patients in intensive care with AKI. Baseline p-PENK (0.36 ng/µL) and p-NGAL (230.30 ng/mL) levels and their respective cut-off values showed clinical value in predicting 28-day mortality. Serum PENK and NGAL levels, when used in conjunction, improved the accuracy of predicting 28-day mortality in patients with AKI while retaining sensitivity and specificity.

The utility of serum neutrophil gelatinase-associated lipocalin level on predicting autosomal dominant polycystic kidney disease progression.

We focused on neutrophil gelatinase-associated lipocalin (NGAL) and autosomal dominant polycystic kidney disease (ADPKD) progression. ADPKD patients with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 were included. Serum NGAL level and NGAL to eGFR ratio (NGR), height-adjusted total kidney volume (hTKV) were assessed initially. Patients were followed-up for 5 years. Sixty one patients were enrolled and initial eGFR was 73.6 (48.9-101.5) ml/min/1.73m2. EGFR declined by 3.7 mL/min/1.73m2 per year. Thirty four patients (55.7%) exhibited rapid progression. Rapid progression group had lower serum NGAL levels (p < 0.001) and higher hTKV (p < 0.001). Lower serum NGAL level was a risk factor for rapid progression (p < 0.001). NGR was not associated with rapid progression. Serum NGAL level was predictive in for rapid progression ROC analysis (cut-off <10.62 ng/mL). Relatively lower serum NGAL levels can predict worse outcomes in ADPKD and can provide risk stratification in patients with ADPKD.

Role of Osteopontin and NGAL in Differential Diagnosis of Acute Exacerbations of COPD and Pneumonia

Objective: Chronic Obstructive Pulmonary Diesase (COPD) is an inflammatory lung disease that progresses with attacks. Pneumonia is an infectious lung disease that progresses with lung infiltrations. Osteopontin (OP) is a cytokine which participates in inflammation. Neutrophil Gelatinase Associated Lipocalin (NGAL) is an antimicrobial peptide with neutrophil activation and antibacterial properties. In this study, serum OP and NGAL levels were assayed in COPD exacerbation, stabile COPD and pneumonia. The aim of our study is to assess the importance of NGAL and OP levels as biomarkers in the differential diagnosis of COPD and pneumonia. Material and Methods: One hundred twenty consecutive patients who were admitted to our department between May 2011 and August 2013 were included in the study. Serum OP and NGAL levels were measured with ELISA method within 24 hours following the determination of diagnosis. COPD acute exacerbation (AE-COPD) group was comprised of 95 patients (87 male and mean age 69.0±10.6), and the pneumonia group was comprised of 25 patients (16 male and mean age 57.5±22.9). Serum OP and NGAL levels of the patients in the AE-COPD group were re-measured within 30-45 days following acute exacerbation in stabile period. Results: Serum OP levels were higher in the pneumonia group compared to the AE-COPD group (93.47 ng/ml vs 53.10 ng/ml; p&lt;0.001). Multivariate regression analyses indicated that OP levels to be &gt;84 ng/ml is an independent predictor that increases risk for pneumonia more than 8-fold (95% CI, 2.43-26.59). Sensitivity and specificity of OP in the differentiation of pneumonias from AE-COPD were determined to 80% and 92%, respectively. Serum NGAL levels also increased as COPD severity increased and was found to be statistically significant (p: 0.032). Conclusion: It has been indicated that serum osteopontin level can be an independent predictor in differentiating COPD exacerbation from pneumonia. Additionally, as COPD severity (stage) increases, serum NGAL levels also increase, which may be helpful in assessing the severity of COPD.

The impact of renal tubulointerstitial dysfunction on the early and long-term prognosis in chronic heart failure patients with preserved left ventricular ejection fraction

Aim. To study the dependence of the early-term (1 year) and long-term (5 years) prognosis in patients with chronic heart failure (CHF) of ischemic origin with preserved left ventricular ejection fraction (LVEF) depending on renal tubulointerstitial functional disorders. Materials and methods. The study involved 88 patients (men – 46.6 % (n = 41); women – 53.4 % (n = 47)) with CHF of ischemic origin, stage II A–B, stage II–IV according to NYHA, 67 % (n = 59) with sinus rhythm, and 33 % (n = 29) with atrial fibrillation. Patients with sinus rhythm and atrial fibrillation were matched in age (p = 0.483), height (p = 0.345), weight (p = 0.317), body surface area (p = 0.153). NGAL levels were analyzed using an ELISA kit (E-EL-H0096, Elabscience, USA). NAG levels were analyzed using an ELISA kit (SEA 069 Hu, Cloud-Clone Corp., USA). KIM-1 levels were analyzed using an ELISA kit (SEA 785 Hu, Cloud-Clone Corp., USA). Kaplan–Meier curves and Cox proportional hazards regression analysis were performed. Results. No significant difference was found in the frequency of the cumulative endpoint during the first-year follow-up from the initial level of two markers of tubulointerstitial injury – KIM-1 (Log-Rank Test: p = 0.57529) and NAG (Log-Rank Test: p = 0.86001). According to the results of analysis of the Cox proportional hazards, only a tendency to increase in the risk factors of adverse events were observed in case of elevated KIM-1 (HR = 1.66; p = 0.5795) and NAG levels (HR = 1.1712; p = 0.8626) in this CHF patients’ cohort. Kaplan–Meier analysis revealed a probable (Log-Rank Test; p = 0.00141) increase in the frequency of the cumulative endpoint during the first year of follow-up in CHF patients with preserved LVEF due to increased serum NGAL level more than 168 ng/ml. According to the univariate model, an elevated serum NGAL level is associated with an increase in the relative risk by 4.2 times (95 % CI 1.78–16.89; p = 0.014). A reduced sodium level less than 142.5 mmol/l was associated with an increase in number of adverse cardiovascular events during the first-year follow- ups by 22 % (HR = 1.22, p = 0.029). After 5 years of follow-up, a decrease in sodium level less than 142.3 mmol/l is also characterized by a probable difference of the cumulative Kaplan–Meier’s curves (Cox–Mantel F-Test, p = 0.00287). According to the univariate model of Cox proportional hazards, the relative risk of adverse cardiovascular events in patients with CHF during the 5-year follow-up has a tendency to increase by 1.04 times (95 % CI 0.85–1.27; p = 0.72). Serum NGAL, a marker of renal tubulo-interstitial injury, doesn’t lose its properties as a powerful marker of an unfavorable long-term prognosis in patients with CHF with preserved LVEF (HR = 5.96; 95 % CI 1.17–30.50; p = 0.032). Conclusions. The most powerful factors of the early (1-year) prognosis of adverse cardiovascular events in CHF patients with preserved left ventricular ejection fraction are the marker of tubulointerstitial injury, serum NGAL over 168 ng/ml, as well as the marker of tubulointerstitial dysfunction – the serum sodium level less than 142.5 mmol/l. The electrolyte imbalance, decreased sodium level less than 142.3 mmol/l, remains a powerful marker of an unfavorable long-term 5-year prognosis in CHF patients with preserved left ventricular ejection fraction, meanwhile serum NGAL, a marker of renal tubulointerstitial injury, besides doesn’t lose its prognostic value (HR = 5.96; 95 % CI 1.17–30.50; p = 0.032), but also is independent from the parameters of the age (p = 0.409) and gender (p = 0.397) in such patients.

Assessment of Urinary and Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels as Novel Predictors for Vesicoureteral Reflux Diagnosis in Children with Febrile Urinary Tract Infection.

The invasive, expensive, and time-consuming nature of radiological examinations for vesicoureteral reflux (VUR) has compelled researchers to search for new markers to predict VUR. This study was designed to evaluate the usefulness of serum and urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in predicting the existence of VUR. This cross-sectional study involved all patients with a first febrile urinary tract infection (UTI) referred to Ali Asghar Children's Hospital. Each patient included in the study had clinical symptoms of pyelonephritis and a positive urine culture. The patients were divided into 2 groups: VUR and non-VUR. The serum and urinary NGAL levels were calculated in both groups. The receiver operating characteristic (ROC) curve was used to look for serum and urinary NGAL cut-points that differentiated the VUR group from the non-VUR group. Among the 40 children in the study, 23 belonged to the VUR group. The median age was 2.5 years (range, 0.3-8 years), and 35 patients were girls. ROC curve analysis showed that only the urinary NGAL level was significantly related to VUR. There was no association between serum NGAL levels and VUR. According to the ROC curve, a urinary NGAL level cut-off value of 15 ng/mL was likely to be diagnostic of VUR with 82.6% sensitivity and 58.8% specificity. The urinary NGAL level, specifically with a cut-off value of 15 ng/mL, can indicate the existence of VUR in patients with UTI with near-acceptable levels of sensitivity and specificity.

Renoprotective effect of diacetylrhein on diclofenac-induced acute kidney injury in rats via modulating Nrf2/NF-κB/NLRP3/GSDMD signaling pathways

Diclofenac (DF)-induced acute kidney injury (AKI) is characterized by glomerular dysfunction and acute tubular necrosis. Due to limited treatment approaches, effective and safe drug therapy to protect against such AKI is still needed. Diacetylrhein (DAR), an anthraquinone derivative, has different antioxidant and anti-inflammatory properties. Therefore, the aim of the current study was to investigate the renoprotective effect of DAR on DF-induced AKI while elucidating the potential underlying mechanism. Our results showed that DAR (50 and 100 mg/kg) markedly abrogated DF-induced kidney dysfunction decreasing SCr, BUN, serum NGAL, and serum KIM1 levels. Moreover, DAR treatment remarkably maintained renal redox balance and reduced the levels of pro-inflammatory biomarkers in the kidney. Mechanistically, DAR boosted Nrf2/HO-1 antioxidant and anti-inflammatory response in the kidney while suppressing renal TLR4/NF-κB and NLRP3/caspase-1 inflammatory signaling pathways. In addition, DAR markedly inhibited renal pyroptosis via targeting of GSDMD activation. Collectively, this study confirmed that the interplay between Nrf2/HO-1 and TLR4/NF-κB/NLRP3/Caspase-1 signaling pathways and pyroptotic cell death mediates DF-induced AKI and reported that DAR has a dose-dependent renoprotective effect on DF-induced AKI in rats. This effect is due to powerful antioxidant, anti-inflammatory, and anti-pyroptotic activities that could provide a promising treatment approach to protect against DF-induced AKI.

Deceased Kidney Donor Biomarkers: Relationship between Delayed Kidney Function and Graft Function Three Years after Transplantation.

With an increasing number of marginal donors, additional methods for the evaluation of cadaveric kidney quality are required. This study aimed to evaluate pretransplant deceased donor serum (s) and urine (u) biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18, and C-X-C motif chemokine 10 (CXCL10) for predicting early and late graft function. In total, 43 deceased kidney donors and 76 corresponding recipients were enrolled. Delayed graft function (DGF) occurred in 27.6% of cases. sIL-18, sKIM-1, uNGAL, and uKIM-1 were predictors of DGF. A model incorporating sIL-18, uKIM-1, and clinical factors was developed to predict DGF (AUROC 0.863). Univariate analysis showed a negative association between uKIM and graft eGFR at 6, 12, 24, and 36 months, but this was not confirmed in the multivariate analysis. In conclusion, we report a superior performance of donor biomarkers for predicting DGF and later graft function over serum creatinine. Higher levels of donor sIL-18 and uKIM in conjunction with expanded-criteria donors and longer cold ischemia times predicted DGF. With no renal tubular damage in zero-time donor biopsies, higher pretransplant urine and serum NGAL levels were associated with better allograft function one year after transplantation, and sNGAL with graft function three years after transplantation.

Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Post-Acute COVID-19 Syndrome.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is part of the innate immune system and acute-phase protein. Current data state that acute COVID-19 patients have higher levels of serum NGAL (sNGAL), but it is not known if higher protein levels are maintained in the convalescents. As post-COVID complications are currently the most important aspect of the disease, further research into metabolic and immunological consequences of the disease is needed. Methods: We aimed to determine the levels of sNGAL in a patient population 3 months after the acute phase of the disease and to identify the factors that may be related to the elevation of sNGAL levels in the mentioned cohort. The study included 146 patients diagnosed with COVID-19 in different stages of the disease. Three months after COVID-19 diagnosis, patients' sera were sampled and tested. Results: We demonstrate an association between the severity of the disease in the acute phase and elevated sNGAL levels three months after recovery, with the exception of the most severe hospitalized patients, who received early treatment. Moreover, we establish that sNGAL levels could be associated with prolonged dyspnea and the regulation of hunger and satiety in COVID-19 convalescents. Conclusions: These observations support the view that the introduction of antiviral treatment, steroids, and intense oxygen therapy reduces post-COVID immune-associated complications.

Kidney protective effect of sitagliptin in 5-fluorouracil-challenged rats

The possible protective effect of sitagliptin (SIT) against nephrotoxicity induced by a single dose 5-fluorouracil (5-FU) (150 mg/kg, i.p.) was investigated in rats. SIT treatment (5 and 10 mg/kg/day, p.o.) was given for 7 days, starting 5 days before 5-FU administration. Both SIT doses caused significant reductions of serum creatinine and neutrophil gelatinase-associated lipocalin levels in rats received 5-FU. Both doses of SIT also significantly decreased malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65 (NF-κB p65), Bax/Bcl-2 ratio, and cleaved caspase-3 in kidneys of 5-FU-challenged rats. Additionally, SIT, at both doses, significantly increased renal total antioxidant capacity and nuclear factor erythroid 2related factor 2 (Nrf2) in rats received 5-FU. Besides, SIT markedly attenuated the 5-FU-induced histopathological kidney tissue injury in rats. It was concluded that SIT, at both doses, provided a significant nephroprotective effect in 5-FU-challenged rats, through its antioxidant, antiinflammatory, and antiapoptotic activities, and by modulating Nrf2 and NF-κB pathways.

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study

BackgroundRhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group.ResultsBlood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment.ConclusionsTreatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Can neutrophil gelatinase-associated lipocalin be a novel and efficient marker to predict the clinical course of acute pancreatitis?

This study aimed to determine the value of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels to predict the severity of the disease and to identify its correlation with White Blood Cell (WBC), C-reactive protein (CRP), and high-sensitivity C-reactive protein (hs-CRP) levels in acute pancreatitis (AP). The study sample included 86 AP-diagnosed patients in the study group and 77 age- and gender-matched healthy volunteers with no comorbidity in the control group. The WBC, CRP, hs-CRP, and NGAL levels were examined at the time and 24 hours after diagnosis. Between the control group and the study group, a significant difference with and without necrosis in terms of NGAL averages (p=0.003) at the time of admission was observed. The mean level of the 24th-hour NGAL in the study group with necrosis (132.7±11.7 ng/ml) was found to be higher than the mean of the 24th-hour NGAL (117.5±22.6 ng/ml) in the study group without necrosis (p=0.032). Additionally, a significant difference was observed between the control group and the study group with and without necrosis in terms of CRP averages evaluated at admission. When the correlation of NGAL levels with WBC, CRP, and hs-CRP levels at the admission (r=0.224, p=0.038) and at the 24th h (r=0.389, p<0.001) are evaluated, weak correlations between NGAL and WBC levels were identified, but no correlation between NGAL and CRP and hs-CRP levels were observed. The usability of serum NGAL levels to predict the development of necrotizing pancreatitis in the early period was evaluated. Serum NGAL levels were found to be higher in the study group than in the control group, but there was no statistically significant difference between the mean values of 0th and 24th h NGAL values in any of the groups with/without pancreatic necrosis and the total study group was observed. More research is needed on the subject, with larger sampling sizes.

Correlation of Serum Neutrophil Gelatinaseassociated Lipocalin with Clinical Severity Score in Patients with Acute Coronary Syndrome: A Cross-sectional Study

Introduction: Acute Coronary Syndrome (ACS) is a term that encompasses various clinical presentations such as ST-Segment Elevation Myocardial Infarction (STEMI), Non STEMI (NSTEMI), or unstable angina. Neutrophil Gelatinase-associated Lipocalin (NGAL), also known as lipocalin-2, belongs to the lipocalin category of extracellular proteins. Recent research indicates that NGAL levels are increased in different cardiac situations, regardless of the presence of acute renal injury. Aim: To compare the levels of serum NGAL and Global Registry of Acute Coronary Events (GRACE) scores between cases with ACS and Angio-negative cases, and to study the correlation of serum NGAL with the GRACE score (clinical severity score) in ACS patients. Materials and Methods: A cross-sectional study was conducted with 128 patients at the Department of Biochemistry, MKCG Medical College and Hospital, Berhampur, Odisha, India, presenting to the Cardiac Emergency Department from November 2020 to August 2021. Coronary Angiograms (CAG) were done to confirm the presence of Coronary Artery Disease (CAD), and patients were grouped accordingly as Group-1 with ACS patients and Group-2 with angiogram-negative cases. Apart from the routine work-up, including serum urea and creatinine, serum electrolytes, fasting blood sugar, lipid profile, and management, all patients underwent determination of serum NGAL levels and GRACE score at admission. The data were analysis using student’s t-test and Pearson’s correlation test. Results: Among the 128 participants (64 cases in Group-1 and 64 cases in Group-2), Group-1 comprised 37 cases of STEMI, 26 cases of NSTEMI, and one case of unstable angina. Serum NGAL levels were significantly elevated in patients with CAGproven ACS (140.89±56.47 ng/mL) without any renal dysfunction, sepsis, or overt infection compared to patients without CAD on CAG (52.01±18.39 ng/mL) (p&lt;0.0001). The serum NGAL level exhibited a positive correlation of 0.359 (p=0.004) with the severity of ACS, as measured by the GRACE score. Conclusion: The present study suggests that serum NGAL in patients with ACS may serve as a potential novel biomarker for risk stratification and predicting the severity of the disease.

Protective role of alpha-lipoic acid against rhabdomyolysis-induced acute kidney injury in rats.

Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats. Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins. A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-α protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities. Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI.

Serum Neutrophil Gelatinase-associated Lipocalin: A Potential Marker of Impending Acute Kidney Injury in Sepsis

Abstract Introduction: Kidney injury is an inherent component of sepsis. Serum creatinine (S. Cr) as a marker of kidney injury has certain pitfalls and may not rise until significant kidney function has been lost. This study evaluated neutrophil gelatinase-associated lipocalin (NGAL) as a marker of impending acute kidney injury (AKI) in sepsis. Materials and Methods: A hospital-based cross-sectional, observational analytic study was conducted during one calendar year among patients admitted to medicine wards/intensive care units of a tertiary care hospital in Western India. A total of 80 study participants of age above 18 years fulfilling the criteria of sepsis were recruited in the study according to the Sepsis-3 criteria. Patients below 18 years of age, pregnant women, patients with known kidney diseases, malignancies, autoimmune diseases, and exposure to nephrotoxic agents (i.e. aminoglycoside, angiotensin-converting-enzyme inhibitors, and contrast agents) within the past 2 months, and patients who failed to give consent were excluded from the study. Clinical and biochemical data were collected till Day 7. Sequential organ failure assessment (SOFA) scores were calculated on Day 1 and Day 3. NGAL levels were measured on Day 3. Results: The mean age was 48 ± 19 years, with a male preponderance (63.8%). The mean of SOFA score on Day 1 and Day 3 was 9.84 ± 3.19 and 13.75 ± 3.14, respectively. The mean serum NGAL levels on Day 3 were 436.78 ± 242.23 ng/ml. The mean serum urea on Day 7 (86.99 ± 22.88 mg/dL) was significantly higher than on Day 3 (38.64 ± 9.49 mg/dL) (P = 0.004). Similarly, the mean S. Cr on Day 7 (2.97 ± 1.45 mg/dL) was significantly higher than on Day 3 (0.82 ± 0.23 mg/dL) (P = 0.033). The estimated glomerular filtration rate (eGFR) on Day 7 (35.42 ± 18.99 mL/min/1.73 m2) was also significantly lower in comparison to Day 3 (117.67 ± 56.10 mL/min/1.73 m2) (P &lt; 0.05). Serum NGAL showed a significant positive correlation with S. Cr on Day 3 (r = 0.3257, P = 0.003), Day 7 (r = 0.5944, P &lt; 0.00001), and mean change in S. Cr (r = 0.5562, P &lt; 0.00001). Serum NGAL showed a significant negative correlation with eGFR on Day 3 (r = −0.3061, P = 0.005), Day 7 (r = −0.4362, P = 0.00005), and mean change in eGFR (r = −0.1629, P &lt; 0.0001). Receiver-operating curve analysis showed 90.9% sensitivity and 98.3% specificity of NGAL (cutoff value 152 ng/ml) to predict impending AKI. Conclusion: Traditional marker of renal dysfunction (S. Cr, eGFR) had a significant correlation with NGAL. NGAL can predict impending AKI in sepsis patients earlier than S. Cr or eGFR.