RESUMO
Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.
Assuntos
Anorexia , Inibidor da Ligação a Diazepam , Animais , Inibidor da Ligação a Diazepam/metabolismo , Anorexia/tratamento farmacológico , Anorexia/metabolismo , Humanos , Camundongos Transgênicos , Camundongos , Anorexia Nervosa/metabolismo , Anorexia Nervosa/tratamento farmacológico , Lipocalina-2/metabolismo , Lipocalina-2/sangue , Hipotálamo/metabolismo , Masculino , Feminino , Camundongos Endogâmicos C57BL , Restrição Física , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacosRESUMO
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 (râ =â -0.634, Pâ <â .001) than that using SCr (ΔeGFRSCr; râ =â -0.437, Pâ =â .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass indexâ ≥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]) (Pâ =â .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.
Assuntos
Injúria Renal Aguda , Antibacterianos , Biomarcadores , Creatinina , Cistatina C , Receptor Celular 1 do Vírus da Hepatite A , Vancomicina , Humanos , Vancomicina/efeitos adversos , Vancomicina/farmacocinética , Vancomicina/administração & dosagem , Vancomicina/sangue , Biomarcadores/urina , Biomarcadores/sangue , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Injúria Renal Aguda/sangue , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Idoso , Receptor Celular 1 do Vírus da Hepatite A/análise , Cistatina C/sangue , Cistatina C/urina , Creatinina/sangue , Creatinina/urina , Taxa de Filtração Glomerular , Lipocalina-2/urina , Lipocalina-2/sangue , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina , Clusterina/urina , Clusterina/sangueRESUMO
INTRODUCTION: Acute kidney injury (AKI) defined by a substantial decrease in kidney function within hours to days and is often irreversible with higher risk to chronic kidney disease (CKD) transition. AREAS COVERED: The authors discuss the diagnostic and predictive utilities of serum and urinary biomarkers on AKI and on the risk of AKI-to-CKD progression. The authors focus on the relevant literature covering evidence of circulating and urinary biomarkers' capability to predict the transition of AKI to CKD. EXPERT OPINION: Based on the different modalities of serum and urinary biomarkers, multiple biomarker panel seems to be potentially useful to distinguish between various types of AKI, to detect the severity and the risk of AKI progression, to predict the clinical outcome and evaluate response to the therapy. Serum/urinary neutrophil gelatinase-associated lipocalin (NGAL), serum/urinary uromodulin, serum extracellular high mobility group box-1 (HMGB-1), serum cystatin C and urinary liver-type fatty acid-binding protein (L-FABP) were the most effective in the prediction of AKI-to-CKD transition regardless of etiology and the presence of critical state in patients. The current clinical evidence on the risk assessments of AKI progression is mainly based on the utility of combination of functional, injury and stress biomarkers, mainly NGAL, L-FABP, HMGB-1 and cystatin C.
Assuntos
Injúria Renal Aguda , Biomarcadores , Progressão da Doença , Insuficiência Renal Crônica , Humanos , Biomarcadores/urina , Biomarcadores/sangue , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Insuficiência Renal Crônica/urina , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Lipocalina-2/urina , Lipocalina-2/sangue , Prognóstico , Proteínas de Ligação a Ácido Graxo/urina , Proteínas de Ligação a Ácido Graxo/sangueRESUMO
OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) has been identified by the International Nephrology Association (INA) as a promising biomarker for the early evaluation of renal injury. This study aimed to develop and evaluate NGAL test strips as a rapid, simple, and economical method for the early diagnosis of acute kidney injury (AKI). METHODS: Recombinant prokaryotic expression vectors, purified NGAL protein, and anti-NGAL monoclonal antibodies were prepared. NGAL test strips were developed, and serum samples were collected from healthy individuals and patients with early-stage kidney injury at the Third Affiliated Hospital of Sun Yat-sen University between January 2023 and May 2024. Samples were tested using both the self-made strips and commercially available reagents. RESULTS: The NGAL test strip comprised a conjugate pad containing 0.2 µL of fluorescent microspheres conjugated with anti-NGAL monoclonal antibody (McAb7#), a test line containing 1 mg/mL of a different anti-NGAL monoclonal antibody (McAb3#), and a control line containing 0.5 mg/mL of goat anti-mouse IgG. The test utilized 60 µL of sample (30 µL serum diluted with 30 µL of sample diluent) and was completed within 15 min at 25 °C and 35 %-85 % relative humidity. The developed strip accurately detected NGAL, demonstrating good linearity within the range of 0-160 ng/mL (R2 = 0.9943). The sensitivity and specificity of the NGAL strip for AKI diagnosis were 86.1 % and 78.8 %, respectively, comparable to the performance of commercially available testing reagents. CONCLUSION: The developed test strip, utilizing anti-NGAL antibodies coupled with fluorescent microspheres, effectively detected trace amounts of NGAL protein in serum samples.
Assuntos
Injúria Renal Aguda , Lipocalina-2 , Microesferas , Humanos , Lipocalina-2/sangue , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Anticorpos Monoclonais/imunologia , Corantes Fluorescentes/química , Fitas ReagentesRESUMO
BACKGROUND: Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria. METHODS: A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment. RESULTS: Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group. CONCLUSION: Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.
Assuntos
Compostos Benzidrílicos , Biomarcadores , Diabetes Mellitus Tipo 2 , Glucosídeos , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Glicemia , Idoso , Lipocalina-2/sangue , Adulto , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/prevenção & controleRESUMO
Hemodialyzed patients have innate immunity activation and adaptive immunity senescence. Diabetes mellitus is a frequent cause for chronic kidney disease and systemic inflammation. We studied the immunological pattern (innate and acquired immunity) and the tissular regeneration capacity in two groups of hemodialyzed patients: one comprised of diabetics and the other of non-diabetics. For inflammation, the following serum markers were determined: interleukin 6 (IL-6), interleukin 1ß (IL-1ß), tumoral necrosis factor α (TNF-α), IL-6 soluble receptor (sIL-6R), NGAL (human neutrophil gelatinase-associated lipocalin), and interleukin 10 (IL-10). Serum tumoral necrosis factor ß (TNF-ß) was determined as a cellular immune response marker. Tissue regeneration capacity was studied using neurotrophin-3 (NT-3) and vascular endothelial growth factor ß (VEGF-ß) serum levels. The results showed important IL-6 and sIL-6R increases in both groups, especially in the diabetic patient group. IL-6 generates trans-signaling at the cellular level through sIL-6R, with proinflammatory and anti-regenerative effects, confirmed through a significant reduction in NT-3 and VEGF-ß. Our results suggest that the high serum level of IL-6 significantly influences IL-1ß, TNF-ß, NT-3, VEGF-ß, and IL-10 behavior. Our study is the first that we know of that investigates NT-3 in this patient category. Moreover, we investigated VEGF-ß and TNF-ß serum behavior, whereas most of the existing data cover only VEGF-α and TNF-α in hemodialyzed patients.
Assuntos
Interleucina-6 , Neurotrofina 3 , Diálise Renal , Humanos , Masculino , Interleucina-6/sangue , Feminino , Pessoa de Meia-Idade , Idoso , Fator de Necrose Tumoral alfa/sangue , Receptores de Interleucina-6 , Diabetes Mellitus , Lipocalina-2/sangue , Interleucina-1beta/sangue , Regeneração , Biomarcadores/sangue , Imunidade Inata , Inflamação , AdultoRESUMO
INTRODUCTION: Tachycardia caused by sympathetic overactivity impairs myocardial function and raises septic patients' mortality. This study examined whether tachycardia is associated with acute kidney injury (AKI) period-prevalence among critically ill patients with and without sepsis. METHODS: In 328 patients (119 sepsis and 209 non-sepsis) admitted to our intensive care unit (ICU), we assessed heart rate at ICU admission, plasma neutrophil gelatinase-associated lipocalin (NGAL) and N-terminal pro-B-type natriuretic peptide, and urinary L-type fatty acid-binding protein and N-acetyl-ß-
Assuntos
Injúria Renal Aguda , Estado Terminal , Sepse , Taquicardia , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/sangue , Sepse/complicações , Taquicardia/etiologia , Taquicardia/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Unidades de Terapia Intensiva , Lipocalina-2/sangue , Lipocalina-2/urina , Frequência Cardíaca , Proteínas de Fase Aguda/urina , Prevalência , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Acetilglucosaminidase/urinaRESUMO
OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.
Assuntos
Angiopoietina-2 , Biomarcadores , Proteína C-Reativa , Imunidade Inata , Insuficiência de Múltiplos Órgãos , Sepse , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Insuficiência de Múltiplos Órgãos/imunologia , Sepse/imunologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Angiopoietina-2/sangue , Idoso , Receptor Gatilho 1 Expresso em Células Mieloides , Componente Amiloide P Sérico/metabolismo , Pró-Calcitonina/sangue , Lipocalina-2/sangue , Interleucina-15/sangue , Fator de Necrose Tumoral alfa/sangue , AdultoRESUMO
BACKGROUND: Chronic liver disease is a common and important clinical problem.Hepatorenal syndrome (HRS) is a life threatening complication. Serum creatinine (Cr) remains the only conventional indicator of renal function. However, the interpretation of serum Cr level can be confounded by malnutrition and reduced muscle mass often observed in patients with severe liver disease. Here, we present a cross-sectional study to explore the sensitivity and specificity of other markers as urinary KIM-1 and NGAL for cases of HRS. METHODS: Cross-sectional study was conducted on 88 patients who were admitted to Alexandria main university hospital. Enrolled patients were divided in two groups; group 1: patients with advanced liver cirrhosis (child B and C) who have normal kidney functions while group 2: patients who developed HRS. Stata© version 14.2 software package was used for analysis. RESULTS: Group 1 included 18 males and 26 females compared to 25 males and 19 females in group 2 (p = 0.135). Only the urinary KIM-1 showed a statistically significant difference between both groups in the multivariate logistic regression analysis adjusted for gender, serum bilirubin, serum albumin, INR, serum K, AST and ALT levels. CONCLUSION: In conclusion, our study aligns with prior research, as seen in the consistent findings regarding Urinary NGAL elevation in cirrhotic patients with AKI. Urinary KIM-1, independent of Urinary NGAL, may have a role in precisely distinguishing between advanced liver cirrhosis and HRS and merits further exploration.
Assuntos
Biomarcadores , Receptor Celular 1 do Vírus da Hepatite A , Síndrome Hepatorrenal , Lipocalina-2 , Cirrose Hepática , Humanos , Masculino , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/urina , Estudos Transversais , Pessoa de Meia-Idade , Lipocalina-2/urina , Lipocalina-2/sangue , Biomarcadores/urina , Biomarcadores/sangue , Adulto , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/urina , Síndrome Hepatorrenal/diagnóstico , Modelos Logísticos , Idoso , Creatinina/sangue , Creatinina/urina , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: 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 (pPENK) and plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict 28-day mortality in AKI patients in intensive care. METHODS: 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 28day mortality. RESULTS: The mean patient age was 68 years (female, 33%). The average PPENK and pNGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. PPENK levels >0.36 ng/µL and pNGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28day 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. CONCLUSION: 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.
Assuntos
Injúria Renal Aguda , Biomarcadores , Encefalinas , Unidades de Terapia Intensiva , Lipocalina-2 , Humanos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/diagnóstico , Masculino , Feminino , Lipocalina-2/sangue , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Encefalinas/sangue , Biomarcadores/sangue , Precursores de Proteínas/sangue , Prognóstico , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Mortalidade HospitalarRESUMO
BACKGROUND: Lipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model. METHODS: We measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice. RESULTS: Serum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration. CONCLUSIONS: Our findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.
Assuntos
Biomarcadores , Fibrose Pulmonar Idiopática , Lipocalina-2 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Animais , Lipocalina-2/sangue , Lipocalina-2/metabolismo , Lipocalina-2/genética , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/genética , Masculino , Humanos , Feminino , Biomarcadores/sangue , Biomarcadores/metabolismo , Camundongos , Idoso , Pessoa de Meia-Idade , Prognóstico , Bleomicina/toxicidade , Progressão da Doença , Modelos Animais de DoençasRESUMO
BACKGROUND: Acute renal dysfunction and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is upregulated early (within 1 to 3 h) after murine renal injury and in pediatric acute renal dysfunction after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing acute renal dysfunction after cardiac surgery compared with patients without acute renal dysfunction. METHODS: After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. Acute renal dysfunction was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. RESULTS: Sixteen of 81 patients (20%) developed postoperative acute renal dysfunction, and the mean urinary NGAL concentrations in patients who developed acute renal dysfunction were significantly higher early after surgery (after 1 h, mean ± SD, 4,195 ± 6,520 vs. 1,068 ± 2,129 ng/ml; P < 0.01) compared with patients who did not develop acute renal dysfunction. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with acute renal dysfunction. In contrast, urinary NGAL in patients without acute renal dysfunction decreased rapidly after cardiac surgery. CONCLUSIONS: Patients developing postoperative acute renal dysfunction had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of acute renal dysfunction after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.
Assuntos
Injúria Renal Aguda , Proteínas de Fase Aguda , Biomarcadores , Procedimentos Cirúrgicos Cardíacos , Lipocalina-2 , Lipocalinas , Complicações Pós-Operatórias , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/urina , Feminino , Lipocalina-2/urina , Lipocalina-2/sangue , Masculino , Estudos Prospectivos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pessoa de Meia-Idade , Lipocalinas/urina , Idoso , Proteínas de Fase Aguda/urina , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Biomarcadores/urina , Biomarcadores/sangue , Proteínas Proto-Oncogênicas/urina , Proteínas Proto-Oncogênicas/sangue , AdultoRESUMO
INTRODUCTION: Systemic 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. METHODS: Twenty-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). RESULTS: SSc 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. CONCLUSIONS: SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.
Assuntos
Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Glucuronidase , Iloprosta , Proteínas Klotho , Lipocalina-2 , Escleroderma Sistêmico , Humanos , Iloprosta/administração & dosagem , Feminino , Pessoa de Meia-Idade , Masculino , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/sangue , Fatores de Crescimento de Fibroblastos/sangue , Lipocalina-2/sangue , Adulto , Glucuronidase/sangue , Citocinas/sangue , Idoso , Hipóxia/sangue , Infusões Intravenosas , Inflamação/sangue , Inflamação/tratamento farmacológicoRESUMO
Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury.
Assuntos
Injúria Renal Aguda , Precondicionamento Isquêmico , Lipocalina-2 , Fígado , Traumatismo por Reperfusão , Animais , Masculino , Camundongos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Biomarcadores , Modelos Animais de Doenças , Precondicionamento Isquêmico/métodos , Rim/metabolismo , Lipocalina-2/metabolismo , Lipocalina-2/sangue , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/metabolismoRESUMO
This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.
Assuntos
Lipocalina-2 , Esquizofrenia , Humanos , Masculino , Feminino , Lipocalina-2/sangue , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/fisiopatologia , Adulto , Caracteres Sexuais , Adulto Jovem , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Escalas de Graduação PsiquiátricaRESUMO
Acute kidney injury (AKI) is a critical complication of sepsis. There is a continuous need to identify and validate biomarkers for early detection. Serum and urinary biomarkers have been investigated, such as neutrophil gelatinase associated lipocalin (NGAL) and cystatin C (Cys C), but their reliability in the intensive care unit (ICU) remains unknown. Renal hemodynamics can be investigated by measuring the renal resistive index (RRI). This study aimed to compare the performance of RRI, serum NGAL (sNGAL), urinary NGAL (uNGAL), and serum Cys C levels as early predictors of the diagnosis and persistence of sepsis-associated AKI. A total of 166 adult patients with sepsis syndrome were enrolled immediately after ICU admission. Biomarkers were measured directly (T1) and on day 3 (T3). RRI was measured directly (T1) and 24 h later (T2). Patients were categorized (according to the occurrence and persistence of AKI within the first 7 days) into three groups: no AKI, transient AKI, and persistent AKI. The incidence rate of sepsis-associated AKI was 60.2%. Sixty-six patients were categorized as in the no AKI group, while another 61 were in transient AKI and only 39 were in persistent AKI. The RRI value (T1 ≥ 0.72) was the best tool for predicting AKI diagnosis (area under the receiver operating characteristic curve, AUROC = 0.905). Cys C (T1 ≥ 15.1 mg/l) was the best tool to predict the persistence of AKI (AUROC = 0.977). RRI (T1) was the best predictive tool for sepsis-associated AKI, while Cys C was the best predictor of its persistence and 28-day mortality.
Assuntos
Injúria Renal Aguda , Biomarcadores , Cistatina C , Lipocalina-2 , Sepse , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Biomarcadores/sangue , Biomarcadores/análise , Masculino , Feminino , Sepse/complicações , Sepse/fisiopatologia , Pessoa de Meia-Idade , Idoso , Cistatina C/sangue , Lipocalina-2/sangue , Lipocalina-2/urina , Lipocalina-2/análise , Valor Preditivo dos Testes , Artéria Renal/fisiopatologia , Artéria Renal/diagnóstico por imagem , Estudos Prospectivos , Unidades de Terapia Intensiva/estatística & dados numéricos , Unidades de Terapia Intensiva/organização & administração , Curva ROC , Diagnóstico PrecoceAssuntos
Injúria Renal Aguda , Biomarcadores , Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Humanos , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Lipocalina-2/sangueRESUMO
INTRODUCTION: Previous studies showed that the concentrations of selected chemokines are locally elevated in samples collected from the lumen of intracranial aneurysms (IA). Our objective was to determine whether the observed differences in analyte concentrations were influenced by the origin of the blood samples (i.e. cerebral versus peripheral), thus providing insight into the localised nature of these alterations and their significance in IA pathogenesis. MATERIAL AND METHODS: This prospective study included 24 patients with IA who underwent endovascular embolisation. Concentrations of selected analytes were analysed in blood samples from the IA lumen, feeding artery, and aorta. The analytes included MPO, Lipocalin-2/NGAL, sICAM-1, sVCAM-1, and serum amyloid A. RESULTS: Higher median plasma concentrations of MPO, lipocalin-2/NGAL, sVCAM-1, and SAA were found in samples obtained from the IA lumen and the feeding artery compared to the aorta. The concentration of sICAM-1 was significantly higher in the IA compared to the aorta, but did not differ between the proximal artery and the aorta. No significant differences in any analyte concentration were observed between the IA and the proximal artery. CONCLUSIONS: These findings suggest that the IA and the proximal vessel share similarities in the local immunological environment, which is different from that observed in the aorta. Further studies are needed to fully understand and elucidate these observations.