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Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.
[Box: see text].
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Biomarcadores , Cistatina C , Recien Nacido Prematuro , Tiempo de Internación , Lipocalina 2 , Sepsis , Humanos , Recién Nacido , Cistatina C/sangre , Cistatina C/orina , Lipocalina 2/orina , Lipocalina 2/sangre , Biomarcadores/orina , Biomarcadores/sangre , Sepsis/orina , Sepsis/diagnóstico , Sepsis/sangre , Masculino , Femenino , Recien Nacido Prematuro/orina , Proteínas de Fase Aguda/orina , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangreRESUMEN
Soluble biomarkers are paramount to personalized medicine. However, the in vivo turnover and biodistribution of soluble proteins is seldom characterized. The cleaved extracellular domain of the AXL receptor (sAXL) is a prognostic biomarker in several diseases and a predictive marker of AXL targeting agents. Plasma sAXL reflects a balance between production in tissues with lymphatic transport into the circulation and removal from blood by degradation or excretion. It is unclear how this transport cycle affects plasma sAXL levels that are the metric for biomarker development. Radiolabeled mouse sAxl was monitored after intravenous injection to measure degradation and urinary excretion of sAxl, and after intradermal injection to mimic tissue or tumor production. sAxl was rapidly taken-up and degraded by the liver and kidney cortex. Surprisingly, intact sAxl was detectable in urine, indicating passage through the glomerular filter and a unique sampling opportunity. The structure of sAxl showed an elongated, flexible molecule with a length of 18 nm and a thickness of only 3 nm, allowing passage through the glomerulus and excretion into the urine. Intradermally injected sAxl passed through local and distant lymph nodes, followed by uptake in liver and kidney cortex. Low levels of sAxl were seen in the plasma, consistent with an extended transit time from local tissue to circulation. The rapid plasma clearance of sAxl suggests that steady-state levels in blood will sensitively and dynamically reflect the rate of production of sAxl in the tissues but will be influenced by perturbations of liver and kidney function.
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Tirosina Quinasa del Receptor Axl , Biomarcadores , Proteínas Proto-Oncogénicas , Proteínas Tirosina Quinasas Receptoras , Animales , Proteínas Tirosina Quinasas Receptoras/metabolismo , Ratones , Distribución Tisular , Biomarcadores/orina , Biomarcadores/sangre , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangre , Hígado/metabolismo , Humanos , FemeninoRESUMEN
BACKGROUND AND AIMS: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase-associated lipocalin (u-NGAL), urinary beta-2-microglobulin (u-B2M), urinary osteopontin (u-OPN), urinary trefoil factor 3 (u-TFF3) and urinary Cystatin C (u-Cys). METHODS: This is a case-control study investigating the following urinary biomarkers of tubular damage: u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys, in patients with mild acute hyperbilirubinemia. Seventy-four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. RESULTS: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u-NGAL values (OR = 3.8, 95% CI 1.07-13.5, p = .03) and u-B2M (OR = 9.4, 95% CI 2.3-38.9, p = .0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. CONCLUSIONS: This study demonstrated increased urinary biomarkers of tubular damage (u-NGAL, u-B2M, u-OPN, u-TFF3, and u-Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology).
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Lesión Renal Aguda , Biomarcadores , Lipocalina 2 , Humanos , Biomarcadores/orina , Biomarcadores/sangre , Estudios de Casos y Controles , Masculino , Femenino , Persona de Mediana Edad , Lesión Renal Aguda/orina , Lesión Renal Aguda/etiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lipocalina 2/orina , Lipocalina 2/sangre , Anciano , Cistatina C/sangre , Cistatina C/orina , Hiperbilirrubinemia/complicaciones , Hiperbilirrubinemia/sangre , Hiperbilirrubinemia/orina , Microglobulina beta-2/orina , Microglobulina beta-2/sangre , Túbulos Renales/patología , Osteopontina/orina , Osteopontina/sangre , Lipocalinas/orina , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangre , Modelos Logísticos , Adulto , Proteínas de Fase Aguda/orina , Bilirrubina/sangre , Bilirrubina/orinaRESUMEN
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.
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Lesión Renal Aguda , Proteínas de Fase Aguda , Biomarcadores , Procedimientos Quirúrgicos Cardíacos , Lipocalina 2 , Lipocalinas , Complicaciones Posoperatorias , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/orina , Femenino , Lipocalina 2/orina , Lipocalina 2/sangre , Masculino , Estudios Prospectivos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Persona de Mediana Edad , Lipocalinas/orina , Anciano , Proteínas de Fase Aguda/orina , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Biomarcadores/orina , Biomarcadores/sangre , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangre , AdultoRESUMEN
Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35-2.3) versus 0.39 (0.15-0.71) P < 0.01) and U-NGAL (3164 pg/mL (100-147,555) versus 100 (100-14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.
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Lesión Renal Aguda , Dexmedetomidina , Enfermedades de los Perros , Endotoxemia , Animales , Perros , Lipocalina 2/orina , Creatinina/orina , Endotoxinas , Clusterina , Endotoxemia/veterinaria , Solución Salina , Lipocalinas/orina , Proteínas Proto-Oncogénicas/orina , Proteínas de Fase Aguda/metabolismo , Riñón/metabolismo , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/veterinaria , Biomarcadores , Enfermedades de los Perros/orinaRESUMEN
Cisplatin is a chemotherapeutic drug used to treat a great variety of solid tumors. Its dose is commonly limited by its nephrotoxicity, manifested as acute kidney injury (AKI). Erythropoietin (Epo) is a glycoprotein hormone that regulates the production of red blood cells. This study was performed to evaluate the presence of endogenous Epo in male Wistar rat urine and to analyse changes in urinary Epo levels in response to cisplatin- induced AKI. Dose-dependent studies and time-dependent experiments were performed to evaluate changes in urea nitrogen and creatinine in plasma as well as Epo, neutrophil gelatinase-associated lipocalin (NGAL), alkaline phosphatase (AP) activity, creatinine and total proteins in urine at 2 days post-dosing. Rats received 2, 5 or 10 mg/kg b.w., i.p. of cisplatin. At 5 mg/kg b.w., i.p. cisplatin, significant increases in urinary Epo were detected. Significant increases in urea nitrogen and creatinine in plasma, NGAL, AP, proteins, and Epo were observed in urine from rats that received 10 mg/kg b.w., i.p. of cisplatin. In the time-dependent experiments, rats were injected with a dose of 5 mg/kg b.w., i.p. of cisplatin, and sampling occurred 2, 4, and 14 days post-dosing. In these animals, there were significant increases in urea nitrogen and creatinine in plasma and total proteins, AP activity, Epo, and NGAL in urine on day 4. Urinary Epo was also detected on day 2. Taken together, these findings provide weight of evidence for urinary Epo as a promising early biomarker of cisplatin-induced AKI in male rats.
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Lesión Renal Aguda , Eritropoyetina , Masculino , Ratas , Animales , Lipocalina 2/efectos adversos , Cisplatino/toxicidad , Proteínas Proto-Oncogénicas/efectos adversos , Proteínas Proto-Oncogénicas/orina , Proteínas de Fase Aguda/orina , Creatinina , Lipocalinas/efectos adversos , Lipocalinas/orina , Ratas Wistar , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/orina , Eritropoyetina/efectos adversos , Biomarcadores/orina , UreaRESUMEN
BACKGROUND: Urinary NGAL (neutrophil gelatinase-associated lipocalin) levels have been shown to predict renal damage in various medical conditions. The present study was conducted to study the role of urinary NGAL levels in children with bladder exstrophy-epispadias complex post single-stage total reconstruction (SSTR) as markers of early renal function reduction. METHODS: Urine samples were collected from children with bladder exstrophy before SSTR (Group A, n = 11), 5 years post SSTR (Group B, n = 40) and controls (Group C, n = 41) and stored at - 20 °C. NGAL levels were estimated using double antibody sandwich ELISA. RESULTS: Mean NGAL levels in Groups A, B and C were 1.39, 34.24 and 2.58 ng/ml, respectively. Mean NGAL levels among Group B subjects with glomerular filtration rate (GFR) ≥ 80 ml/min/1.73 m2 body surface area (BSA) was 29.8 ng/ml, while it was 31.74 ng/ml in those with GFR < 80 ml/min. Urine samples were also evaluated 6 months post SSTR. Mean NGAL at 6 months was 6.76 ng/ml, while at 12 months it was 30.3 ng/ml, remaining > 30 ng/ml at 18 and 24 months. Dimercaptosuccinic acid (DMSA) scans did not show any scarring, and GFR on diethylenetriamine pentaacetate (DTPA) scans remained stable. CONCLUSIONS: Increasing levels of urinary NGAL following bladder-exstrophy and epispadias complex repair suggest that NGAL detects the earliest signs of renal damage even before any deterioration is observed in DMSA and/or DTPA-GFR scans. Further studies with an adequate sample size and periodic measurement of NGAL need to be performed before any definitive conclusion can be drawn.
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Extrofia de la Vejiga , Epispadias , Humanos , Niño , Lipocalina 2 , Extrofia de la Vejiga/cirugía , Proteínas Proto-Oncogénicas/orina , Lipocalinas/orina , Proteínas de Fase Aguda/orina , Biomarcadores/orina , Ácido PentéticoRESUMEN
Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in atherosclerotic plaques and implicated in the development of cardiovascular diseases. Peripheral arterial disease (PAD) is an atherosclerotic disease that often results in major cardiovascular events. This study aimed to prospectively examine the potential of urine NGAL (uNGAL) in predicting worsening PAD status and major adverse limb events (MALE). Baseline urine NGAL (uNGAL) and urine creatinine (uCr) concentrations were measured in PAD (n = 121) and non-PAD (n = 77) patients. Levels of uNGAL were normalized for urine creatinine (uNGAL/uCr). Outcomes included worsening PAD status, which was defined as a drop in ankle brachial index (ABI) > 0.15, and major adverse limb events (MALE), which was defined as a need for surgical revascularization or amputations. PAD patients had 2.30-fold higher levels of uNGAL/uCr [median (IQR) 31.8 (17.0-62.5) µg/g] in comparison to non-PAD patients [median (IQR) 73.3 (37.5-154.7) µg/g] (P = 0.011). Multivariate cox analysis showed that uNGAL/uCr levels were independently associated with predicting worsening PAD status and MALE outcomes. Cumulative survival analysis, over follow up period, demonstrated a direct correlation between elevated uNGAL/uCr levels and PAD disease progression and MALE outcomes. These data demonstrate an association between elevated uNGAL/uCr levels and worsening PAD disease status and MALE outcomes, indicating its potential for risk-stratification of PAD patients.
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Lesión Renal Aguda , Enfermedades Cardiovasculares , Lipocalina 2 , Enfermedad Arterial Periférica , Lesión Renal Aguda/orina , Proteínas de Fase Aguda , Biomarcadores/orina , Enfermedades Cardiovasculares/orina , Creatinina/orina , Humanos , Lipocalina 2/orina , Enfermedad Arterial Periférica/orina , Proteínas Proto-Oncogénicas/orinaRESUMEN
BACKGROUND: Acute kidney injury (AKI), a frequent and serious complication of hospitalized patients, is associated with increased mortality and morbidity. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early identification of AKI. We report a comparative laboratory verification of the Abbott Diagnostics (ARCHITECT® urine NGAL) and BioPorto Diagnostics (NGAL TestTM) assays including an assessment of the Abbott assay's performance in EDTA plasma. METHODS: Intra-/interbatch imprecision, linearity, recovery, and limit of quantitation (LoQ) were assessed and an interassay comparison performed (n = 51). Between-laboratory agreement was assessed against other laboratories using the Abbott (n = 48) and BioPorto (n = 94) assays. Plasma NGAL (pNGAL) levels were measured in non-AKI patients with a range of estimated glomerular filtration rates (n = 80). RESULTS: Coefficients of variation (CVs) for intra- and interbatch imprecision were 0.7%-12.4% and 1.9%-27.5% for the BioPorto assay, respectively, and 1.4%-6.3%/3.4%-6.8%, respectively, for the Abbott assay. The BioPorto assay exhibited a higher LoQ (27.5 ng/mL vs 1.2 ng/mL). Both assays were linear over the range 5-6000 ng/mL. Recovery of recombinant NGAL was 113.1 ± 7.1% and 96.5 ± 7.8% for the Abbott and BioPorto assays, respectively. On average, the Abbott assay gave results 9.2% lower than the BioPorto assay. Mean differences of 0.2% (Abbott) and 20.2% (BioPorto) were observed in the between-laboratory comparison. In patients without AKI, pNGAL levels were inversely proportional to eGFR. CONCLUSIONS: Performance of the Abbott and BioPorto assays was similar although the latter performed less well at lower NGAL concentrations. The Abbott assay tended to yield lower results, exhibited a lower LoQ and over-recovered NGAL. Although only Conformité Européenne-marked and marketed for use in urine, the Abbott assay demonstrated equivalent performance to the BioPorto assay with EDTA plasma.
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Lesión Renal Aguda , Lipocalinas , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Proteínas de Fase Aguda/orina , Ácido Edético , Femenino , Humanos , Inmunoensayo , Lipocalina 2 , Lipocalinas/orina , Masculino , Proteínas Proto-Oncogénicas/orinaRESUMEN
INTRODUCTION: Chronic kidney disease (CKD) is a prevalent complication of sickle cell anemia (SCA). Hyperfiltration that delayed detection of CKD is common in SCA patients. Identification of novel urinary biomarkers correlating with glomerular filtration rates may help to detect and predict progression of renal disease. METHODS: Reanalysis of mass spectra of urinary samples obtained from University of Illinois at Chicago identified kringle domain-containing protein HGFL. RESULTS: HGFL levels correlated with hyperfiltration, were significantly reduced at CKD stage 1 compared to stage 0, negatively correlated with progression of CKD and were suitable for differentiation of stage 1. Better prediction of CKD progression to stage 2 was observed for HGFL-based risk prediction compared to the estimated glomerular filtration rate (eGFR)-based prediction. Results from a Howard University patient cohort supported the utility of HGFL-based test for the differentiation of stage 1 of CKD. CONCLUSION: Urinary HGFL may contribute additional information beyond eGFR and improve diagnosis of early-stage CKD in SCA patients.
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Anemia de Células Falciformes/complicaciones , Factor de Crecimiento de Hepatocito/orina , Proteínas Proto-Oncogénicas/orina , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/orina , Adolescente , Adulto , Anciano , Biomarcadores/orina , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Tasa de Filtración Glomerular , Factor de Crecimiento de Hepatocito/química , Humanos , Kringles , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas/química , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/fisiopatología , Adulto JovenRESUMEN
Mechanical stimulations can prevent bone loss, but their effects on the tumor-invaded bone or solid tumors are elusive. Here, we evaluated the effect of knee loading, dynamic loads applied to the knee, on metastasized bone and mammary tumors. In a mouse model, tumor cells were inoculated to the mammary fat pad or the proximal tibia. Daily knee loading was then applied and metabolic changes were monitored mainly through urine. Urine samples were also collected from human subjects before and after step aerobics. The result showed that knee loading inhibited tumor progression in the loaded tibia. Notably, it also reduced remotely the growth of mammary tumors. In the urine, an altered level of cholesterol was observed with an increase in calcitriol, which is synthesized from a cholesterol derivative. In urinary proteins, knee loading in mice and step aerobics in humans markedly reduced WNT1-inducible signaling pathway protein 1, WISP1, which leads to poor survival among patients with breast cancer. In the ex vivo breast cancer tissue assay, WISP1 promoted the growth of cancer fragments and upregulated tumor-promoting genes, such as Runx2, MMP9, and Snail. Collectively, the present preclinical and human study demonstrated that mechanical stimulations, such as knee loading and step aerobics, altered urinary metabolism and downregulated WISP1. The study supports the benefit of mechanical stimulations for locally and remotely suppressing tumor progression. It also indicated the role of WISP1 downregulation as a potential mechanism of loading-driven tumor suppression.
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Neoplasias Óseas/terapia , Neoplasias de la Mama/terapia , Proteínas CCN de Señalización Intercelular/metabolismo , Terapia por Ejercicio , Neoplasias Mamarias Experimentales/terapia , Condicionamiento Físico Animal , Proteínas Proto-Oncogénicas/metabolismo , Animales , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Proteínas CCN de Señalización Intercelular/orina , Línea Celular Tumoral , Colesterol/orina , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas/orinaRESUMEN
Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (CysC), uromodulin (UMOD), and some interleukins (IL-6 and IL-18) can be considered as diagnostic markers of acute kidney injury (AKI). The aim of this study was to verify the applicability of four urinary (u) markers, namely uNGAL, uKIM-1, uCysC, and uUMOD, for the diagnosis of ascending AKI induced by bacterial pyelonephritis. The study included 30 female rats that were divided into three groups (n = 10 each) and were inoculated transurethrally with various doses of Escherichia coli to induce isolated pyelonephritis (group 1, 105 CFU/ml), pyelonephritis-induced AKI (group 2, 107 CFU/ml), or AKI and urosepsis (group 3, 109 CFU/ml). The inoculate contained a highly virulent E. coli strain isolated from a patient with pyelonephritis. Urine samples were obtained prior to the inoculation and 7, 14, and 21 days thereafter. The concentrations of all assessed proteins were determined in the urine samples by ELISA. All the study groups showed elevated concentrations of uNGAL and uCysC at all study time points. The concentrations of uKIM-1 in group 1 were the same as that at the baseline, whereas it was elevated in groups 2 and 3 at all study time points. The concentrations of uUMOD in groups 1 and 2 tended to decrease with the time from inoculation, whereas it rapidly increased in group 3 at 21 days postinfection. uKIM-1 seems to be the only marker of ascending AKI associated with urinary tract infection. Elevated concentrations of uNGAL, uCysC, and uUMOD were found in both AKI and isolated pyelonephritis. Thus, it can be concluded that none of these markers can be used as a single diagnostic marker of ascending AKI, as it may produce false-negative results, leading to incorrect diagnosis, lack of adequate treatment, and increased mortality risk.
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Lesión Renal Aguda/orina , Proteínas de Fase Aguda/orina , Moléculas de Adhesión Celular/orina , Cistatina C/orina , Lipocalinas/orina , Proteínas Proto-Oncogénicas/orina , Pielonefritis/orina , Uromodulina/orina , Lesión Renal Aguda/etiología , Animales , Biomarcadores/orina , Modelos Animales de Enfermedad , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/orina , Femenino , Lipocalina 2 , Pielonefritis/complicaciones , Ratas WistarRESUMEN
BACKGROUND: Hemolysis during cardiopulmonary bypass may lead to acute kidney injury caused by an excessive amount of iron. The clinical usefulness of the measurement of total iron concentration in the urine with the use of the atomic absorption spectrometry method for early identification of patients with postoperative acute kidney injury is not well-established. OBJECTIVES: An observational, prospective study was conducted on a group of 88 pre-selected adult patients undergoing a planned coronary artery bypass grafting (CABG) procedure. MATERIAL AND METHODS: The amount and concentrations of total iron, creatinine and neutrophil gelatinaseassociated lipocalin (NGAL) were evaluated in urine samples. A comparative analysis of the evaluated biochemical parameters was performed in regard to the occurrence of acute kidney injury 48 h postoperatively. RESULTS: Patients in the acute kidney injury group presented more advanced age (p = 0.01), preoperative myocardial infarction (p = 0.02), diuresis reduction (p = 0.04), and lower total iron levels in the 48-hour urine sample (p = 0.01). There was no difference when considering iron concentration in single urine samples in the study group. CONCLUSIONS: The sole result of total iron concentration in single urine samples is unreliable for the diagnosis of acute kidney injury after cardiac surgery. Decreased excretion of iron in the urine seems to be an important additional element in the multifactorial pathogenesis of acute postoperative kidney failure.
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Lesión Renal Aguda/etiología , Proteínas de Fase Aguda/orina , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Creatinina/sangre , Hierro/orina , Lipocalina 2/orina , Proteínas Proto-Oncogénicas/orina , Lesión Renal Aguda/sangre , Lesión Renal Aguda/orina , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Puente Cardiopulmonar/efectos adversos , Humanos , Pruebas de Función Renal , Lipocalina 2/sangre , Lipocalina 2/metabolismo , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/orina , Valor Predictivo de las Pruebas , Estudios Prospectivos , Proteínas Proto-Oncogénicas/sangreRESUMEN
PURPOSE: To determine the optimal time interval of repeated intravenous injections of iodixanol in rat model and to identify the injury location and causes of renal damage in vivo. MATERIALS AND METHODS: Rats were randomly divided into Control group, Group 1 with one iodixanol injection, and Group 2 with two iodixanol injections. Group 2 was subdivided into 3 cohorts according to the interval between the first and second iodixanol injections as 1, 3, and 5 days, respectively. Blood oxygen level-dependent (BOLD) imaging and diffusion weighted imaging (DWI) were performed at 1 hour, 1 day, 3 days, 5 days, and 10 days after the application of solutions. RESULTS: Compared with Group 1 (7.2%), Group 2 produced a remarkable R2â increment at the inner stripe of the renal outer medulla by 15.37% (P = 0.012), 14.83% (P = 0.046), and 13.53% (P > 0.05), respectively, at 1 hour after repeated injection of iodixanol. The severity of BOLD MRI to detect renal hypoxia was consistent with the expression of HIF-1α and R2â was well correlated with HIF-1α expression (r = 0.704). The acute tubular injury was associated with urinary NGAL and increased significantly at 1 day. CONCLUSIONS: Repetitive injection of iodixanol within a short time window can induce acute kidney injury, the impact of which on renal damage in rats disappears gradually 3-5 days after the injections.
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Inyecciones , Riñón/fisiopatología , Imagen por Resonancia Magnética , Ácidos Triyodobenzoicos/administración & dosificación , Ácidos Triyodobenzoicos/farmacología , Proteínas de Fase Aguda/orina , Animales , Creatinina/sangre , Imagen de Difusión por Resonancia Magnética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Procesamiento de Imagen Asistido por Computador , Riñón/efectos de los fármacos , Riñón/patología , Lipocalina 2 , Lipocalinas/orina , Masculino , Oxígeno/sangre , Proteínas Proto-Oncogénicas/orina , Ratas Wistar , Factores de TiempoRESUMEN
PURPOSE: Neutrophil gelatinase-associated lipocalin (NGAL) levels in the serum and urine are predictive biomarkers of acute kidney injury with correlation to complication and survival in major surgery. Salivary levels of NGAL during acute renal colic may reflect the degree of renal injury as it appears in different compartments encompassing body response in time perspective. Our aim is to evaluate and examine the feasibility and correlation of salivary NGAL with serum and urine levels in acute renal colic event. MATERIALS AND METHODS: A prospective controlled study of all patients presenting to the emergency room with acute renal colic event diagnosed with single ureteral stone obstruction by noncontrast CT. Saliva, urine, and blood samples were collected in patients and a control group during the first morning of admission. RESULTS: The study groups consisted of 44 patients and 13 controls, mean age 47 ± 15 years, body mass index 29 ± 6, mean stone size 6 ± 4 mm, mean creatinine levels 1.3 ± 0.7 mg/dL, mean white blood count 10,900 ± 3100 counts per field, and C-reactive protein 29 ± 55. Serum (190 ± 120 ng/mL vs 81 ± 24; p < 0.001) and predominantly salivary (474 ± 185 vs 328 ± 134 ng/mL; p < 0.05) NGAL levels were significantly elevated in patients compared with controls. CONCLUSIONS: Salivary NGAL sampling is feasible during the acute phase of renal colic. High levels of salivary NGAL are observed in a single sampling during acute ureteral stone obstruction and may advance clinical decision-making.
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Cálculos Renales/metabolismo , Lipocalina 2/análisis , Cólico Renal/metabolismo , Saliva/química , Lesión Renal Aguda/etiología , Proteínas de Fase Aguda/orina , Adulto , Anciano , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Creatinina/sangre , Estudios de Factibilidad , Femenino , Humanos , Lipocalinas/orina , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Proto-Oncogénicas/orina , Obstrucción Ureteral/metabolismoRESUMEN
Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high-salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high-salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high-salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0.8% NaCl) or salt-loaded (2, 4, and 8% NaCl) diet from 9 to 17 weeks of age. A urine sample was obtained once a week and urinary vanin-1, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (Kim-1) were measured. At 17 weeks of age, 8% salt-loaded WKY showed histopathological renal tubular damage and elevated Rac1 activity in renal tissues. Although there was no significant increase in serum creatinine, urinary albumin, N-acetyl-ß-D-glucosaminidase (NAG), or Kim-1 during the study period among the groups, urinary vanin-1 and NGAL significantly increased in 8% salt-loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin-1 and NGAL, which might be induced by salt per se, are potentially earlier biomarkers for renal tubular damage in normotensive rats under a high-salt intake.
Asunto(s)
Presión Sanguínea/fisiología , Enfermedades Renales/inducido químicamente , Túbulos Renales/patología , Cloruro de Sodio Dietético/toxicidad , Cloruro de Sodio/toxicidad , Proteínas de Fase Aguda/orina , Envejecimiento , Alimentación Animal , Animales , Biomarcadores/orina , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Lipocalina 2 , Lipocalinas/orina , Proteínas Proto-Oncogénicas/orina , Ratas , Ratas Endogámicas WKY , Cloruro de Sodio/administración & dosificación , Cloruro de Sodio Dietético/administración & dosificaciónRESUMEN
BACKGROUND: The pharmacological blockade of galectin-3 (Gal-3), a ß-galactoside-binding lectin, reduces renal impairment in acute kidney injury, hyperaldosteronism or nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in renal damage in spontaneously hypertensive rats (SHRs). METHODS AND RESULTS: Gal-3 inhibition did not modify blood pressure levels in 30-week-old SHR. Kidney weight was higher in SHR, with no effect of MCP treatment (100âmg/kg/day in the drinking water). Plasma creatinine and albuminuria were slightly but significantly increased in SHR and reduced by MCP, as well as plasma and urinary neutrophil gelatinase-associated lipocalin. In kidney from SHR, Gal-3 was upregulated, as well as the fibrotic markers (collagen type I, TGF-ß and connective tissue growth factor) and tubulointerstitial fibrosis. MCP treatment reduced Gal-3 levels and fibrosis. The epithelial-mesenchymal transition (EMT) molecules (fibronectin, α-smooth muscle actin and ß-catenin) were modified in SHR and normalized by Gal-3 inhibition. The inflammatory mediators (monocyte chemoattractant protein-1, osteopontin, cd68, cd80, cd44 and cd45) were elevated in SHR and attenuated by MCP. Renal damage markers (neutrophil gelatinase-associated lipocalin and kidney injury molecule-1) were augmented in SHR and improved by MCP. In renal epithelial normal rat kidney-52E cells, Gal-3 treatment induced EMT markers, whereas Gal-3 silencing attenuated EMT. CONCLUSION: Gal-3 inhibition attenuated early renal damage in SHR as indicated by reduced albuminuria, improved renal function and decreased renal fibrosis, EMT and inflammation, independently of blood pressure levels. These data suggest that Gal-3 could be a potential therapeutic candidate for the prevention of early renal alterations in hypertension.
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Antígenos CD/metabolismo , Galectina 3/antagonistas & inhibidores , Hipertensión/tratamiento farmacológico , Enfermedades Renales/prevención & control , Riñón/patología , Pectinas/farmacología , Actinas/metabolismo , Lesión Renal Aguda , Proteínas de Fase Aguda/orina , Albuminuria/tratamiento farmacológico , Animales , Presión Sanguínea , Línea Celular , Quimiocina CCL2/metabolismo , Colágeno Tipo I/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Creatinina/sangre , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibronectinas/metabolismo , Fibrosis , Hipertensión/complicaciones , Enfermedades Renales/etiología , Enfermedades Renales/patología , Lipocalina 2 , Lipocalinas/sangre , Lipocalinas/orina , Masculino , Tamaño de los Órganos , Osteopontina/metabolismo , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/orina , Ratas , Ratas Endogámicas SHR , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba , beta Catenina/metabolismoRESUMEN
TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM.
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Nefropatías Diabéticas/metabolismo , Proteína S/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Femenino , Humanos , Glomérulos Renales/metabolismo , Masculino , Persona de Mediana Edad , Proteína S/orina , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/orina , Proteínas Tirosina Quinasas Receptoras/sangre , Proteínas Tirosina Quinasas Receptoras/orina , Tirosina Quinasa c-Mer , Tirosina Quinasa del Receptor AxlRESUMEN
Neonatal kidney injury is a frequent pathology, especially among premature infants. The search for effective nephroprotection requires the creation of adequate experimental models of nephropathy in newborns. In this study, we explored the development of acute kidney injury (AKI) in neonatal rats during hypoxia or administration of endotoxin. We found that 2-h hypoxia (8% O2 ) and the intraperitoneal injection of 4 mg·kg-1 lipopolysaccharide (LPS) causes the appearance of AKI markers, such as kidney injury molecule-1 (ÐIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the rat urine after 24 and 72 h of exposure. On the other hand, the levels of blood urine nitrogen under the same conditions rise only slightly. The damaging effects of hypoxia and endotoxin were accompanied by histological changes in the renal tissue and a significant decrease in the proliferation marker, (proliferating cell nuclear antigen). It is revealed that 3 h after the introduction of LPS, levels of reactive oxygen species in the kidney were significantly increased, and the injection of the antioxidant N-acetylcysteine afforded protection from AKI, evaluated by urine ÐIM-1 and NGAL levels. Thus, the simulation of AKI in newborn rat pups can be employed in screening for potential nephroprotective drugs, particularly among antioxidative compounds to be used in neonatology.
Asunto(s)
Lesión Renal Aguda/genética , Proteínas de Fase Aguda/genética , Moléculas de Adhesión Celular/genética , Hipoxia/genética , Lipocalinas/genética , Proteínas Proto-Oncogénicas/genética , Especies Reactivas de Oxígeno/metabolismo , Acetilcisteína/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Lesión Renal Aguda/prevención & control , Proteínas de Fase Aguda/orina , Animales , Animales Recién Nacidos , Antioxidantes/farmacología , Biomarcadores/orina , Nitrógeno de la Urea Sanguínea , Moléculas de Adhesión Celular/orina , Modelos Animales de Enfermedad , Expresión Génica , Humanos , Hipoxia/patología , Lactante , Lipocalina 2 , Lipocalinas/orina , Lipopolisacáridos , Estrés Oxidativo/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Proto-Oncogénicas/orina , Ratas , Especies Reactivas de Oxígeno/antagonistas & inhibidoresRESUMEN
The association between pediatric cardiac surgery, acute kidney injury (AKI), and clinical outcomes has been studied several times in the recent literature. In this issue of Critical Care an interesting and original study analyzed the path from causal AKI entities to clinical AKI consequences through the application of structural equation modeling. The authors described the complex connections linking duration of cardiopulmonary bypass, cross clamp-time, and descriptors of low cardiac output syndrome to AKI modeled as a complex variable composed of post-operative serum creatinine increase of 50 % over baseline, urine output <0.5 ml/kg/h, and urine creatinine-normalized neutrophil gelatinase lipocalin within 12 h of surgery. Similarly, the causal relationships between AKI and hard outcomes in the analyzed population were verified and quantified. The authors, for the first time, produce a repeatable coefficient (0.741) that may become a useful quality benchmark and could be applied to test future interventions aiming to reduce the burden of AKI on children's clinical course.