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BACKGROUND: Renal dysfunction is a common complication following liver transplantation (LT). This study aimed to determine whether a comprehensive assessment of kidney function using nineteen serum and urinary biomarkers (BMs) within the first 48 h post-LT could enhance the prediction of severe acute kidney injury (AKI) and the need of kidney replacement therapy (KRT) during the first postoperative week. METHODS: Blood and urine (U) samples were collected during the pre- and postoperative periods. Nineteen BMs were evaluated to assess kidney health in the first 48 h after LT. Classification and regression tree (CART) cross-validation identified key predictors to determine the best BM combination for predicting outcomes. RESULTS: Among 100 LT patients, 36 developed severe AKI, and 34 required KRT within the first postoperative week. Preoperative assessment of U neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) predicted the need for KRT with 75% accuracy. The combined assessment of U osmolality (OSM), U kidney injury molecule 1 (KIM-1), and tissue inhibitor of metalloproteinase (TIMP-1) within 48 h post-LT predicted severe AKI with 80% accuracy. U-OSM alone, measured within 48 h post-LT, had an accuracy of 83% for predicting KRT need, outperforming any BM combination. CONCLUSIONS: Combined BM analysis can accurately predict severe AKI and KRT needs in the perioperative period of LT. U-OSM alone proved to be an effective tool for monitoring the risk of severe AKI, available in most centers. Further studies are needed to assess its impact on AKI progression postoperatively.Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title 'Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)' and identifier NCT02095431.
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Lesión Renal Aguda , Biomarcadores , Lipocalina 2 , Trasplante de Hígado , Terapia de Reemplazo Renal , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Lesión Renal Aguda/sangre , Lesión Renal Aguda/terapia , Trasplante de Hígado/efectos adversos , Biomarcadores/sangre , Biomarcadores/orina , Masculino , Femenino , Persona de Mediana Edad , Lipocalina 2/orina , Lipocalina 2/sangre , Adulto , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Receptor Celular 1 del Virus de la Hepatitis A/sangre , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Anciano , Proteínas de Unión a Ácidos Grasos/sangre , Proteínas de Unión a Ácidos Grasos/orina , Inhibidor Tisular de Metaloproteinasa-1/sangre , Estudios Prospectivos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Valor Predictivo de las PruebasRESUMEN
Development of efficient portable sensors for accurately detecting biomarkers is crucial for early disease diagnosis, yet remains a significant challenge. To address this need, we introduce the enhanced luminescence lateral-flow assay, which leverages highly luminescent upconverting nanoparticles (UCNPs) alongside a portable reader and a smartphone app. The sensor's efficiency and versatility were shown for kidney health monitoring as a proof of concept. We engineered Er3+- and Tm3+-doped UCNPs coated with multiple layers, including an undoped inert matrix shell, a mesoporous silica shell, and an outer layer of gold (UCNP@mSiO2@Au). These coatings synergistically enhance emission by over 40-fold and facilitate biomolecule conjugation, rendering UCNP@mSiO2@Au easy to use and suitable for a broad range of bioapplications. Employing these optimized nanoparticles in lateral-flow assays, we successfully detected two acute kidney injury-related biomarkersâkidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)âin urine samples. Using our sensor platform, KIM-1 and NGAL can be accurately detected and quantified within the range of 0.1 to 20 ng/mL, boasting impressively low limits of detection at 0.28 and 0.23 ng/mL, respectively. Validating our approach, we analyzed clinical urine samples, achieving biomarker concentrations that closely correlated with results obtained via ELISA. Importantly, our system enables biomarker quantification in less than 15 min, underscoring the performance of our novel UCNP-based approach and its potential as reliable, rapid, and user-friendly diagnostics.
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Biomarcadores , Oro , Receptor Celular 1 del Virus de la Hepatitis A , Lipocalina 2 , Nanopartículas , Humanos , Biomarcadores/orina , Lipocalina 2/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Oro/química , Nanopartículas/química , Erbio/química , Lesión Renal Aguda/orina , Lesión Renal Aguda/diagnóstico , Dióxido de Silicio/química , Tulio/química , Mediciones Luminiscentes/métodos , Luminiscencia , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Límite de DetecciónRESUMEN
Environmental exposure to heavy metals and metalloids, originating from sources such as mining and manufacturing activities, has been linked to adverse renal effects. This cross-sectional study assessed children's exposure to these elements and its association with urinary kidney injury molecule-1 (KIM-1). We analyzed data from 99 school-aged children residing in nine localities within the state of Colima, Mexico, during the latter half of 2023. Levels of 23 metals/metalloids and urinary KIM-1 were measured using inductively coupled plasma mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay, respectively. Detectable levels of these contaminants were found in over 91% of participants, with varied exposure profiles observed across locations ( p = 0.019). After adjusting for confounding factors like gender, age, and locality, higher levels of six metals/metalloids (boron, cadmium, cesium, lithium, selenium, zinc) were significantly associated with increased KIM-1 levels. Tailored mitigation efforts are crucial to protect children from regional pollutant burdens. However, limitations exist, as our study did not capture all potential factors influencing heavy metal/metalloid and KIM-1 levels.
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Exposición a Riesgos Ambientales , Receptor Celular 1 del Virus de la Hepatitis A , Metales Pesados , Humanos , Niño , Femenino , Masculino , Estudios Transversales , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Metales Pesados/análisis , Metales Pesados/orina , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/efectos adversos , México , Metaloides/orina , Metaloides/análisis , Contaminantes Ambientales/análisis , Contaminantes Ambientales/orina , AdolescenteRESUMEN
Aim: To evaluate the prediction capacity of urinary biomarkers for death in critically ill patients with COVID-19. Methods: This is a prospective study with critically ill patients due to COVID-19 infection. The urinary biomarkers NGAL, KIM-1, MCP-1 and nephrin were quantified on ICU admission. Results: There was 40% of death. Urinary nephrin and MCP-1 had no association with death. Tubular biomarkers (proteinuria, NGAL and KIM-1) were predictors of death and cut-off values of them for death were useful in stratify patients with worse prognosis. In a multivariate cox regression analysis, only NGAL remains associated with a two-mount survival chance. Conclusion: Kidney tubular biomarkers, mostly urinary NGAL, had useful capacity to predict death in critically ill COVID-19 patients.
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Lesión Renal Aguda , COVID-19 , Lesión Renal Aguda/diagnóstico , Biomarcadores , Enfermedad Crítica , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Lipocalina 2 , Estudios ProspectivosRESUMEN
INTRODUCTION: Amphotericin B (AmB), used for systemic fungal infections, has a limited clinical application because of its high nephrotoxicity. Natural antioxidant and anti-inflammatory substances have been widely studied for protection against drug-induced nephrotoxicity. α-Bisabolol (BIS) has demonstrated a nephroprotective effect on both in vitro and in vivo models. AIMS: The aim of this work was to evaluate the effect of BIS against AmB-induced nephrotoxicity in vitro. MATERIAL AND METHODS: LLC-MK2 cells were pre- and post-treated with non-toxic BIS concentrations and/or AmB IC50 (13.97 µM). Cell viability was assessed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] assay. Flow cytometry analyses were used to assess cell death mechanism, production of reactive oxidative stress (ROS) and mitochondrial transmembrane potential. Kidney Injury Molecule-1 (KIM-1) levels were measured via ELISA. KEY FINDINGS: The present work showed that BIS pretreatment (125; 62.5 and 31.25 µM) increased cell viability when compared to the group treated only with AmB IC50. AmB treatment induced both necrosis (7-AAD-labeled cells) and late apoptosis (AnxV-labeled). BIS was able to prevent the occurrence of these events. These effects were associated with a decrease of ROS accumulation, improving transmembrane mitochondrial potential and protecting against tubular cell damage, highlighted by the inhibition of KIM-1 release after BIS treatment. SIGNIFICANCE: BIS presented a potential effect on model of renal cytotoxicity induced by AmB, bringing perspectives for the research of new nephroprotective agents.
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Supervivencia Celular/efectos de los fármacos , Túbulos Renales Proximales/efectos de los fármacos , Sesquiterpenos Monocíclicos/farmacología , Anfotericina B/farmacología , Anfotericina B/toxicidad , Animales , Antifúngicos/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Riñón/metabolismo , Túbulos Renales Proximales/metabolismo , Macaca mulatta , Sesquiterpenos Monocíclicos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacologíaRESUMEN
OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.
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Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/terapia , Biomarcadores/orina , Cistatina C/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Recién Nacido , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Interleucina-18/orina , Lipocalina 2/orina , Masculino , Estudios Prospectivos , Inhibidor Tisular de Metaloproteinasa-2/orina , Vasoconstrictores/administración & dosificaciónRESUMEN
To investigate the role of TYRO3, AXL and TIM1 receptors in the Zika virus (ZIKV) cycle, we determined their mRNA expression in different placental sites of ZIKV infected tissue during pregnancy. Unexpectedly, the ZIKV infection was not related with mRNA upregulation of these receptors or changes in expression of type I and III interferons in different placental sites. Instead, a decrease of TYRO3 mRNA expression was observed in positive sites of ZIKV positive placentas in comparison to negative sites. The basis of this downregulation can help to understand how ZIKV persists in placental tissue during pregnancy.
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Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Placenta/enzimología , Complicaciones Infecciosas del Embarazo/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Infección por el Virus Zika/metabolismo , Estudios de Casos y Controles , Femenino , Interacciones Huésped-Patógeno , Humanos , Interferón Tipo I/metabolismo , Interferones/metabolismo , Placenta/inmunología , Placenta/virología , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/virología , Virus Zika/fisiología , Infección por el Virus Zika/inmunología , Interferón lambda , Tirosina Quinasa del Receptor AxlRESUMEN
Sickle cell disease (SCD) is a hereditary condition characterized by homozygosis of the hemoglobin S (HbS) gene. Marked morbimortality is observed due to chronic hemolysis, endothelial injury, and episodes of vaso-occlusion, which leads to multi-organ damage. Renal impairment is common and may have different presentations, such as deficiency in urinary acidification or concentration, glomerulopathies, proteinuria, and hematuria, frequently resulting in end-stage renal disease (ESRD). Novel biomarkers of renal function, such as kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein 1 (MCP-1) are being studied in order to enable early diagnosis of kidney damage in SCD.
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Anemia de Células Falciformes/orina , Quimiocina CCL2/orina , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Fallo Renal Crónico/orina , Riñón/metabolismo , Lipocalina 2/orina , Anemia de Células Falciformes/complicaciones , Biomarcadores/orina , Humanos , Fallo Renal Crónico/etiologíaRESUMEN
BACKGROUND: Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. RESULTS: Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations ≥ 6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). CONCLUSIONS: High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/sangre , Ácido Úrico/sangre , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Creatinina/orina , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Interleucinas/orina , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/orinaRESUMEN
Acute Kidney Injury (AKI) is associated with high morbidity and mortality. Ischemia and reperfusion (I/R) are events that lead to AKI through hypoxia, reactive oxygen species (ROS) production, oxidative stress and apoptosis. We aimed to evaluate the mechanism of nephroprotection mediated by Bisabolol in human tubular kidney cells after injury by I/R in vitro. HK2 cells were exposed to I/R and treated with Bisabolol. Cell viability was accessed by MTT assay. Cells were submitted to flow cytometry to evaluate necrotic/apoptotic cells, reactive oxygen species production and mitochondrial transmembrane depolarization. TBARS and GSH were used as parameters of redox balance. Also, KIM-1 supernatant levels were measured. In order to identify an interaction between bisabolol and NOX4, molecular docking and enzymatic assays were performed. Expression of isoform NOX4 on treated cells was examined by western-blot. Finally, cells were visualized by scanning electron microscopy. Bisabolol improved cell viability and prevented cell death by apoptosis, indicated also by the decreased levels of KIM-1. It was observed a decrease on reactive oxygen species production and mitochondrial depolarization, with antioxidant regulation by increased GSH and decreased lipid peroxidation. It was also demonstrated that bisabolol treatment can inhibit NOX4. Finally, SEM images showed that bisabolol reduced I/R-induced cell damage. Bisabolol treatment protects HK2 cells against oxidative damage occasioned by I/R. This effect is related to inhibition of apoptosis, decrease on KIM-1 release, reactive oxygen species accumulation and mitochondrial dysfunction. Bisabolol inhibited NOX4 activity in the tubular cells, impairing reactive oxygen species synthesis.
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Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Sesquiterpenos Monocíclicos/farmacología , NADPH Oxidasas/metabolismo , Oxígeno/metabolismo , Daño por Reperfusión/prevención & control , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citoprotección/efectos de los fármacos , Glutatión/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Humanos , Túbulos Renales/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Aflatoxins (AFs) are mycotoxins produced by Aspergillus parasiticus and Aspergillus flavus which frequently contaminate maize. These compounds are considered toxic, especially AFB1 which has been classified as a human carcinogen, due to its relationship with the generation of hepatocellular carcinoma. Studies in vivo, in animal models, prove that chronic consumption of AFB1 has an association with renal adverse effects, but evidence in humans is scarce. Therefore, the main objective of this research was to conduct a pilot study to evaluate the correlation between exposure to AFB1 and early-stage renal damage in indigenous women of San Luis Potosí, Mexico. Exposure to AFB1 was measured through the biomarker AFB1-lysine and renal damage through kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin-C (Cys-C). AFB1-Lys was measured by HPLC-FLD. The method was validated with a correlation coefficient of 0.99 and limit of detection and quantification of 3.5 and 4.7 pg mL-1, respectively. Levels of NGAL, KIM-1, and Cys-C were determined (median (P25-P75), 5.96 (3.16-15.91), 0.137 (0.137-0.281), and 18.49 (5.76-29.57) ng mL-1, respectively). Additionally, glomerular filtration rate (GFR) (83.3 (59.8-107.4) mL/min/1.73 m2) and serum creatinine (SCr) (0.88 (0.72-1.22) mg dL-1) were obtained. The median concentrations for AFB1-Lys were 2.08 (1.89-5.8) pg mg-1 of albumin. Statistically significant correlations between AFB1-Lys/KIM-1 (Rho = 0.498, p = 0.007) and AFB1/Cys-C (Rho = 0.431, p = 0.014) were found. Our results indicate that women are exposed to AFB1, due to the fact that the AFB1-Lys biomarker was found in a high percentage of the study population (83%). In addition, the results of exposure to AFB1 show a strong significant correlation between KIM-1 and Cys-C that may indicate the toxic renal effect. These results are alarming because of the high toxicity of this compound and require adequate intervention to reduce AFB1 exposure in these populations.
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Aflatoxina B1/toxicidad , Biomarcadores/sangre , Carcinógenos/toxicidad , Exposición a Riesgos Ambientales/análisis , Aflatoxina B1/metabolismo , Aflatoxinas , Animales , Carcinógenos/metabolismo , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Riñón , Lipocalina 2 , Masculino , México/etnología , Micotoxinas , Proyectos Piloto , Grupos de PoblaciónRESUMEN
Acute renal failure is one of the most frequent effects observed after taking medicine. Such situations have been tardily discovered, given that existing methods for assessing toxicity are not predictive. In this light, the present work evaluated the effects of gentamicin, a form of nephrotoxic drug, on HK-2 and HEK-293 cells. By using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometry, both cells demonstrated that cytotoxicity occurs in a dose-dependent manner through the processes of apoptosis and cell necrosis. Gene expression analysis showed a relative increase of expression for genes related to cell processes and classic biomarkers, such as TP53, CASP3, CASP8, CASP9, ICAM-1, EXOC3, KIM-1, and CST3. A decrease in expression for genes BCL2L1 and EGF was observed. This study, therefore, indicates that, when the methods are used together, gene expression analysis is able to evaluate the nephrotoxic potential of a substance.
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Antibacterianos/efectos adversos , Apoptosis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Gentamicinas/efectos adversos , Riñón/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Alternativas al Uso de Animales , Biomarcadores Farmacológicos/metabolismo , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Cistatina C/agonistas , Cistatina C/genética , Cistatina C/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Factor de Crecimiento Epidérmico/antagonistas & inhibidores , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento Epidérmico/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica , Receptor Celular 1 del Virus de la Hepatitis A/agonistas , Receptor Celular 1 del Virus de la Hepatitis A/genética , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Humanos , Concentración 50 Inhibidora , Interleucina-18/antagonistas & inhibidores , Interleucina-18/genética , Interleucina-18/metabolismo , Riñón/metabolismo , Riñón/patología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , NecrosisRESUMEN
Acute kidney injury (AKI) is one of the most important complications of bothropic poisoning and its early identification remains challenging. The nephrotoxicity of Bothrops insularis venom (BinsV) was previously described by our research group. In this study, we continued to evaluate the effect of BinsV on kidney function in mice and LLC-MK2 proximal tubule cells, evaluating KIM-1 protein as an early AKI biomarker. Male Swiss mice were inoculated with BinsV intramuscularly and observed for 24â¯h in a metabolic cage model. Urine and blood were collected for biochemical analyses and the kidneys were examined for oxide-reducing balance and submitted to histological analysis. LLC-MK2 cells incubated with BinsV were assessed for cell viability and cell death mechanism by flow cytometry. Histological analysis of the kidneys indicated AKI and the oxide-reducing analyses demonstrated a decreasing in reduced glutathione (GSH) levels and an increasing on Malondialdehyde (MDA) levels. BinsV was cytotoxic to LLC-MK2 and the cytometry analyses suggested necrosis. Within 24â¯h after the envenomation, urinary creatinine did not increase, but the urinary levels of KIM-1 increased. In conclusion, we found AKI evidence in the kidney tissue and the increase in the KIM-1 levels suggest it can be used as an early AKI biomarker.
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Lesión Renal Aguda/inducido químicamente , Venenos de Crotálidos/toxicidad , Receptor Celular 1 del Virus de la Hepatitis A/sangre , Mordeduras de Serpientes/sangre , Lesión Renal Aguda/sangre , Animales , Biomarcadores/sangre , Bothrops , Regulación de la Expresión Génica/efectos de los fármacos , Glutatión/sangre , Ratones , Especies Reactivas de Oxígeno , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
INTRODUCTION AND AIM: HAVCR1 protein is the cellular receptor for hepatitis A virus (HAV). Genetic polymorphism in this gene may alter the outcome of HAV infection. In a previous study, a 6-amino acid insertion (157insMTTTVP) in HAVCR1 gene was associated with more severe disease. We decided to investigate this association further. MATERIAL AND METHODS: We sequenced exon 4 of the HAVCR1 gene in patients with clinical hepatitis A attending our institution, and a group of healthy controls in a disease-endemic setting in India. Frequencies of different haplotypes of a genomic region with two overlapping insertion-deletion polymorphisms (indels; rs141023871 and rs139041445) were compared between patients and controls, as well as between patients with and without a severe form of disease (liver failure). RESULTS: The gene had three haplotypes in the region of interest - a short form, an intermediate-form with a 5-amino acid 157insMTTVP insertion and a long-form with a 6-amino acid 157insMTTTVP insertion. The allele frequency (29/150 [19%] vs. 43/146 [29%]; p = ns) and haplotype frequency (29/75 [39%] vs. 39/73 [53%]; p = ns) of the 157insMTTTVP variant were similar in hepatitis A patients and healthy controls (30%). Further, the allele frequency (12/58 [21%] vs. 17/92 [18%]; p = ns) and haplotype frequency (12/29 [41%] vs.17/46 [37%]; p = ns) of the longest variant were also similar in patients with severe and mild disease. DISCUSSION: In the study population, the 157insMTTTVP variant of HAVCR1 gene was not associated with more severe outcome of HAV infection. Further studies in other populations around the world are needed to assess the relation of this genetic variation with disease outcome.
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Receptor Celular 1 del Virus de la Hepatitis A/genética , Hepatitis A/genética , Mutación INDEL , Polimorfismo Genético , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Enfermedades Endémicas , Exones , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Hepatitis A/diagnóstico , Hepatitis A/epidemiología , Hepatitis A/virología , Virus de la Hepatitis A/patogenicidad , Interacciones Huésped-Patógeno , Humanos , India/epidemiología , Lactante , Masculino , Fenotipo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77â¯years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρâ¯=â¯0.7419, pâ¯<â¯0.0001), with median values of 1.5â¯mg/L and 2⯵g/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55â¯ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15â¯ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ßâ¯=â¯0.56, pâ¯<â¯0.001), Cys-C (ßâ¯=â¯0.022, pâ¯=â¯0.001), KIM-1 (ßâ¯=â¯0.048, pâ¯=â¯0.008), OPN (ßâ¯=â¯0.38, pâ¯=â¯0.041), and eGFR (ßâ¯=â¯0.49, pâ¯=â¯0.03); however, CLU (ßâ¯=â¯0.07, pâ¯=â¯0.100) and TFF-3 (ßâ¯=â¯1.14, pâ¯=â¯0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.
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Arsénico/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Fluoruros/efectos adversos , Enfermedades Renales/inducido químicamente , Riñón/efectos de los fármacos , Contaminantes Químicos del Agua/efectos adversos , Adolescente , Adulto , Anciano , Albuminuria/inducido químicamente , Albuminuria/diagnóstico , Albuminuria/orina , Arsénico/orina , Biomarcadores/orina , Clusterina/orina , Estudios Transversales , Cistatina C/orina , Monitoreo del Ambiente/métodos , Femenino , Fluoruros/orina , Tasa de Filtración Glomerular/efectos de los fármacos , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Enfermedades Renales/diagnóstico , Enfermedades Renales/fisiopatología , Enfermedades Renales/orina , Masculino , México , Persona de Mediana Edad , Osteopontina/orina , Valor Predictivo de las Pruebas , Medición de Riesgo , Factor Trefoil-3/orina , Contaminantes Químicos del Agua/orina , Adulto JovenRESUMEN
Acute kidney injury (AKI) consists of a rapid renal function decline which usually increases serum urea and creatinine levels. Since kidney injury begins by inducing biological and molecular changes which evolve to cellular damage, biomarkers could be used as tools for monitoring early AKI appearance, and predicting its recovery. Among the main AKI biomarkers the neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury molecule-1, monocyte chemotactic peptide-1, N-acetyl-ß-D-glucosaminidase, interleukin-18, liver-type fatty acid-binding protein, netrin-1, cycle arrest markers, endogenous ouabain, selenium-binding protein 1, and BPIFA2 marker, have been described. Even though novel biomarkers seem to be more helpful to early detect AKI and/or predict the need for renal replacement, and mortality compared to serum creatinine, more comprehensive studies are still required to determine their clinical utility.
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Lesión Renal Aguda/sangre , Lesión Renal Aguda/orina , Cistatina C , Proteínas de Unión a Ácidos Grasos , Receptor Celular 1 del Virus de la Hepatitis A , Lipocalina 2 , Acetilglucosaminidasa/orina , Lesión Renal Aguda/diagnóstico , Biomarcadores/sangre , Biomarcadores/orina , Quimiocina CCL2/sangre , Quimiocina CCL2/orina , Cistatina C/sangre , Cistatina C/orina , Proteínas de Unión a Ácidos Grasos/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Interleucina-18/orina , Lipocalina 2/sangre , Lipocalina 2/orina , Inhibidor Tisular de Metaloproteinasa-2/orinaRESUMEN
ABSTRACT Aim: URS is a very commonly used procedure for treatment of ureter stones. Increased hydrostatic pressure in the collecting system linked to fluids used during the procedure may cause harmful effects on the kidney. The aim of this study is to determine whether the URS procedure has a negative effect on the kidney by investigating NGAL, KIM-1, FABP and Cys C levels in urine. Material and Methods: This study included 30 patients undergoing ureterorenoscopy (URS) for ureter stones. Urine samples were collected 5 times; before the URS procedure (control) and at 1, 3, 5 and 12 hours following the procedure. NGAL, KIM-1, FBAP and Cys C levels were measured in urine and compared with the control values. Results: The NGAL levels in urine before the procedure and at 1, 3, 5 and 12 hours after the procedure were 34.59±35.34; 62.72±142.32; 47.15±104.48; 45.23±163.16 and 44.99±60.79ng/mL, respectively (p=0.001). Similarly, the urinary KIM-1, FABP and Cys C levels were found to increase compared to control values; however this increase did not reach statistical significance (p >0.05). Conclusions: After the URS procedure, there were important changes in NGAL, FABP, KIM-1 and Cys C levels. These changes reached statistical significance for NGAL, but did not reach significance for the other parameters. In conclusion, the URS procedure significantly affects the kidney; however, this effect disappears over time.
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Humanos , Masculino , Femenino , Adulto , Anciano , Biomarcadores/orina , Cálculos Ureterales/cirugía , Ureteroscopía/métodos , Persona de Mediana Edad , Cálculos Ureterales/orina , Cistatinas/orina , Ureteroscopía/efectos adversos , Proteínas de Unión a Ácidos Grasos/orina , Lipocalina 2/orina , Receptor Celular 1 del Virus de la Hepatitis A/análisisRESUMEN
AIM: URS is a very commonly used procedure for treatment of ureter stones. Increased hydrostatic pressure in the collecting system linked to fluids used during the procedure may cause harmful effects on the kidney. The aim of this study is to determine whether the URS procedure has a negative effect on the kidney by investigating NGAL, KIM-1, FABP and Cys C levels in urine. MATERIAL AND METHODS: This study included 30 patients undergoing ureterorenoscopy (URS) for ureter stones. Urine samples were collected 5 times; before the URS procedure (control) and at 1, 3, 5 and 12 hours following the procedure. NGAL, KIM-1, FBAP and Cys C levels were measured in urine and compared with the control values. RESULTS: The NGAL levels in urine before the procedure and at 1, 3, 5 and 12 hours after the procedure were 34.59±35.34; 62.72±142.32; 47.15±104.48; 45.23±163.16 and 44.99±60.79ng/mL, respectively (p=0.001). Similarly, the urinary KIM-1, FABP and Cys C levels were found to increase compared to control values; however this increase did not reach statistical significance (p >0.05). CONCLUSIONS: After the URS procedure, there were important changes in NGAL, FABP, KIM-1 and Cys C levels. These changes reached statistical significance for NGAL, but did not reach significance for the other parameters. In conclusion, the URS procedure significantly affects the kidney; however, this effect disappears over time.
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Biomarcadores/orina , Cálculos Ureterales/cirugía , Cálculos Ureterales/orina , Ureteroscopía/métodos , Adulto , Anciano , Cistatinas/orina , Proteínas de Unión a Ácidos Grasos/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Lipocalina 2/orina , Masculino , Persona de Mediana Edad , Ureteroscopía/efectos adversosRESUMEN
BACKGROUND AND OBJECTIVES: We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1.73 m2 were included. Patients with BK virus active nephritis, recurrence of renal disease, GFR decline in previous 3 months, or treated with calcium antagonists or antifungal drugs were excluded. They were randomized to receive placebo (n=10) or eplerenone 25 mg/d for 24 months (n=13). Visits were scheduled at baseline, 6, 12, and 24 months. At each period, a complete clinical examination was performed and blood and urine samples were taken. Urine creatinine, 8-hydroxylated-guanosine, heat shock protein 72 (HSP72), and kidney injury molecule (KIM-1) levels were also assessed. In kidney biopsy samples, the tubulo-interstitial area affected by fibrosis (TIF) and glomerulosclerosis were measured at baseline and after 24 months. RESULTS: The baseline eGFR was 80±6 in the placebo and 86±6 ml/min per 1.73 m2 in the eplerenone group; at 24 months it was 66±8 and 81±7 ml/min per 1.73 m2, respectively (P=0.33; 95% confidence intervals, -18 to 33 at baseline, and -11 to 40 after 24 months). The albumin-to-creatinine ratio was 110±74 in the placebo, and 265±140 mg/g in the eplerenone group; and after 24 months it was 276±140 and 228±88 mg/g, respectively (P=0.15; 95% confidence intervals, -283 to 593, and -485 to 391, respectively). In addition, the placebo exhibited a greater TIF, glomerulosclerosis, and urinary HSP72 compared with the eplerenone group. CONCLUSIONS: Although this study was underpowered to provide definitive evidence that long-term eplerenone administration attenuates the progression of CAN in pediatric transplant patients, it encourages testing the potential benefit of MRB in this pediatric population.
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Glomerulonefritis/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Riñón/efectos de los fármacos , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Espironolactona/análogos & derivados , Adolescente , Factores de Edad , Albuminuria/diagnóstico , Albuminuria/tratamiento farmacológico , Albuminuria/etiología , Aloinjertos , Biomarcadores/orina , Biopsia , Niño , Progresión de la Enfermedad , Esquema de Medicación , Eplerenona , Femenino , Fibrosis , Tasa de Filtración Glomerular/efectos de los fármacos , Glomerulonefritis/diagnóstico , Glomerulonefritis/etiología , Guanosina/análogos & derivados , Guanosina/orina , Proteínas del Choque Térmico HSP72/orina , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Masculino , México , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Estudios Prospectivos , Método Simple Ciego , Espironolactona/administración & dosificación , Espironolactona/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-ß-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.