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1.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206927

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to deterioration of kidney function and end stage kidney disease (ESKD). A number of molecular processes are dysregulated in ADPKD but the exact mechanism of disease progression is not fully understood. We measured protein biomarkers being linked to ADPKD-associated molecular processes via ELISA in urine and serum in a cohort of ADPKD patients as well as age, gender and eGFR matched CKD patients and healthy controls. ANOVA and t-tests were used to determine differences between cohorts. Spearman correlation coefficient analysis was performed to assess coregulation patterns of individual biomarkers and renal function. Urinary epidermal growth factor (EGF) and serum apelin (APLN) levels were significantly downregulated in ADPKD patients. Serum vascular endothelial growth factor alpha (VEGFA) and urinary angiotensinogen (AGT) were significantly upregulated in ADPKD patients as compared with healthy controls. Arginine vasopressin (AVP) was significantly upregulated in ADPKD patients as compared with CKD patients. Serum VEGFA and VIM concentrations were positively correlated and urinary EGF levels were negatively correlated with urinary AGT levels. Urinary EGF and AGT levels were furthermore significantly associated with estimated glomerular filtration rate (eGFR) in ADPKD patients. In summary, altered protein concentrations in body fluids of ADPKD patients were found for the mechanistic markers EGF, APLN, VEGFA, AGT, AVP, and VIM. In particular, the connection between EGF and AGT during progression of ADPKD warrants further investigation.


Assuntos
Rim Policístico Autossômico Dominante/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiotensinogênio/urina , Apelina/sangue , Arginina Vasopressina/sangue , Arginina Vasopressina/urina , Biomarcadores/sangue , Biomarcadores/urina , Fator de Crescimento Epidérmico/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/urina , Fator A de Crescimento do Endotélio Vascular/sangue
2.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204452

RESUMO

Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier-or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.


Assuntos
Biomarcadores/urina , Vesículas Extracelulares/metabolismo , Nefropatias/metabolismo , Animais , Comunicação Celular , Micropartículas Derivadas de Células/metabolismo , Fracionamento Químico , Gerenciamento Clínico , Suscetibilidade a Doenças , Exossomos/metabolismo , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/urina , Biópsia Líquida/métodos , Medicina de Precisão/métodos , Urinálise/métodos
3.
Nutrients ; 13(5)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066958

RESUMO

OBJECTIVE: Dietary intakes must cover protein and essential amino acid (EAA) requirements. For this purpose, different methods have been developed such as the nitrogen balance method, factorial method, or AA tracer studies. However, these methods are either invasive or imprecise, and the Food and Agriculture Organization of the United Nations (FAO, 2013) recommends new methods and, in particular, metabolomics. The aim of this study is to determine total protein/EAA requirement in the plasma and urine of growing rats. METHODS: 36 weanling rats were fed with diets containing 3, 5, 8, 12, 15, and 20% protein for 3 weeks. During experimentation, urine was collected using metabolic cages, and blood from the portal vein and vena was taken at the end of the experiment. Metabolomics analyses were performed using LC-MS, and the data were analyzed with a multivariate analysis model, partial least Squares (PLS) regression, and independent component-discriminant analysis (ICDA). Each discriminant metabolite identified by PLS or ICDA was tested by one-way ANOVA to evaluate the effect of diet. RESULTS: PLS and ICDA allowed us to identify discriminating metabolites between different diet groups. Protein deficiency led to an increase in the AA catabolism enzyme systems inducing the production of breakdown metabolites in the plasma and urine. CONCLUSION: These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.


Assuntos
Aminoácidos Essenciais/sangue , Aminoácidos Essenciais/urina , Deficiências Nutricionais/diagnóstico , Proteínas na Dieta/sangue , Proteínas na Dieta/urina , Metabolômica/métodos , Aminoácidos Essenciais/deficiência , Análise de Variância , Ração Animal/análise , Animais , Biomarcadores/sangue , Biomarcadores/urina , Análise Discriminante , Modelos Animais de Doenças , Análise dos Mínimos Quadrados , Análise Multivariada , Avaliação Nutricional , Necessidades Nutricionais , Deficiência de Proteína/diagnóstico , Ratos
4.
Toxins (Basel) ; 13(6)2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071776

RESUMO

It is now recognized that additional exposure to mycotoxins may occur through inhalation of contaminated dust at a workplace. The aim of this study was to characterize the multi-mycotoxin exposure of French grain elevator workers using biomonitoring and airborne measurements. Eighteen workers participated in the study. Personal airborne dust samples were analyzed for their mycotoxin concentrations. Workers provided multiple urine samples including pre-shift, post-shift and first morning urine samples or 24 h urine samples. Mycotoxin urinary biomarkers (aflatoxin B1, aflatoxin M1, ochratoxin A, ochratoxin α, deoxynivalenol, zearalenone, α-zearalenol, ß-zearalenol, fumonisin B1, HT-2 toxin and T-2 toxin) were measured using a liquid chromatography-high-resolution mass spectrometry method. Grain elevator workers were highly exposed to organic airborne dust (median 4.92 mg.m-3). DON, ZEN and FB1 were frequent contaminants in 54, 76 and 72% of air samples, respectively. The mycotoxin biomarkers quantified were DON (98%), ZEN (99%), α-ZEL (52%), ß-ZEL (33%), OTA (76%), T-2 (4%) and HT-2 (4%). DON elimination profiles showed highest concentrations in samples collected after the end of the work shift and the urinary DON concentrations were significantly higher in post-shift than in pre-shift-samples (9.9 and 22.1 µg/L, respectively). ZEN and its metabolites concentrations did not vary according to the sampling time. However, the levels of α-/ß-ZEL were consistent with an additional occupational exposure. These data provide valuable information on grain worker exposure to mycotoxins. They also highlight the usefulness of multi-mycotoxin methods in assessing external and internal exposures, which shed light on the extent and pathways of exposure occurring in occupational settings.


Assuntos
Poluentes Ocupacionais do Ar/análise , Monitoramento Biológico/métodos , Micotoxinas/análise , Exposição Ocupacional , Adulto , Biomarcadores/urina , Fumonisinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ocratoxinas/análise , Zearalenona/análise
5.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073067

RESUMO

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.


Assuntos
Biomarcadores/urina , Peptídeos/análise , Urina/química , Humanos , Proteoma
6.
Sci Rep ; 11(1): 11134, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: covidwho-1246397

RESUMO

Risk factors associated with severity and mortality attributable to COVID-19 have been reported in different cohorts, highlighting the occurrence of acute kidney injury (AKI) in 25% of them. Among other, SARS-CoV-2 targets renal tubular cells and can cause acute renal damage. The aim of the present study was to evaluate the usefulness of urinary parameters in predicting intensive care unit (ICU) admission, mortality and development of AKI in hospitalized patients with COVID-19. Retrospective observational study, in a tertiary care hospital, between March 1st and April 19th, 2020. We recruited adult patients admitted consecutively and positive for SARS-CoV-2. Urinary and serum biomarkers were correlated with clinical outcomes (AKI, ICU admission, hospital discharge and in-hospital mortality) and evaluated using a logistic regression model and ROC curves. A total of 199 COVID-19 hospitalized patients were included. In AKI, the logistic regression model with a highest area under the curve (AUC) was reached by the combination of urine blood and previous chronic kidney disease, with an AUC of 0.676 (95%CI 0.512-0.840; p = 0.023); urine specific weight, sodium and albumin in serum, with an AUC of 0.837 (95% CI 0.766-0.909; p < 0.001) for ICU admission; and age, urine blood and lactate dehydrogenase levels in serum, with an AUC of 0.923 (95%CI 0.866-0.979; p < 0.001) for mortality prediction. For hospitalized patients with COVID-19, renal involvement and early alterations of urinary and serum parameters are useful as prognostic factors of AKI, the need for ICU admission and death.


Assuntos
Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/urina , COVID-19/mortalidade , COVID-19/urina , Injúria Renal Aguda/complicações , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Área Sob a Curva , Biomarcadores/urina , COVID-19/complicações , COVID-19/fisiopatologia , Cuidados Críticos , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Urina/química
7.
Aging (Albany NY) ; 13(10): 14322-14341, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34016789

RESUMO

The process of aging and metabolism is intimately intertwined; thus, developing biomarkers related to metabolism is critical for delaying aging. However, few studies have identified reliable markers that reflect aging trajectories based on machine learning. We generated metabolomic profiles from rat urine using ultra-performance liquid chromatography/mass spectrometry. This was dynamically collected at four stages of the rat's age (20, 50, 75, and 100 weeks) for both the training and test groups. Partial least squares-discriminant analysis score plots revealed a perfect separation trajectory in one direction with increasing age in the training and test groups. We further screened 25 aging-related biomarkers through the combination of four algorithms (VIP, time-series, LASSO, and SVM-RFE) in the training group. They were validated in the test group with an area under the curve of 1. Finally, six metabolites, known or novel aging-related markers, were identified, including epinephrine, glutarylcarnitine, L-kynurenine, taurine, 3-hydroxydodecanedioic acid, and N-acetylcitrulline. We also found that, except for N-acetylcitrulline (p < 0.05), the identified aging-related metabolites did not differ between tumor-free and tumor-bearing rats at 100 weeks (p > 0.05). Our findings reveal the metabolic trajectories of aging and provide novel biomarkers as potential therapeutic antiaging targets.


Assuntos
Envelhecimento/metabolismo , Envelhecimento/urina , Biomarcadores/urina , Aprendizado de Máquina , Metabolômica , Algoritmos , Animais , Peso Corporal , Comportamento Alimentar , Metaboloma , Neoplasias/urina , Ratos Wistar , Fatores de Tempo
8.
Sci Rep ; 11(1): 11134, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34045530

RESUMO

Risk factors associated with severity and mortality attributable to COVID-19 have been reported in different cohorts, highlighting the occurrence of acute kidney injury (AKI) in 25% of them. Among other, SARS-CoV-2 targets renal tubular cells and can cause acute renal damage. The aim of the present study was to evaluate the usefulness of urinary parameters in predicting intensive care unit (ICU) admission, mortality and development of AKI in hospitalized patients with COVID-19. Retrospective observational study, in a tertiary care hospital, between March 1st and April 19th, 2020. We recruited adult patients admitted consecutively and positive for SARS-CoV-2. Urinary and serum biomarkers were correlated with clinical outcomes (AKI, ICU admission, hospital discharge and in-hospital mortality) and evaluated using a logistic regression model and ROC curves. A total of 199 COVID-19 hospitalized patients were included. In AKI, the logistic regression model with a highest area under the curve (AUC) was reached by the combination of urine blood and previous chronic kidney disease, with an AUC of 0.676 (95%CI 0.512-0.840; p = 0.023); urine specific weight, sodium and albumin in serum, with an AUC of 0.837 (95% CI 0.766-0.909; p < 0.001) for ICU admission; and age, urine blood and lactate dehydrogenase levels in serum, with an AUC of 0.923 (95%CI 0.866-0.979; p < 0.001) for mortality prediction. For hospitalized patients with COVID-19, renal involvement and early alterations of urinary and serum parameters are useful as prognostic factors of AKI, the need for ICU admission and death.


Assuntos
Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/urina , COVID-19/mortalidade , COVID-19/urina , Injúria Renal Aguda/complicações , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Área Sob a Curva , Biomarcadores/urina , COVID-19/complicações , COVID-19/fisiopatologia , Cuidados Críticos , Feminino , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Urina/química
9.
Biomed Res Int ; 2021: 6637235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997033

RESUMO

Objectives: Systemic vasculitis includes a group of disorders characterized by inflammation of the vessel wall, involving multiple systems, and can cause malignant hypertension. CD163 is a specific marker of anti-inflammatory macrophages. This study is aimed at evaluating the CD163 levels in relation to systemic vasculitis and renal involvements. Methods: Urinary CD163 levels were retrospectively measured by enzyme-linked immunosorbent assay (ELISA) in 51 patients with systemic vasculitis, 42 essential hypertensions, and 36 healthy volunteers. The associations between urinary CD163 levels and clinical indicators were analyzed. Results: Urinary CD163 levels were significantly higher in patients with systemic vasculitis [68.20 (38.25~158.78) (pg/ml)] compared to essential hypertension [43.86 (23.30-60.71) (pg/ml)] (p = 0.003) and the healthy volunteers [30.76 (9.30-54.16) (pg/ml)] (p < 0.001). Furthermore, systemic vasculitis patients with renal involvement had significantly higher urinary CD163 levels relative to patients without renal involvement [86.95 (47.61 and 192.38) pg/ml] vs. [41.99 (17.70 and 71.95) pg/ml, p = 0.005]. After control factors age, sex, and BMI, urinary CD163 levels in systemic vasculitis patients were positively correlated with serum creatinine, blood urea nitrogen, and ß-2 microglobulin (r = 0.45, 0.48, and 0.46; p = 0.001, 0.001, and 0.002, respectively). In addition, we found the level of urinary CD163 in granulomatous vasculitis (including TA, GPA, and EGPA) was significantly higher than that in necrotizing vasculitis (including PAN) [86.95 (41.99 and 184.82) pg/ml] vs. [45.73 (21.43 and 74.43) pg/ml, p = 0.016]. Conclusion: Urinary CD163 levels were significantly higher in patients with systemic vasculitis, especially in patients with renal involvement. Thus, urinary CD163 has the potential to be a biomarker for systemic vasculitis with renal involvement.


Assuntos
Antígenos CD/urina , Antígenos de Diferenciação Mielomonocítica/urina , Nefropatias/urina , Vasculite Sistêmica/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular , Estudos Retrospectivos , Vasculite Sistêmica/complicações , Adulto Jovem
10.
J Vis Exp ; (170)2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33970146

RESUMO

Extracellular vesicles, EVs, are a heterogeneous complex of lipidic membranes, secreted by any cell type, in any fluid such as urine. EVs can be of different sizes ranging from 40-100 nm in diameter such as in exosomes to 100-1000 nm in microvesicles. They can also contain different molecules that can be used as biomarkers for the prognosis and diagnosis of many diseases. Many techniques have been developed to characterize these vesicles. One of these is flow cytometry. However, there are no existing reports to show how to quantify the concentration of EVs and differentiate them by size, along with biomarker detection. This work aims to describe a procedure for the isolation, quantification, and phenotypification of urinary extracellular vesicles, uEVs, using a conventional cytometer for the analysis without any modification to its configuration. The method's limitations include staining a maximum of four different biomarkers per sample. The method is also limited by the amount of EVs available in the sample. Despite these limitations, with this protocol and its subsequent analysis, we can obtain more information on the enrichment of EVs markers and the abundance of these vesicles present in urine samples, in diseases involving kidney and brain damage.


Assuntos
Biomarcadores/urina , Vesículas Extracelulares/metabolismo , Citometria de Fluxo/métodos , Tamanho Celular , Humanos , Fenótipo
11.
Ann Hematol ; 100(6): 1401-1409, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33796899

RESUMO

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.


Assuntos
Injúria Renal Aguda/sangue , Anemia Falciforme/sangue , Lipocalina-2/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lipocalina-2/urina , Masculino , Curva ROC
12.
Toxins (Basel) ; 13(4)2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917988

RESUMO

Mycotoxins are naturally occurring food toxins worldwide that can cause serious health effects. The measurement of mycotoxin biomarkers in biological fluids is needed to assess individuals' exposure. The aim of this study was to investigate the incidence of mycotoxins in the Qatari population. Serum samples from 412 adults and urinary samples from 559 adults were analyzed for the presence of mycotoxin biomarkers. Multimycotoxin approaches have been applied, using liquid chromatography mass spectrometry methods. Samples were further analyzed for the oxidative stress markers and compared with regard to the incidence of mycotoxins. The presence of mycotoxins was identified in 37% of serum samples and in less than 20% of urine samples. It was found that 88% of positive of the samples were positive for only one mycotoxin, while 12% of positive samples had two or more mycotoxins. Trichothecenes and zearalenone metabolites were most commonly detected mycotoxins, followed by aflatoxins, roquefortine C and mycophenolic acid. The presence of mycotoxins was found to positively correlate with oxidative stress markers. The obtained results illustrate the importance of mycotoxin biomonitoring studies in humans and the need to elucidate the underlying mechanisms of mycotoxin-induced toxicity.


Assuntos
Monitoramento Biológico , Contaminação de Alimentos , Micotoxinas/sangue , Micotoxinas/urina , Estresse Oxidativo , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Carga Corporal (Radioterapia) , Cromatografia Líquida de Alta Pressão , Dano ao DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Catar , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
13.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801801

RESUMO

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.


Assuntos
Injúria Renal Aguda/metabolismo , Biomarcadores/metabolismo , Exossomos/metabolismo , Inflamação/metabolismo , Proteômica/métodos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Adulto , Biomarcadores/urina , Cromatografia Líquida/métodos , Creatinina/urina , Humanos , Inflamação/urina , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Vancomicina/efeitos adversos , Adulto Jovem
14.
Nutrients ; 13(4)2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916877

RESUMO

The western dietary pattern is known for its frequent meals rich in saturated fat and protein, resulting in a postprandial state for a large part of the day. Therefore, our aim was to investigate the postprandial glucose and lipid metabolism in response to high (HP) or normal (NP) protein, high-fat hypercaloric diet and to identify early biomarkers of protein intake and hepatic lipid accumulation. In a crossover design, 17 healthy subjects were randomly assigned to consume a HP or NP hypercaloric diet for two weeks. In parallel, a control group (CD; n = 10) consumed a weight-maintaining control diet. Biomarkers of postprandial lipid and glucose metabolism were measured in 24 h urine and in plasma before and following a meal challenge. The metabolic profile of urine but not plasma, showed increased excretion of 13C, carnitine and short chain acyl-carnitines after adaptation to the HP diet. Urinary excretion of decatrienoylcarnitine and octenoylcarnitine increased after adaptation to the NP diet. Our results suggest that the higher excretion of short-chain urinary acyl-carnitines could facilitate the elimination of excess fat of the HP diet and thereby reduce hepatic fat accumulation previously reported, whereas the higher excretion medium-chains acyl-carnitine could be early biomarkers of hepatic lipid accumulation.


Assuntos
Carnitina/análogos & derivados , Dieta Hiperlipídica/efeitos adversos , Dieta Rica em Proteínas/efeitos adversos , Dieta Ocidental/efeitos adversos , Síndrome Metabólica/diagnóstico , Adulto , Biomarcadores/urina , Carnitina/metabolismo , Carnitina/urina , Estudos Cross-Over , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Proteínas na Dieta/metabolismo , Ingestão de Energia/fisiologia , Feminino , Glucose/metabolismo , Voluntários Saudáveis , Humanos , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/urina , Período Pós-Prandial/fisiologia , Eliminação Renal/fisiologia , Adulto Jovem
15.
Int J Mol Sci ; 22(8)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920653

RESUMO

Mitochondria are well-known to function as the primary sites of ATP synthesis in most mammalian cells, including the renal proximal tubule. Other functions have also been associated with different mitochondrial activities, including the regulation of redox status and the initiation of mitophagy and apoptosis. Mechanisms for the membrane transport of glutathione (GSH) and various GSH-derived metabolites across the mitochondrial inner membrane of renal proximal tubular cells are critical determinants of these functions and may serve as pharmacological targets for potential therapeutic approaches. Specific interactions of reactive intermediates, derived from drug metabolism, with molecular components in mitochondria have been identified as early steps in diverse forms of chemically-induced nephrotoxicity. Applying this key observation, we developed a novel hypothesis regarding the identification of early, sensitive, and specific biomarkers of exposure to nephrotoxicants. The underlying concept is that upon exposure to a diverse array of environmental contaminants, as well as therapeutic drugs whose efficacy is limited by nephrotoxicity, renal mitochondria will release both high- and low-molecular-weight components into the urine or the extracellular medium in an in vitro model. The detection of these components may then serve as indicators of exposure before irreversible renal injury has occurred.


Assuntos
Nefropatias/induzido quimicamente , Mitocôndrias/metabolismo , Animais , Biomarcadores/urina , Poluentes Ambientais/toxicidade , Humanos , Nefropatias/metabolismo , Nefropatias/urina , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Mitocôndrias/efeitos dos fármacos , Oxidantes/toxicidade
16.
Toxicol Lett ; 345: 61-66, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33872748

RESUMO

Acute kidney injury (AKI) is a frequent and potentially fatal complication of snakebites. In the setting of snakebites, endothelial biomarkers may be used to predict disease severity and can play a major role in AKI pathophysiology. The aim of this study was to investigate the potential role of endothelial biomarkers in predicting AKI in Bothrops envenoming. Therefore, blood and urine samples were collected from 26 patients admitted to the emergency department after Bothrops envenoming at 3 different post-bite points in time: on admission (up to 8 h post-bite), 12-16 h, and 24-28 h post-bite, to investigate the time course of endothelial biomarkers in AKI following Bothrops snakebites. The diagnostic performance of injury biomarkers in Bothrops envenomation was evaluated. AKI was diagnosed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. There was an association between endothelial injury and increased risk for AKI in bothropic envenoming. Angiopoietin- 1 (Ang-1) and Vascular cell adhesion protein-1 (VCAM-1) were useful biomarkers to predict mild AKI [AUC-ROC: Ang-1 0.82, VCAM-1 0.76] within the interval of 8-16 h post Bothrops snakebites. The use of endothelial biomarkers VCAM-1 e Ang-1 within 12-16 h post-bite may be useful in the early stage of mild AKI related to Bothrops envenoming and might have an effect on the early intervention for renal protection in less severe Bothrops-related AKI.


Assuntos
Injúria Renal Aguda/etiologia , Angiopoietina-1/sangue , Bothrops , Venenos de Crotalídeos/metabolismo , Células Endoteliais/metabolismo , Rim/metabolismo , Mordeduras de Serpentes/complicações , Molécula 1 de Adesão de Célula Vascular/sangue , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Adulto , Animais , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Mordeduras de Serpentes/metabolismo , Fatores de Tempo
17.
Am J Clin Nutr ; 113(5): 1232-1240, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33826700

RESUMO

BACKGROUND: Early applications of metabolomics in nutrition and health research identified associations between dietary patterns and metabolomic profiles. Twin studies show that diet-related phenotypes and diet-associated metabolites are influenced by genes. However, studies have not examined whether diet-metabolite associations are explained by genetic or environmental factors and whether these associations are reproducible over multiple time points. OBJECTIVE: This research aims to examine the genetic and environmental factors influencing covariation in diet-metabolite associations that are reproducible over time in healthy twins. METHODS: The UCD Twin Study is a semi-longitudinal classic twin study that collected repeated dietary, anthropometric, and urinary data over 2 months. Correlation analysis identified associations between diet quality measured using the Healthy Eating Index (HEI) and urinary metabolomic profiles at 3 time points. Diet-associated metabolites were examined using linear regression to identify those significantly influenced by familial factors between twins and those significantly influenced by unique factors. Cholesky decomposition modeling quantified the genetic and environmental path coefficients through associated dietary components onto the metabolites. RESULTS: The HEI was associated with 14 urinary metabolites across 3 metabolomic profiles (r: ±0.15-0.49). For 8 diet-metabolite associations, genetic or shared environmental factors influencing HEI component scores significantly influenced variation in metabolites (ß: 0.40-0.52). A significant relation was observed between dietary intakes of whole grain and acetoacetate (ß: -0.50, P < 0.001) and ß-hydroxybutyrate (ß: -0.46, P < 0.001), as well as intakes of saturated fat and acetoacetate (ß: 0.47, P < 0.001) and ß-hydroxybutyrate (ß: 0.52, P < 0.001). For these diet-metabolite associations a common shared environmental factor explained 66-69% of variance in the metabolites. CONCLUSIONS: This study shows that diet-metabolite associations are reproducible in 3 urinary metabolomic profiles. Components of the HEI covary with metabolites, and covariation is largely due to the shared environment.


Assuntos
Dieta Saudável , Comportamento Alimentar , Metabolômica , Gêmeos , Adolescente , Adulto , Biomarcadores/urina , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Urinálise , Adulto Jovem
18.
Molecules ; 26(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807567

RESUMO

Catecholamines are physiological regulators of carbohydrate and lipid metabolism during stress, but their chronic influence on metabolic changes in obese patients is still not clarified. The present study aimed to establish the associations between the catecholamine metabolites and metabolic syndrome (MS) components in obese women as well as to reveal the possible hidden subgroups of patients through hierarchical cluster analysis and principal component analysis. The 24-h urine excretion of metanephrine and normetanephrine was investigated in 150 obese women (54 non diabetic without MS, 70 non-diabetic with MS and 26 with type 2 diabetes). The interrelations between carbohydrate disturbances, metabolic syndrome components and stress response hormones were studied. Exploratory data analysis was used to determine different patterns of similarities among the patients. Normetanephrine concentrations were significantly increased in postmenopausal patients and in women with morbid obesity, type 2 diabetes, and hypertension but not with prediabetes. Both metanephrine and normetanephrine levels were positively associated with glucose concentrations one hour after glucose load irrespectively of the insulin levels. The exploratory data analysis showed different risk subgroups among the investigated obese women. The development of predictive tools that include not only traditional metabolic risk factors, but also markers of stress response systems might help for specific risk estimation in obesity patients.


Assuntos
Metanefrina/urina , Análise Multivariada , Normetanefrina/urina , Obesidade/urina , Adolescente , Adulto , Idoso , Biomarcadores/urina , Análise por Conglomerados , Diabetes Mellitus Tipo 2/urina , Feminino , Humanos , Síndrome Metabólica/urina , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Circunferência da Cintura
19.
Molecules ; 26(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804943

RESUMO

Volatile organic compounds (VOCs) exiting in urine are potential biomarkers of chronic kidney diseases. Headspace solid phase microextraction (HS-SPME) was applied for extraction VOCs over the urine samples. Volatile metabolites were separated and identified by means of two-dimensional gas chromatography and time of flight mass spectrometry (GC × GC TOF MS). Patients with glomerular diseases (n = 27) and healthy controls (n = 20) were recruited in the study. Different VOCs profiles were obtained from patients and control. Developed methodology offers the opportunity to examine the metabolic profile associated with glomerulopathy. Four compounds found in elevated amounts in the patients group, i.e., methyl hexadecanoate; 9-hexadecen-1-ol; 6,10-dimethyl-5,9-undecadien-2-one and 2-pentanone were proposed as markers of glomerular diseases.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Insuficiência Renal Crônica/urina , Compostos Orgânicos Voláteis/urina , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Molecules ; 26(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806905

RESUMO

In this work, previously synthesized and characterized core-shell silica nanoparticles (FCSNP) functionalized with immobilized molecular bait, Cibacron blue, and a porous polymeric bis-acrylamide shell were incubated with pooled urine samples from adult women or men with normal weight, overweight or obesity for the isolation of potential biomarkers. A total of 30 individuals (15 woman and 15 men) were included. FCSNP allowed the capture of a variety of low molecular weight (LMW) proteins as evidenced by mass spectrometry (MS) and the exclusion of high molecular weight (HMW) proteins (>34 kDa) as demonstrated by SDS-PAGE and 2D SDS-PAGE. A total of 36 proteins were successfully identified by MS and homology database searching against the Homo sapiens subset of the Swiss-Prot database. Identified proteins were grouped into different clusters according to their abundance patterns. Four proteins were found only in women and five only in men, whereas 27 proteins were in urine from both genders with different abundance patterns. Based on these results, this new approach represents an alternative tool for isolation and identification of urinary biomarkers.


Assuntos
Obesidade/urina , Proteinúria/urina , Proteômica , Adulto , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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