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1.
J Clin Lab Anal ; 35(5): e23748, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33709460

RESUMO

BACKGROUND: Urinary N-acetyl-beta-D-glucosaminidase (NAG) plays an important role in the early diagnosis and progression of diseases related to renal tubular injury. We detected the urinary NAG concentration, assessed the preliminary statistics of its distribution, and established reference intervals for healthy adults in China using the rate method. METHODS: A total of 1,095 reference individuals (aged 20 to 79 years) met the requirements for inclusion in this study. Urinary NAG concentrations were detected using an AU5800 automatic biochemical analyzer with its matched reagents. The Kolmogorov-Smirnov test was used to analyze the normality of the data. According to the guidelines of C28-A3 and WS/T 402-2012, the reference intervals of urinary NAG were established using the nonparametric percentile method (unilateral 95th percentile). RESULTS: The urinary NAG data showed a non-normal distribution. The distribution of urinary NAG was significantly different by sex and age. Therefore, the reference intervals of urinary NAG were established using the rate method: males (aged 20-59 years) <19.4 U/L (90% CI: 18.0-20.3 U/L); males (aged 60-79 years) <22.3 U/L (90% CI: 20.2-22.6 U/L); females (aged 20-59 years) <15.7 U/L (90% CI: 15.2-16.5 U/L); and females (aged 60-79 years) <21.4 U/L (90% CI: 20.3-22.3 U/L). CONCLUSIONS: We established preliminary reference intervals of urinary NAG for healthy adults in China to provide guidance for health screening, auxiliary diagnosis, and treatment monitoring of renal tubule-related diseases.


Assuntos
Acetilglucosaminidase/urina , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
2.
Diab Vasc Dis Res ; 18(1): 1479164121990533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33535822

RESUMO

OBJECTIVE: Interaction of advanced glycation end products (AGEs) with the receptor RAGE plays a role in diabetic nephropathy. However, effects of RAGE-aptamer on tubular damage remain unknown. We examined whether RAGE-aptamer inhibited tubular damage in KKAy/Ta mice, obese type 2 diabetic mice with insulin resistance. MATERIALS AND METHODS: Male 8-week-old KKAy/Ta mice received continuous intraperitoneal infusion of either control-aptamer or RAGE-aptamer for 8 weeks. Blood biochemistry and blood pressure, and urinary N-acetyl-ß-D-glucosaminidase (NAG) activity and albumin excretion levels were monitored. Kidney and adipose tissue samples were obtained for immunohistochemical analyses. RESULTS: Although RAGE-aptamer did not affect blood glucose, blood pressure, body weight, or serum creatinine values, it significantly inhibited the increase in urinary NAG activity and HOMA-IR in diabetic mice at 12 and 16 and at 16 weeks old, respectively. Furthermore, compared with control-aptamer-treated mice, renal carboxymethyllysine, RAGE, and NADPH oxidase-driven superoxide generation were significantly decreased in RAGE-aptamer-treated mice at 12 weeks old with subsequent amelioration of histological alterations in glomerular and interstitial area, while adipose tissue adiponectin expression was increased. CONCLUSION: Our present results suggest that RAGE-aptamer could inhibit tubular injury in obese type 2 diabetic mice partly by suppressing the AGE-RAGE-oxidative stress axis and improving insulin resistance.


Assuntos
Aptâmeros de Nucleotídeos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Produtos Finais de Glicação Avançada/metabolismo , Resistência à Insulina , Túbulos Renais/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Acetilglucosaminidase/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Insulina/sangue , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Camundongos , Obesidade/complicações , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais
3.
Int J Mol Sci ; 22(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578883

RESUMO

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-ß-D-glucosaminidase concentrations ([Cd]u and [NAG]u) to the urine creatinine concentration ([cr]u). In theory, the sources of these errors are nullified by normalization of excretion rates (ECd and ENAG) to creatinine clearance (Ccr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, Ex/Ecr and Ex/Ccr were calculated as [x]u/[cr]u and [x]u[cr]p/[cr]u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m2. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(ECd/Ccr) and log(ENAG/Ccr) than for log(ECd/Ecr) and log(ENAG/Ecr). Doubling of ECd/Ccr and ENAG/Ccr increased POR by 132% and 168%; doubling of ECd/Ecr and ENAG/Ecr increased POR by 64% and 54%. As log(ECd/Ccr) rose, associations of eGFR with log(ECd/Ccr) and log(ENAG/Ccr) became stronger, while associations of eGFR with log(ECd/Ecr) and log(ENAG/Ecr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R2 was consistently higher with normalization to Ccr. Our tabular and graphic analyses uniformly indicate that normalization to Ccr clarified relationships of ECd and ENAG to eGFR.


Assuntos
Cádmio/efeitos adversos , Creatinina/urina , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/urina , Acetilglucosaminidase/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cádmio/urina , Exposição Ambiental/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Túbulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Adulto Jovem
4.
Ecotoxicol Environ Saf ; 203: 111044, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888613

RESUMO

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.


Assuntos
Poluentes Atmosféricos/toxicidade , Angiotensina I/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Material Particulado/toxicidade , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Acetilglucosaminidase/urina , Angiotensina I/sangue , Enzima de Conversão de Angiotensina 2 , Animais , Biomarcadores/sangue , Biomarcadores/urina , Hipertensão/urina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , beta-Galactosidase/urina
5.
Vet Anaesth Analg ; 47(5): 631-636, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32792267

RESUMO

OBJECTIVE: To compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-ß-D-glucosaminidase (NAG) activity, of cats after dental surgery. STUDY DESIGN: Randomized, blinded, controlled trial. ANIMALS: A total of 24 mixed breed cats. METHODS: Cats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg-1); carprofen (4 mg kg-1); or saline (2 mL). Acepromazine (0.04 mg kg-1) and buprenorphine (0.02 mg kg-1) were administered intramuscularly as preanaesthetic medication. Test drugs were injected subcutaneously at the time of preanaesthetic medication. Anaesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. Mean arterial blood pressure (MAP), respiratory rate (fR), heart rate (HR) and haemoglobin oxygen saturation values (SpO2) were recorded. All cats underwent ultrasonic dental scaling with polishing. Teeth extraction involved mucosal flap creation, removal of alveolar bone and flap closure. Plasma iohexol clearance (ICL), a measure of GFR, was estimated before and 24 hours after anaesthesia induction in all cats. Urinary NAG index was estimated in saline and meloxicam groups at the same time points as GFR. Between-group and -time point differences in GFR and NAG index were compared using mixed model analyses. Data are presented as mean ± standard deviation (p < 0.05). RESULTS: There was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute-1) between groups or between time points. Urinary NAG index (range: from 1.0 ± 0.19 to 1.36 ± 0.29 Units gram-1) was not significantly different between meloxicam and saline groups. MAP, HR, fR and SpO2 did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.


Assuntos
Acetilglucosaminidase/urina , Carbazóis/farmacologia , Doenças do Gato/cirurgia , Taxa de Filtração Glomerular/veterinária , Meloxicam/farmacologia , Doenças Dentárias/veterinária , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Carbazóis/administração & dosagem , Carbazóis/efeitos adversos , Gatos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Masculino , Meloxicam/administração & dosagem , Meloxicam/efeitos adversos , Doenças Dentárias/cirurgia
6.
Ecotoxicol Environ Saf ; 200: 110741, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497990

RESUMO

Environmental exposure to melamine has been associated with early renal injury in urolithiasis patients even when urinary concentrations of melamine are low. The aim of this study was to derive a benchmark dose (BMD) for melamine for urolithiasis patients. To do this, one-spot urine sample from 309 participants was obtained to measure urinary melamine and N-acetyl ß-D-glucosaminidase (NAG), an early renal damage biomarker. The participants were then classified into four exposure groups based on the outcomes of melamine tableware usage questionnaire. A beta distribution of urinary excretion fraction for each group was assumed to estimate their average daily intakes (AvDIs) of melamine. The BMD and the corresponding one-sided 95% lower bound (BMDL) was then derived based on Bayesian model averaging of alternative regression models between the participants' NAG levels and their estimated AvDIs, adjusting for age, gender, and other covariates. Bayesian Markov chain Monte Carlo simulations were used for all the estimates. With a benchmark response of 0.10, the simulated BMDL of 4.89 µg/kg-bw/day for melamine exposure threshold was much lower than the WHO's current recommended tolerable daily intake of 200 µg/kg_bw/day and the US FDA's 63 µg/kg_bw/day. The current regulation level of melamine might not safeguard urolithiasis patients from further deterioration of renal function.


Assuntos
Cálcio , Rim/efeitos dos fármacos , Triazinas/toxicidade , Triazinas/urina , Urolitíase/urina , Acetilglucosaminidase/urina , Adulto , Idoso , Teorema de Bayes , Biomarcadores/urina , Exposição Ambiental , Feminino , Humanos , Rim/fisiopatologia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Probabilidade , Urolitíase/fisiopatologia
7.
Sci Rep ; 10(1): 9603, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32541800

RESUMO

Metallothionein (MT) is a protein with function of heavy metal detoxification. However, studies about how single nucleotide polymorphisms (SNPs) of MT genes influence lead nephropathy are relatively scarce. Therefore, our aim is to investigate the association between blood lead levels and renal biomarkers and to study whether this association is influenced by the combination of MT1A and MT2A SNPs. Blood lead, urinary uric acid (UA), and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were analyzed from 485 participants. Genotyping were performed on MT1A SNPs (rs11640851 and rs8052394) and MT2A SNPs (rs10636 and rs28366003). The combined MT1A 2A SNPs were divided into 16 groups. Among renal biomarkers, urinary UA was negatively significant associated with the time-weighted index of cumulative blood lead (TWICL), while urinary NAG was positively significant with TWICL. Furthermore, the association between urinary UA and TWICL was significantly modified by group 6 of combined SNPs (MT1A 2 A SNPs combination were AAAGGGAA, ACAGGGAA, and ACGGGGAA). In conclusion, the negative association of urinary UA and TWICL is modified by group 6, which means participants of group 6 are more susceptible to lead nephrotoxicity.


Assuntos
Rim/efeitos dos fármacos , Intoxicação por Chumbo/genética , Chumbo/sangue , Metalotioneína/genética , Polimorfismo de Nucleotídeo Único/genética , Acetilglucosaminidase/urina , Adulto , Biomarcadores/urina , Feminino , Humanos , Masculino , Metalotioneína/metabolismo , Pessoa de Meia-Idade , Ácido Úrico/urina
8.
Interv Cardiol Clin ; 9(3): 335-344, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32471674

RESUMO

Contrast-induced acute kidney injury (CI-AKI) is a common complication after intravascular injection of iodinated contrast media, and it is associated with a prolonged in-hospital stay and unfavorable outcome. CI-AKI occurs in 5% to 20% among hospitalized patients. Its diagnosis relies on the increase in serum creatinine levels, which is a late biomarker of kidney injury. Novel and early serum and urinary biomarkers have been identified to detect kidney damage before the expected serum creatinine increase.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Meios de Contraste/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Acetilglucosaminidase/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Proteínas Adaptadoras de Transdução de Sinal/urina , Albuminúria/diagnóstico , Meios de Contraste/administração & dosagem , Creatinina/sangue , Cistatina C/sangue , Proteínas de Ligação a Ácido Graxo/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Humanos , Interleucina-18/urina , Lipocalina-2/urina , Masculino , Midkina/sangue , Proteínas de Ligação ao Retinol/urina , Microglobulina beta-2/sangue , Microglobulina beta-2/urina
9.
Environ Toxicol Pharmacol ; 79: 103381, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32413495

RESUMO

To investigate heavy metal exposure in an industrial zone vs. a living quarter in Shanghai and explore the relationship between the heavy metal source and urine cadmium (Cd) and early kidney damage. Blood lead and urine Cd, manganese (Mn), mercury (Hg), arsenic (As) and EKD indexes were compared between residents in Exposure group (n = 168) and Control group (n = 168). It was found that PM2.5 level in Exposure group was significantly higher than that in Control group, and serum Cys-C and urine Cd, NAG, mAlb, KIM-1 and Cd-MT levels in Exposure group were also significantly higher than those in Control group, suggesting that differences in urine Cd and heavy metal levels between the residents of the two groups may be due to different PM2.5 concentrations in the environments of the two areas. Cd accumulation within the human body can induce kidney damage, probably through its potential hazard to the proximal tubular epithelial cells.


Assuntos
Cádmio/análise , Exposição Ambiental/análise , Poluentes Ambientais/análise , Nefropatias/epidemiologia , Acetilglucosaminidase/urina , Adolescente , Adulto , Albuminúria , China/epidemiologia , Cistatina C/sangue , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Habitação , Humanos , Indústrias , Rim , Nefropatias/sangue , Nefropatias/urina , Metalotioneína/urina , Pessoa de Meia-Idade , Proteínas de Ligação ao Retinol/urina , Adulto Jovem
10.
Anal Chem ; 92(8): 6166-6172, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32241110

RESUMO

Drug-induced kidney injury (DIKI) is a significant contributor of both acute and chronic kidney injury and remains a major concern in drug development and clinical care. However, current clinical diagnostic methods often fail to accurately and timely detect nephrotoxicity. This study reports the development of activatable molecular urinary reporters (MURs) that are able to specifically detect urinary biomarkers including γ-glutamyl transferase (GGT), alanine aminopeptidase (AAP), and N-acetyl-ß-d-glucosaminidase (NAG). By virtue of their discrete absorption and emission properties, the mixture of MURs can serve as a cocktail sensor for multiplex optical urinalysis in the mouse models of drug-induced acute kidney injury (AKI) and chronic kidney disease (CKD). The MURs cocktail not only detects nephrotoxicity earlier than the tested clinical diagnostic methods in drug-induced AKI and CKD mice models, but also possesses a higher diagnostic accuracy. Therefore, MURs hold great promise for detection of kidney function in both preclinical drug screening and clinical settings.


Assuntos
Acetilglucosaminidase/urina , Injúria Renal Aguda/urina , Antígenos CD13/urina , Insuficiência Renal Crônica/urina , gama-Glutamiltransferase/urina , Acetilglucosaminidase/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Animais , Biomarcadores/urina , Antígenos CD13/metabolismo , Células Cultivadas , Cisplatino , Modelos Animais de Doenças , Doxorrubicina , Humanos , Camundongos , Imagem Óptica , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/diagnóstico , gama-Glutamiltransferase/metabolismo
11.
Ecotoxicol Environ Saf ; 191: 110251, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32006870

RESUMO

Cadmium exposure is associated with renal dysfunction. However, the outcome of renal function in subjects who have had a reduction in cadmium exposure for years has not been completely clarified, particularly for individuals with normal baseline renal function. In this study, we used a nomogram model to predict renal dysfunction after a reduction in cadmium exposure in subjects with normal baseline renal function. In 1998, a survey was performed in 790 subjects living in control and cadmium-polluted areas. A total of 497 subjects was followed up in 2006. 404 subjects with normal baseline urinary ß2-microglobulin (UBMG), 373 subjects with normal baseline urinary N-acetyl-ß-d-glucosaminidase (UNAG) and 407 subjects with normal baseline urinary albumin (UALB) were included in this analysis. Cadmium in the blood (BCd) and urine (UCd) was detected using graphite-furnace atomic absorption spectrometry. A logistic regression model was used to identify potential predicting factors of renal function at follow-up. Nomograms were developed based on those predictive factors. Bootstrap self-sampling, calibration curves and receiver operating characteristic (ROC) curves were performed to quantify our modeling strategy. Adjusted and unadjusted logistic regression models both showed that age, BCd and UBMG or UNAG at baseline were independent risk factors for renal tubular dysfunction. Baseline age, sex, BCd and UNAG or UBMG or UALB were used to construct the nomogam. The internal validation showed that the C-index was 0.70-0.74 for predicting renal dysfunction. The area under the curve of the nomogram was 0.70-0.74. Decision curve analysis verified the predictive value of the nomogram. A nomogram may be a useful risk assessment tool for predicting the progress of renal function in a cadmium-exposed population with normal baseline kidney function.


Assuntos
Cádmio/sangue , Exposição Ambiental/análise , Poluentes Ambientais/sangue , Nefropatias/epidemiologia , Nomogramas , Acetilglucosaminidase/urina , Adulto , China , Exposição Ambiental/efeitos adversos , Feminino , Seguimentos , Humanos , Nefropatias/induzido quimicamente , Nefropatias/urina , Testes de Função Renal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Microglobulina beta-2/urina
12.
Anal Chim Acta ; 1101: 129-134, 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32029103

RESUMO

Carbon dots (CDs) were synthesized from p-aminophenol and ethylenediamine via one-step under mild condition and used as a sensitive fluorescent nanoprobe for the activity determination of N-acetyl-ß-d-glucosaminidase (NAG). In this assay, p-nitrophenol was in situ produced from p-nitrophenyl-ß-D-N-acetyl-glucosaminide, which was exclusively hydrolyzed by NAG. The UV absorption peak of p-nitrophenol (maximum at 400 nm) overlapped the excitation peak of CDs with maximum wavelength at 415 nm, which caused the fluorescence decline of CDs based on inner filter effect. The activity of NAG was determined by the fluorescence changes. The assay is highly sensitive to NAG with a low detection limit of 0.75 U L-1 (K = 3) and showed a good linear relationship in the range from 1 to 45 U L-1. This CDs nanoprobe was successfully applied for the determination of NAG activity in human serum and urine samples.


Assuntos
Acetilglucosaminidase/sangue , Acetilglucosaminidase/urina , Corantes Fluorescentes/química , Pontos Quânticos/química , Carbono/química , Ensaios Enzimáticos , Humanos , Limite de Detecção , Espectrometria de Fluorescência
13.
Kidney Blood Press Res ; 45(1): 142-156, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31927548

RESUMO

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent and associated with adverse outcomes. Unfortunately, the early diagnosis of AKI remains a challenge. Combining functional and tubular damage biomarkers may provide better precision for AKI detection. However, the diagnostic accuracy of this combination for AKI after neurosurgery is unclear. Serum cystatin C (sCysC) and urinary albumin/creatinine ratio (uACR) are considered functional biomarkers, while urinary N-acetyl-ß-D-glucosaminidase (uNAG) represents tubular damage. We aimed to assess the performances of these clinical available biomarkers and their combinations for AKI prediction after resection of intracranial space-occupying lesions. METHODS: A prospective study was conducted, enrolling adults undergoing resection of intracranial space-occupying lesions and admitted to the neurosurgical intensive care unit. The discriminative abilities of postoperative sCysC, uNAG, uACR, and their combinations in predicting AKI were compared using the area under the receiver operating characteristic curve (AUC-ROC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). RESULTS: Of 605 enrolled patients, AKI occurred in 67 patients. The cutoff values of sCysC, uNAG, and uACR to predict postoperative AKI were 0.72 mg/L, 19.98 U/g creatinine, and 44.21 mg/g creatinine, respectively. For predicting AKI, the composite of sCysC and uNAG (AUC-ROC = 0.785) outperformed either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). Adding this panel to the predictive model improved the AUC-ROC to 0.808. Moreover, this combination significantly improved risk reclassification over the clinical model alone, with cNRI (0.633) and IDI (0.076). Superior performance of this panel was further confirmed with bootstrap internal validation. CONCLUSIONS: Combination of functional and tubular damage biomarkers improves the predictive accuracy for AKI after resection of intracranial space-occupying lesions.


Assuntos
Acetilglucosaminidase/metabolismo , Injúria Renal Aguda/diagnóstico , Neoplasias Encefálicas/complicações , Encéfalo/patologia , Cistatina C/metabolismo , Acetilglucosaminidase/urina , Injúria Renal Aguda/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Eur Heart J Acute Cardiovasc Care ; 9(5): 429-436, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31990204

RESUMO

BACKGROUND: The prognostic significance of urinary N-acetyl-ß-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary N-acetyl-ß-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients. METHODS: We studied 708 consecutive acute heart failure patients who had accessible N-acetyl-ß-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission N-acetyl-ß-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge. RESULTS: During a median follow-up period of 763 (interquartile range 431-1028) days, higher urinary N-acetyl-ß-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary N-acetyl-ß-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary N-acetyl-ß-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04-1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate. CONCLUSIONS: Higher urinary N-acetyl-ß-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary N-acetyl-ß-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.


Assuntos
Acetilglucosaminidase/urina , Insuficiência Cardíaca/urina , Admissão do Paciente , Sistema de Registros , Doença Aguda , Idoso , Biomarcadores/urina , Progressão da Doença , Feminino , Seguimentos , Insuficiência Cardíaca/terapia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
15.
Chemosphere ; 241: 125081, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31622890

RESUMO

To take an insight into the long-term accumulation of chromium (Cr) and cadmium (Cd) in school-age children living near an MWI and to assess their early renal impairment, we conducted a cross-sectional study in 2015. A total of 116 children from the exposure area and 122 from the control area were recruited. We measured the urinary levels of Cr (U-Cr) and Cd (U-Cd) by inductively coupled plasma mass spectrometry (ICP-MS), and detected three classic renal tubule indicators, including N-acetyl-ß-d-glucosaminidase (NAG), ß2-microglobulin (BMG), and retinol binding protein (RBP). The U-Cd and U-Cr levels in children living near the MWI were 0.11 and 1.57 µg/g creatinine, respectively. Both the U-Cd and U-Cr levels in the exposure group were lower than those in the control group, although only U-Cd showed a statistical difference (p < 0.01). The U-NAG and U-RBP levels in the exposure group were also statistically lower than those in the control group (0.80 vs. 1.74 IU/g creatinine, 0.26 vs. 0.48 mg/g creatinine, respectively). The U-Cd level in this study was positively correlated with the U-NAG level (r = 0.26, p < 0.01), as the U-Cr level was also positively correlated with the levels of U-NAG, U-RBP, and U-BMG (r = 0.21, 0.33, 0.18, p < 0.01, respectively). This study indicates that children living close to this particular MWI may not suffer considerable long-term accumulation of Cd or Cr, nor early renal impairment.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/urina , Incineração , Metais/urina , Acetilglucosaminidase/urina , Adulto , Cádmio/análise , Criança , Cromo , Creatinina/urina , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação ao Retinol , Microglobulina beta-2/urina
16.
Biomed Pharmacother ; 121: 109684, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810121

RESUMO

Nephrotoxicity is an important limitation to the clinical use of many drugs and contrast media. Drug nephrotoxicity occurs in acute, subacute and chronic manifestations ranging from glomerular, tubular, vascular and immunological phenotypes to acute kidney injury. Pre-emptive risk assessment of drug nephrotoxicity poses an urgent need of precision medicine to optimize pharmacological therapies and interventional procedures involving nephrotoxic products in a preventive and personalized manner. Biomarkers of risk have been identified in animal models, and risk scores have been proposed, whose clinical use is abated by their reduced applicability to specific etiological models or clinical circumstances. However, our present data suggest that the urinary level of transferrin may be indicative of risk of renal damage, where risk is induced by subclinical tubular alterations regardless of etiology. In fact, urinary transferrin pre-emptively correlates with the subsequent renal damage in animal models in which risk has been induced by drugs and toxins affecting the renal tubules (i.e. cisplatin, gentamicin and uranyl nitrate); whereas transferrin shows no relation with the risk posed by a drug affecting renal hemodynamics (i.e. cyclosporine A). Our experiments also show that transferrin increases in the urine in the risk state (i.e. prior to the damage) precisely as a consequence of reduced tubular reabsorption. Finally, urinary transferrin pre-emptively identifies subpopulations of oncological and cardiac patients at risk of nephrotoxicity. In perspective, urinary transferrin might be further explored as a wider biomarker of an important mechanism of predisposition to renal damage induced by insults causing subclinical tubular alterations.


Assuntos
Túbulos Renais/patologia , Transferrina/urina , Acetilglucosaminidase/urina , Animais , Biomarcadores/urina , Meios de Contraste/efeitos adversos , Creatinina/sangue , Suscetibilidade a Doenças , Feminino , Humanos , Nefropatias/induzido quimicamente , Nefropatias/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Platina/efeitos adversos , Ratos Wistar , Fatores de Risco , Ureia/sangue
17.
Congenit Heart Dis ; 14(6): 1087-1093, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31605509

RESUMO

OBJECTIVE: This study aims to investigate the changes in renal function and levels of urinary biomarkers before and after cardiac angiography in children with congenital heart disease (CHD). SETTING: Children with CHD are at a risk for kidney injury during contrast exposure in cardiac angiography. OUTCOME MEASURES: We measured urinary protein, albumin, N-acetyl-ß-D-glucosaminidase (NAG), ß2-microglobulin (BMG), and liver-type fatty acid-binding protein (L-FABP) levels, as well as serum creatinine and cystatin C levels, before and after cardiac angiography in 33 children with CHD. RESULTS: No significant decrease was noted in either the creatinine-based or cystatin C-based estimated glomerular filtration rate at 24 hours after angiography compared with that before angiography. Urinary protein, NAG, BMG, and L-FABP levels were significantly increased at 24 hours after angiography, all of which returned to baseline levels at more than 7 days after angiography. An increase in urinary level of protein, albumin, NAG, or BMG was mostly associated with increased urinary L-FABP level. An increase in both urinary BMG and L-FABP, but not that in urinary L-FABP alone, was associated with increased levels of urinary protein and NAG, as well as the greater dose of contrast media. CONCLUSIONS: Transient increases of kidney injury biomarkers following cardiac angiography are not necessarily associated with the impairment of renal function in a short time period; however, the increase in urinary protein, albumin, NAG, or BMG level may indicate greater stresses to the kidneys than the increase in urinary L-FABP alone in children with CHD.


Assuntos
Acetilglucosaminidase/urina , Injúria Renal Aguda/induzido quimicamente , Albuminúria/induzido quimicamente , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Proteínas de Ligação a Ácido Graxo/urina , Cardiopatias Congênitas/diagnóstico por imagem , Rim/efeitos dos fármacos , Microglobulina beta-2/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/urina , Adolescente , Fatores Etários , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Albuminúria/urina , Biomarcadores/urina , Criança , Feminino , Humanos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Regulação para Cima , Urinálise , Adulto Jovem
18.
J Perinatol ; 39(9): 1263-1267, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31316148

RESUMO

OBJECTIVE: The objective of this study is to compare glomerular and tubular functions in small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants. STUDY DESIGN: A prospective controlled study was conducted on SGA and AGA infants with gestational ages between 320/7 and 366/7 weeks, who received gentamycin in the first 72 h of life. Glomerular and tubular functions were assessed on days 1 and 5. RESULTS: Fifty (25 SGA and 25 AGA) infants were included. On day of life 1, SGA group had higher serum sodium, serum urea, and urinary creatinine. On day 5, SGA infants had significant increase in serum creatinine (p = 0.04). Urinary NAG and FeNa were comparable among the two groups on days 1 and 5. CONCLUSIONS: Glomerular functions were compromised in SGA preterm infants. Tubular functions were comparable.


Assuntos
Recém-Nascido Prematuro/fisiologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Rim/fisiologia , Acetilglucosaminidase/urina , Antibacterianos/uso terapêutico , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Creatinina/urina , Feminino , Gentamicinas/uso terapêutico , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Sódio/sangue , Sódio/urina , Ureia/sangue
19.
J Vet Diagn Invest ; 31(5): 688-695, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347464

RESUMO

Detection of equine acute kidney injury (AKI) is hindered by limited markers of early renal damage in horses. N-acetyl-ß-D-glucosaminidase (NAG), a lysosomal enzyme in renal tubular epithelium released into urine during tubular insult, has shown promise for early identification of AKI in humans and other species. We validated an assay for NAG in equine urine and measured urinary NAG in 7 azotemic and 7 non-azotemic client-owned adult horses. The enzymatic NAG assay was validated using within- and between-run coefficients of variation (CVs), recovery following standard addition, and linearity of dilution. Intra- and inter-run CVs (21% and 3.2%, respectively), average recovery following standard addition (99-109%), and linearity under serial dilution (R2 = 0.997) were satisfactory. Urine NAG index was significantly correlated with urinary fractional excretion of sodium (FENa; ρ = 0.76, p < 0.001) and plasma creatinine (ρ = 0.74, p = 0.001). Median urine NAG indices were higher in azotemic horses (p = 0.006), in horses with increased urinary FENa (p = 0.006), and in horses with increased urine gamma-glutamyl transferase index (p = 0.032). Urine NAG can be measured in horses and shows positive correlation with 2 current renal biomarkers. Additional work is needed to establish normal equine reference intervals and characterize the increase of urine NAG index in horses in relation to tubular injury.


Assuntos
Acetilglucosaminidase/urina , Injúria Renal Aguda/veterinária , Doenças dos Cavalos/diagnóstico , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Animais , Biomarcadores/urina , Creatinina/sangue , Feminino , Doenças dos Cavalos/urina , Cavalos , Humanos , Masculino , Sódio/urina , gama-Glutamiltransferase/urina
20.
BMC Nephrol ; 20(1): 186, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126255

RESUMO

BACKGROUND: The performance of urinary N-acetyl-ß-D-glucosaminidase (uNAG) for the detection of acute kidney injury (AKI) was controversial. uNAG is positively correlated with blood glucose levels. Hyperglycemia is common in the critically ill adults. The influence of blood glucose levels on the accuracy of uNAG in AKI detection has not yet been reported. The present study evaluated the effect of blood glucose levels on the diagnostic accuracy of uNAG to detect AKI. METHODS: A total of 1585 critically ill adults in intensive care units at three university hospitals were recruited in this prospective observational study. uNAG, serum glucose, and glycosylated hemoglobin (HbA1c) were measured at ICU admission. Patients were categorized based on the history of diabetes and blood glucose levels. The performance of uNAG to detect AKI in different groups was assessed by the area under the receiver operator characteristic curve. RESULTS: Four hundred and twelve patients developed AKI, of which 109 patients were severe AKI. uNAG was significantly correlated with the levels of serum glucose (P < 0.001) and HbA1c (P < 0.001). After stratification based on the serum glucose levels, no significant difference was observed in the AUC of uNAG in detecting AKI between any two groups (P > 0.05). Stratification for stress hyperglycemic demonstrated similar results.However, among non-diabetic patients, the optimal cut-off value of uNAG for detecting AKI was higher in stress hyperglycemic patients as compared to those without stress hyperglycemia. CONCLUSIONS: The blood glucose levels did not significantly affect the performance of uNAG for AKI detection in critically ill adults. However, the optimal cut-off value of uNAG to detect AKIwas affected by stress hyperglycemia in non-diabetic patients.


Assuntos
Acetilglucosaminidase/urina , Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Glicemia/metabolismo , Estado Terminal , Injúria Renal Aguda/diagnóstico , Adulto , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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