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1.
BMJ Open ; 10(9): e041983, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967887

RESUMO

OBJECTIVES: Being able to predict which patients with COVID-19 are going to deteriorate is important to help identify patients for clinical and research practice. Clinical prediction models play a critical role in this process, but current models are of limited value because they are typically restricted to baseline predictors and do not always use contemporary statistical methods. We sought to explore the benefits of incorporating dynamic changes in routinely measured biomarkers, non-linear effects and applying 'state-of-the-art' statistical methods in the development of a prognostic model to predict death in hospitalised patients with COVID-19. DESIGN: The data were analysed from admissions with COVID-19 to three hospital sites. Exploratory data analysis included a graphical approach to partial correlations. Dynamic biomarkers were considered up to 5 days following admission rather than depending solely on baseline or single time-point data. Marked departures from linear effects of covariates were identified by employing smoothing splines within a generalised additive modelling framework. SETTING: 3 secondary and tertiary level centres in Greater Manchester, the UK. PARTICIPANTS: 392 hospitalised patients with a diagnosis of COVID-19. RESULTS: 392 patients with a COVID-19 diagnosis were identified. Area under the receiver operating characteristic curve increased from 0.73 using admission data alone to 0.75 when also considering results of baseline blood samples and to 0.83 when considering dynamic values of routinely collected markers. There was clear non-linearity in the association of age with patient outcome. CONCLUSIONS: This study shows that clinical prediction models to predict death in hospitalised patients with COVID-19 can be improved by taking into account both non-linear effects in covariates such as age and dynamic changes in values of biomarkers.


Assuntos
Bilirrubina/sangue , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/mortalidade , Creatinina/sangue , Contagem de Linfócitos , Neutrófilos , Pneumonia Viral/mortalidade , Ureia/sangue , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Betacoronavirus , Biomarcadores/sangue , Estudos de Coortes , Infecções por Coronavirus/sangue , Feminino , Hospitalização , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Reino Unido
2.
Sci Rep ; 10(1): 14042, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820210

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator logistic regression model were used for selection of laboratory features. Seven laboratory features selected in the model were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicting outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/sangue , Modelos Estatísticos , Pneumonia Viral/sangue , Idoso , Bilirrubina/sangue , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Confiabilidade dos Dados , Estudos de Viabilidade , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Previsões/métodos , Humanos , Leucócitos , Aprendizado de Máquina , Masculino , Mioglobina/sangue , Pandemias , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Prognóstico , Protrombina/análise , Receptores de Interleucina-2/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Ureia/sangue
3.
PLoS One ; 15(6): e0233925, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32530952

RESUMO

It is important to calculate the drug removal by hemodialysis (HD) for drug dosing regimens in HD patients. However, there are limited and inconsistent information about the dialyzability of drugs by HD. Therefore, the aim of our study is to evaluate drug removal by utilizing a rat model of HD (HD rat) and to extrapolate this result to the drug removal rate in HD patients. HD rats received bilateral nephrectomy and HD for 2 h. The dialysis removal of 6 drugs was evaluated in HD rats. Dialysis efficiency, plasma protein binding rate (PBR) and distribution volume (Vd) of drugs were also measured. Furthermore, we examined the correlation between the dialyzability of drug in HD rats and humans and constructed the prediction formula of the drug dialyzability in HD patients. The clearance of urea and creatinine and normalized dialysis dose in HD rats were 0.83 ± 0.07 mL/min, 0.70 ± 0.08 mL/min, and 0.13 ± 0.06, respectively. The drug dialyzability in HD rats was similar to reported clinical data except for doripenem. A higher correlation was observed between drug dialyzability in reported clinical data and HD rats which were adjusted for PBR (r2 = 0.936; p < 0.001) compared to unadjusted (r2 = 0.812; p = 0.009). Therefore, we constructed the prediction formula of the drug dialyzability in HD patients by utilizing the HD rat model and PBR. This study is useful for evaluating the dialyzability of high-risk drugs in a clinical setting and might provide appropriate preclinical dialyzability data for new drug.


Assuntos
Preparações Farmacêuticas/sangue , Diálise Renal/métodos , Eliminação Renal , Animais , Creatina/sangue , Humanos , Masculino , Taxa de Depuração Metabólica , Modelos Animais , Farmacocinética , Ratos , Ratos Wistar , Ureia/sangue
4.
Int. j. morphol ; 38(3): 585-591, June 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1098291

RESUMO

Acetaminophen (also called paracetamol, or APAP) induced nephrotoxicity is reported after accidental or intentional ingestion of an overdose of the drug. Renal tubular ultrastructural alterations induced by APAP overdose associated with the induction of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic anti-inflammatory and antioxidants agents, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced acute kidney injury. The model group of rats received a single dose of APAP (2 g/kg), whereas the protective group of rats was pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP. All rats were then sacrificed one day post APAP ingestion. Harvested kidney tissues were prepared for transmission electron microscopy (TEM) staining and blood samples were assayed for urea, creatinine, and biomarkers of inflammation and oxidative stress. TEM images and blood chemistry analysis showed that APAP overdose induced kidney damage as demonstrated by substantial alterations to the proximal convoluted tubule ultrastructure, and a significant (p<0.05) increase in urea, creatinine, tumor necrosis factor-alpha (TNF-a), and malondialdehyde (MDA) blood levels, which were protected by RES+QUR. These findings indicate that APAP induces alterations to the renal tubular ultrastructure, which is inhibited by resveratrol plus quercetin, which also decreases blood levels of kidney injury biomarkers.


El objetivo de este trabajo fue estudiar la nefrotoxicidad inducida por acetaminofeno (también llamado paracetamol o APAP) después de la ingestión accidental o intencional de una sobredosis de la droga. Las alteraciones ultraestructurales tubulares renales inducidas por sobredosis de APAP asociadas con la inducción de biomarcadores de daño renal no se han investigado. Además, estudiamos si los agentes combinados antiinflamatorios y antioxidantes polifenólicos, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal aguda inducida por APAP. El grupo modelo de ratas recibió una dosis única de APAP (2 g / kg), mientras que el grupo protector de ratas se trató previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg) antes de recibir una dosis única de APAP. Todas las ratas se sacrificaron un día después de la ingestión de APAP. Los tejidos renales fueron preparados para el análisis a través de la microscopía electrónica de transmisión (MET). En las muestras de sangre se determinaron la urea, creatinina y los biomarcadores de inflamación y estrés oxidativo. Las imágenes MET y el análisis químico de la sangre mostraron que la sobredosis de APAP inducía daño renal, como lo demuestran las alteraciones sustanciales en la ultraestructura del túbulo contorneado proximal, y además, de un aumento significativo (p <0,05) de la urea, creatinina, factor de necrosis tumoral alfa y niveles sanguíneos de malondialdehído, protegidos por RES + QUR. Estos hallazgos indican que APAP induce alteraciones en la ultraestructura tubular renal, inhibida por el resveratrol más quercetina, que también disminuye los niveles sanguíneos de biomarcadores de daño renal.


Assuntos
Animais , Ratos , Quercetina/administração & dosagem , Resveratrol/administração & dosagem , Túbulos Renais/efeitos dos fármacos , Acetaminofen/toxicidade , Quercetina/farmacologia , Ureia/sangue , Ratos Sprague-Dawley , Creatinina/sangue , Microscopia Eletrônica de Transmissão , Modelos Animais de Doenças , Overdose de Drogas , Resveratrol/farmacologia , Túbulos Renais/patologia , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem
5.
Clin Chem Lab Med ; 58(7): 1100-1105, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32573995

RESUMO

Background Comprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity. Methods The final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge). Results Compared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death. Conclusions The most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , Glicemia/análise , Proteína C-Reativa/análise , Carnosina/sangue , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/fisiopatologia , Creatina Quinase/sangue , Creatinina/sangue , Combinação de Medicamentos , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio , Mortalidade Hospitalar , Humanos , Itália , L-Lactato Desidrogenase/sangue , Leucócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/fisiopatologia , Tempo de Protrombina , Albumina Sérica Humana/análise , Troponina I/sangue , Ureia/sangue
6.
Am J Physiol Renal Physiol ; 319(2): F162-F170, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32475132

RESUMO

A system for sorbent-assisted peritoneal dialysis (SAPD) was designed to continuously recirculate dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. We hypothesize that SAPD treatment will maintain a high plasma-to-dialysate concentration gradient and increase the mass transfer area coefficient of solutes. Thereby, the SAPD system may enhance clearance while reducing the number of exchanges. Application is envisaged at night as a bedside device (12 kg, nighttime system). A wearable system (2.0 kg, daytime system) may further enhance clearance during the day. Urea, creatinine, and phosphate removal were studied with the daytime and nighttime system (n = 3 per system) by recirculating 2 liters of spent peritoneal dialysate via a tidal mode (mean flow rate: 50 and 100 mL/min, respectively) for 8 h in vitro. Time-averaged plasma clearance over 24 h was modeled assuming one 2 liter exchange/day, an increase in mass transfer area coefficient, and 0.9 liters ultrafiltration/day. Urea, creatinine, and phosphate removal was 33.2 ± 4.1, 5.3 ± 0.5, and 6.2 ± 1.8 mmol, respectively, with the daytime system and 204 ± 28, 10.3 ± 2.4, and 11.4 ± 2.1 mmol, respectively, with the nighttime system. Time-averaged plasma clearances of urea, creatinine and phosphate were 9.6 ± 1.1, 9.6 ± 1.7, and 7.0 ± 0.9 mL/min, respectively, with the nighttime system and 10.8 ± 1.1, 13.4 ± 1.8, and 9.7 ± 1.6 mL/min, respectively, with the daytime and nighttime system. SAPD treatment may improve removal of uremic toxins compared with conventional peritoneal dialysis, provided that peritoneal mass transport will increase.


Assuntos
Creatinina/sangue , Soluções para Diálise/farmacologia , Diálise Peritoneal , Ureia/sangue , Humanos , Cinética , Peritônio/metabolismo , Fosfatos/sangue , Ultrafiltração/métodos
7.
PLoS One ; 15(5): e0233331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469929

RESUMO

Dialysis urea removal metrics may not translate into proportional removal efficiency of non-urea solutes. We show that the Kt factor (plasma volume totally cleared of any solutes) differentiates removal efficiency of non-urea solutes in different technologies, and can easily be calculated by instant blood-dialysate collections. We performed mass balances of urea, creatinine, phosphorus and beta2-microglobulin by whole dialysate collection in 4 low-flux and 3 high-flux hemodialysis, 2 high-volume post-hemodiafiltration and 7 short-daily dialysis with the NxStage-One system. Instant dialysate/blood determinations were also performed at different times, and Kt was calculated as the product of the D/P ratio by volume of delivered dialysate plus UF. There were significant differences in single session and weekly Kt (whole dialysate and instant calculations) between methodologies, most notably for creatinine, phosphorus and beta2-microglobulin. Urea Kt messured in balance studies was almost equal to that derived from the usual plasma kinetic model-based Daugirdas' equation (eKt/V) and independent V calculation, indicating full correspondence. Non-urea solute Kt as a fraction of urea Kt (i.e. fractional removal relative to urea) showed significant differences between technologies, indicating non-proportional removal of non-urea solutes and urea. Instant Kt was higher than that in full balances, accounting for concentration disequilibrium between arterial and systemic blood, but measured and calculated quantitative solute removal were equal, as were qualitative Kt comparisons between technologies. Thus, we show that urea metrics may not reliably express removal efficiency of non-urea solutes, as indicated by Kt. Kt can easily be measured without whole dialysate collection, allowing to expand the metrics of dialytic efficiency to almost any non-urea solute removed by dialysis.


Assuntos
Algoritmos , Hemodiafiltração/métodos , Soluções para Hemodiálise/análise , Monitorização Fisiológica/métodos , Diálise Renal/métodos , Ureia/sangue , Humanos , Cinética , Monitorização Fisiológica/instrumentação
8.
Pediatr Blood Cancer ; 67(8): e28209, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32472983

RESUMO

BACKGROUND: Patients with high-risk neuroblastoma (HR NBL) treated with myeloablative regimens are reported to be at risk for cardiovascular morbidity, and this risk may be increased by impaired renal function. PROCEDURE: Long-term renal function was assessed in a national cohort of 18 (age 22.4 ± 4.9 years) HR NBL survivors by plasma creatinine (P-Cr), urea, and cystatin C (P-Cys C) concentrations, urine albumin/creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Ambulatory blood pressure was monitored, and common carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) were evaluated. RESULTS: No significant difference in P-Cr, P-Cys C, or eGFR was found between the NBL survivors and the age- and sex-matched 20 controls. P-Cys C-based eGFR (eGFRcysc) was significantly lower than the P-Cr-based eGFRcr (97 ± 17 mL/min/1.73 m2 vs 111 ± 19 mL/min/1.73 m2 , P < 0.001) among the NBL survivors. The eGFRcysc was below normal in 28%, and ACR was above normal in 22% of the NBL survivors. Abnormal blood pressure was found in 56% of the survivors, and an additional 17% were normotensive at daytime but had significant nocturnal hypertension. Both ACR and P-Cys C were associated with nighttime diastolic hypertension. CONCLUSIONS: Long-term survivors of childhood HR NBL showed signs of only mild renal dysfunction associated with diastolic hypertension. Elevated ACR and P-Cys C were the most sensitive indicators of glomerular renal dysfunction and hypertension in this patient cohort.


Assuntos
Sobreviventes de Câncer , Hipertensão , Testes de Função Renal , Neuroblastoma , Adolescente , Adulto , Creatinina/sangue , Cistatina C/sangue , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Masculino , Neuroblastoma/sangue , Neuroblastoma/terapia , Ureia/sangue
11.
Artigo em Chinês | MEDLINE | ID: mdl-32306632

RESUMO

Objective: To analyze the factors affecting olfactory disfunctions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: This was a retrospective analysis. Eighty-eight patients with CRSwNP who underwent endoscopic sinus surgery in Beijing Anzhen Hospital from 2014 to 2018 were enrolled, including 22 males and 66 females, with the age of (48.1±11.3) years old(Mean±SD). Sniffin' Sticks olfactory test, Lund-Mackay score and modified sinus CT olfactory cleft score, nasal resistance and acoustic reflex examination, blood routine and blood biochemistry test, serum specific IgE test were performed before surgery and nasal polyps of all patients were collected for eosinophil count during surgery. According to bilateral total TDI score, the patients were divided into normal olfactory function group and olfactory disfunction group. The clinical baseline data were compared between the two groups. According to the results of single factor analysis, factors which were significant different between the two groups and clinically useful indicators were further included in the multivariate Logistic regression model analysis, then a model predicting olfactory disfunction in patients with CRSwNP was initially established. P<0.05 was considered statistically significant. Results: Among 88 patients with CRSwNP, 32 (36.4%) patients were with normal olfaction and 56 (63.6%) patients were with olfactory disfunction, including 40 (45.5%) of hyposmia and 16 (18.2%) of anosmia. Tissue eosinophil count, blood eosinophil percentage and blood urea concentration had significant difference between the two groups (12.7[2.0, 52.3]/HP (M[P(25), P(75)]) vs 38.6[16.2, 87.0]/HP, 2.75[1.60, 4.80]% vs 4.35[2.50, 6.60]%, (5.56±1.15) mmol/L vs (4.98±1.33) mmol/L, all P<0.05). Modified sinus CT olfactory cleft score and Lund-Mackay score except for ostiomeatal complex score were statistically significant between the two groups (all P<0.05). Multivariate Logistic regression analysis showed that the bilateral and total olfactory cleft score and blood urea concentration were statistically significant, in addition, the bilateral and total olfactory cleft score was a risk factor (OR=2.108, 95%CI: 1.407-3.159, P<0.001) and blood urea within a certain concentration was a protective factor (OR=0.461, 95%CI: 0.240-0.884, P=0.020). Further studies found that the area under the ROC curve of the model with tissue eosinophil count, blood eosinophil percentage, bilateral and total olfactory cleft score, total inspiratory volume and blood urea concentration was 0.888 (P<0.01), which had good predictive value for olfactory disorders in CRSwNP. Conclusions: The modified sinus CT olfactory cleft score is closely related to the olfactory disorders in patients with CRSwNP. A certain degree of elevated blood urea concentration may have a protective effect on the olfactory function of patients with CRSwNP.


Assuntos
Pólipos Nasais/complicações , Transtornos do Olfato/etiologia , Rinite/complicações , Sinusite/complicações , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seios Paranasais/diagnóstico por imagem , Estudos Retrospectivos , Olfato , Tomografia Computadorizada por Raios X , Ureia/sangue
12.
PLoS One ; 15(4): e0231017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32255772

RESUMO

BACKGROUND: Locally established clinical laboratory reference intervals (RIs) are required to interpret laboratory test results for screening, diagnosis and prognosis. The objective of this study was establishing reference interval of clinical chemistry parameters among apparently healthy adolescents aged between 12 and 17 years in Mekelle, Tigrai, northern part of Ethiopia. METHODS: Community based cross sectional study was employed from December 2018 to March 2019 in Mekelle city among 172 males and 172 females based on Multi stage sampling technique. Blood samples were tested for Fasting blood sugar (FBS), alanine aminino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), Creatinine, urea, total protein, albumin (ALB), direct and indirect bilirubin (BIL.D and BIL.T) using 25 Bio system clinical chemistry analyzer. Results were analyzed using SPSS version 23 software and based on the Clinical Laboratory Standard Institute (CLSI)/ International Federation of Clinical Chemistry (IFCC) C 28-A3 Guideline which defines the reference interval as the 95% central range of 2.5th and 97.5th percentiles. Mann Whitney U test, descriptive statistics and box and whisker were statistical tools used for analysis. RESULTS: This study observed statistically significant differences between males and females in ALP, ALT, AST, Urea and Creatinine Reference intervals. The established reference intervals for males and females, respectively, were: ALP (U/L) 79.48-492.12 versus 63.56-253.34, ALT (U/L) 4.54-23.69 versus 5.1-20.03, AST 15.7-39.1 versus 13.3-28.5, Urea (mg/dL) 9.33-24.99 versus 7.43-23.11, and Creatinine (mg/dL) 0.393-0.957 versus 0.301-0.846. The combined RIs for Total Protein (g/dL) was 6.08-7.85, ALB (g/dL) 4.42-5.46, FBS(mg/dL) 65-110, BIL.D (mg/dL) 0.033-0.532, and BIL.T (mg/dL) 0.106-0.812. CONCLUSIONS: The result showed marked difference among sex and with the company derived values for selected clinical chemistry parameters. Thus, use of age and sex specific locally established reference intervals for clinical chemistry parameters is recommended.


Assuntos
Química Clínica/normas , Adolescente , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Glicemia/análise , Proteínas Sanguíneas/análise , Criança , Creatinina/sangue , Estudos Transversais , Etiópia , Feminino , Humanos , Masculino , Valores de Referência , Albumina Sérica/análise , Ureia/sangue
13.
PLoS One ; 15(3): e0230002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160250

RESUMO

INTRODUCTION: Severe aortic stenosis (AS) is the most common valvular heart disease in the western world. Various factors are related to severe AS prognosis, including chronic kidney disease. The aim of this study was to evaluate the prognostic value of urea level in patients with severe AS. METHODS: We prospectively enrolled 142 patients (79.1±9.4 years, 88 women) with severe AS (mean valve area 0.67± 0.17 cm2). Clinical assessment, blood tests and echocardiography were performed at enrollment and follow up. The patient population was divided into low and high urea level groups, according to the median urea level at enrollment (72 patients, mean urea 35.5±6.2 mg/dL and 70 patients, mean urea 61.1±17.8 mg/dL, respectively). Hundred and twelve patients (79%) underwent aortic valve intervention. The primary endpoint was all-cause and cardiovascular mortality. OUTCOMES: During follow-up of 37±19.5 months, 56 (37.1%) patients died, 39 due to cardiovascular causes. In univariate analysis, age, urea level, creatinine, New York Heart Association (NYHA) class and aortic valve intervention were associated with all-cause mortality. However, in multivariate analysis only aortic valve intervention and blood urea were independent predictors of all-cause mortality (HR 0.494; 95% CI 0.226-0.918, P = 0.026 and HR 1.015; 95% CI 1.003-1.029, P = 0.046 respectively). Urea level, NYHA class and age were also significant predictors of cardiovascular mortality. Whereas, in multivariate analysis, only urea level predicted cardiovascular mortality in these patients (HR 1.017; CI 1.003-1.031 P = 0.019). CONCLUSIONS: Blood urea, a generally readily available and routinely determined marker of renal function, is an independent prognostic factor in patients with severe AS.


Assuntos
Estenose da Valva Aórtica/patologia , Doenças Cardiovasculares/mortalidade , Ureia/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/patologia , Estenose da Valva Aórtica/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Intervalo Livre de Doença , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Taxa de Sobrevida
14.
Am J Physiol Gastrointest Liver Physiol ; 318(5): G912-G927, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32174131

RESUMO

Glucagon regulates the hepatic amino acid metabolism and increases ureagenesis. Ureagenesis is activated by N-acetylglutamate (NAG), formed via activation of N-acetylglutamate synthase (NAGS). With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we investigated whether glucagon receptor-mediated activation of ureagenesis is required in a situation where NAGS activity and/or NAG levels are sufficient to activate the first step of the urea cycle in vivo. Female C57BL/6JRj mice treated with a glucagon receptor antagonist (GRA), glucagon receptor knockout (Gcgr-/-) mice, and wild-type (Gcgr+/+) littermates received an intraperitoneal injection of N-carbamoyl glutamate (Car; a stable variant of NAG), l-citrulline (Cit), Car and Cit (Car + Cit), or PBS. In separate experiments, Gcgr-/- and Gcgr+/+ mice were administered N-carbamoyl glutamate and l-citrulline (wCar + wCit) in the drinking water for 8 wk. Car, Cit, and Car + Cit significantly (P < 0.05) increased plasma urea concentrations, independently of pharmacological and genetic disruption of glucagon receptor signaling (P = 0.9). Car increased blood glucose concentrations equally in GRA- and vehicle-treated mice (P = 0.9), whereas the increase upon Car + Cit was impaired in GRA-treated mice (P = 0.008). Blood glucose concentrations remained unchanged in Gcgr-/- mice upon Car (P = 0.2) and Car + Cit (P = 0.9). Eight weeks administration of wCar + wCit did not change blood glucose (P > 0.2), plasma amino acid (P > 0.4), and urea concentrations (P > 0.3) or the area of glucagon-positive cells (P > 0.3) in Gcgr-/- and Gcgr+/+ mice. Our data suggest that glucagon-mediated activation of ureagenesis is not required when NAGS activity and/or NAG levels are sufficient to activate the first step of the urea cycle.NEW & NOTEWORTHY Hepatic ureagenesis is essential in amino acid metabolism and is importantly regulated by glucagon, but the exact mechanism is unclear. With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we here show, contrary to our hypothesis, that glucagon receptor-mediated activation of ureagenesis is not required when N-acetylglutamate synthase activity and/or N-acetylglutamate levels are sufficient to activate the first step of the urea cycle in vivo.


Assuntos
Citrulina/administração & dosagem , Glucagon/metabolismo , Glutamatos/administração & dosagem , Fígado/efeitos dos fármacos , Receptores de Glucagon/deficiência , Receptores de Glucagon/metabolismo , Ureia/sangue , Aminoácido N-Acetiltransferase/metabolismo , Animais , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Feminino , Glutamatos/metabolismo , Antagonistas de Hormônios/administração & dosagem , Fígado/enzimologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Glucagon/antagonistas & inibidores , Receptores de Glucagon/genética
15.
Scand J Immunol ; 91(5): e12868, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32052490

RESUMO

Renal dysfunctions are major predictors of co-morbidities and mortality in HIV-infected individuals. Unconventional T cells have been shown to regulate kidney functions. However, there is dearth of information on the effect of HIV-associated nephropathies on γδ and DN T cells. It is also not clear whether γδ T cell perturbations observed during the early stages of HIV infection occur before immune activation. In this study, we investigated the relationship between creatinine and urea on the number of unconventional T cells in HIV-infected individuals at the early and chronic stages of infection. Persons in the chronic stage of infection were divided into treatment naïve and exposed groups. Treatment exposed individuals were further subdivided into groups with undetectable and detectable HIV-1RNA in their blood. Creatinine and urea levels were significantly higher among persons in the early HIV infection compared with the other groups. Proportions of γδ T, γδ + CD8, γδ + CD16 cells were also significantly reduced in the early stage of HIV infection (P < .01). Markers of immune activation, CD4 + HLA-DR and CD8 + HLA-DR, were also significantly reduced during early HIV infection (P < .01). Taken together, our findings suggest that high levels of renal markers as well as reduced proportions of gamma delta T cells are associated with the early stages of HIV infection. This event likely occurs before systemic immune activation reaches peak levels. This study provides evidence for the need for early HIV infection diagnosis and treatment.


Assuntos
Creatinina/sangue , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Ureia/sangue , Adulto , Biomarcadores , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Imunofenotipagem , Nefropatias/etiologia , Nefropatias/fisiopatologia , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Neutrófilos , Fatores de Tempo , Carga Viral , Adulto Jovem
16.
Oxid Med Cell Longev ; 2020: 5478708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32082479

RESUMO

Kidney disease represents a serious global health problem. One of the main concerns is its late diagnosis, only feasible in a progressed disease state. The lack of a clinical manifestation in the early stages and the fact that the commonly measured parameters of renal function are markedly reduced only during advanced stages of the disease are the main cause. Changes at the molecular level of the kidney tissue occur even before nitrogenous substances, such as creatinine and urea, start to accumulate in the blood. Renal proximal tubules contain a large number of mitochondria and are critical for the energy-demanding process of reabsorption of water and solutes. Mitochondria are the largest producers of oxygen radicals, which, in turn, increase the susceptibility of kidneys to oxidative stress-induced damage. Free radicals and prooxidants produced during acute or chronic kidney injury may further aggravate the course of the disease and play a role in the pathogenesis of subsequent complications. Prevention might be the solution in CKD, but patients are often reluctant to undergo preventive examinations. Noninvasive markers and the possibility to obtain samples at home might help to increase compliance. This review will provide an overview of the possible uses of markers of oxidative status in noninvasive biofluids in patients with renal disease.


Assuntos
Lesão Renal Aguda/metabolismo , Biomarcadores/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/metabolismo , Lesão Renal Aguda/enzimologia , Lesão Renal Aguda/fisiopatologia , Animais , Citocinas/metabolismo , Glutationa/sangue , Humanos , Inflamação/metabolismo , Túbulos Renais Proximais/metabolismo , Insuficiência Renal Crônica/enzimologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Ureia/sangue
17.
Nutrients ; 12(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028696

RESUMO

Low and high plasma glutamine levels are associated with increased mortality. This study aimed to measure glutamine levels in critically ill patients admitted to the intensive care unit (ICU) , correlate the glutamine values with clinical outcomes, and identify proxy indicators of abnormal glutamine levels. Patients were enrolled from three ICUs in South Africa, provided they met the inclusion criteria. Clinical and biochemical data were collected. Plasma glutamine was categorized as low (<420 µmol/L), normal (420-700 µmol/L), or high (>700 µmol/L). Three hundred and thirty patients (median age 46.8 years, 56.4% male) were enrolled (median APACHE II score) 18.0 and SOFA) score 7.0). On admission, 58.5% had low (median 299.5 µmol/L) and 14.2% high (median 898.9 µmol/L) plasma glutamine levels. Patients with a diagnosis of polytrauma and sepsis on ICU admission presented with the lowest, and those with liver failure had the highest glutamine levels. Admission low plasma glutamine was associated with higher APACHE II scores (p = 0.003), SOFA scores (p = 0.003), C-reactive protein (CRP) values (p < 0.001), serum urea (p = 0.008), and serum creatinine (p = 0.023) and lower serum albumin (p < 0.001). Low plasma glutamine was also associated with requiring mechanical ventilation and receiving nutritional support. However, it was not significantly associated with length of stay or mortality. ROC curve analysis revealed a CRP threshold value of 87.9 mg/L to be indicative of low plasma glutamine levels (area under the curve (AUC) 0.7, p < 0.001). Fifty-nine percent of ICU patients had low plasma glutamine on admission, with significant differences found between diagnostic groupings. Markers of infection and disease severity were significant indicators of low plasma glutamine.


Assuntos
Cuidados Críticos , Estado Terminal , Glutamina/sangue , Unidades de Terapia Intensiva , Adulto , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Creatinina/sangue , Feminino , Mortalidade Hospitalar , Humanos , Infecções/sangue , Falência Hepática/sangue , Masculino , Pessoa de Meia-Idade , Apoio Nutricional , Curva ROC , Respiração Artificial , Sepse/sangue , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , África do Sul , Ureia/sangue
18.
J Zoo Wildl Med ; 50(4): 927-936, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926525

RESUMO

Seabirds have been widely used for monitoring the health of the oceans in diverse marine regions. Among low-cost survey strategies, systematic surveys of seabirds beached on coasts have been developed since the 20th century. However, these studies do not always address blood aspects. The assessment of the health status of birds based on the analysis of hematological and plasma chemistry is crucial to evaluate the overall health status profile of live organisms. Here, the authors study the variability of blood parameters by sex, age class, and year of beached Magellanic Penguin during the nonreproductive period in northern Argentina. Of 44 penguins, 77% were categorized as younger juveniles and the rest as older juveniles, and were captured and studied in coastal areas of Buenos Aires Province during the summers of 2017 and 2018. The mean body weight of beached penguins was affected by the age class of the individuals; most of the younger juveniles showed poor condition in terms of body mass (1,761 ± 235 g). No significant differences were observed in body weight between years and sex. Still, there were significant differences between years for alkaline phosphatase (ALP) and creatine phosphokinase (CPK) values. Twelve of the 20 blood parameters analyzed differ significantly with the age class of the beached penguins; younger juveniles were in a state of inanition. Our results may serve as a necessary first step in improving the conservation status of the Magellanic Penguin in nonbreeding grounds of Argentina, and call for a better knowledge of the health status of the species along its annual cycle.


Assuntos
Contagem de Eritrócitos/veterinária , Hematócrito , Contagem de Leucócitos/veterinária , Estações do Ano , Spheniscidae/sangue , Envelhecimento , Fosfatase Alcalina/sangue , Animais , Animais Selvagens , Anticorpos Heterófilos , Argentina , Glicemia , Proteínas Sanguíneas , Colesterol/sangue , Creatina Quinase/sangue , Feminino , Hemoglobinas , Contagem de Linfócitos/veterinária , Masculino , Fósforo/sangue , Transaminases/sangue , Ureia/sangue , Ácido Úrico/sangue
19.
Life Sci ; 242: 117239, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31901444

RESUMO

AIMS: Reactive oxygen species (ROS) and pro-inflammatory cytokines play a critical role in organ damage induced by ethanol consumption. Interleukin (IL)-10 maintain tissue homeostasis through restriction of excessive inflammatory responses and inhibition of ROS generation. These responses limit unnecessary tissue damage in the cardiorenal system. We hypothesized that IL-10 would limit the deleterious effects induced by ethanol consumption in the cardiorenal system. MATERIALS AND METHODS: Male C57BL/6J wild-type (WT) or IL10-deficient mice (IL-10-/-) were treated with ethanol (20% v/v) for 6 weeks. KEY FINDINGS: IL-10 deficiency was associated with an increased mortality rate. Ethanol consumption decreased plasma levels of IL-10 in WT mice. Increased levels of IL-6 were detected in the aorta from IL-10-deficient mice, but not WT mice. No alterations in the levels of urea, creatinine, sodium, potassium or creatine kinase (CK)-MB were found after treatment with ethanol. Augmented concentration of thiobarbituric acid reactive substances (TBARS) was found in the left ventricle (LV) of IL-10-deficient mice, but not WT mice. Increased levels of superoxide anion (O2-) were found in the renal cortex of both WT and IL-10-deficient mice. Renal cortex from WT mice chronically treated with ethanol showed decreased levels of H2O2. No changes in the expression of Nox1, Nox4 or catalase were found in the renal cortex from ethanol-treated mice. SIGNIFICANCE: IL-10 limited the production of ROS and the synthesis of pro-inflammatory cytokines induced by ethanol in the cardiorenal system. These findings provided novel evidence that IL-10 counteracted the initial mechanisms whereby ethanol induces its cardiorenal damages.


Assuntos
Etanol/efeitos adversos , Coração/efeitos dos fármacos , Interleucina-10/metabolismo , Rim/efeitos dos fármacos , Lesão Renal Aguda/induzido quimicamente , Animais , Western Blotting , Creatina Quinase Forma MB/sangue , Creatinina/sangue , Interleucina-10/sangue , Interleucina-10/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Potássio/sangue , Sódio/sangue , Ureia/sangue
20.
Clin Nephrol ; 93(2): 65-76, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31793871

RESUMO

OBJECTIVE: The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers. MATERIALS AND METHODS: This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr). RESULTS: Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D. CONCLUSION: UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/urina , Creatinina/urina , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Biomarcadores/urina , Cálcio/sangue , Estudos de Casos e Controles , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Creatinina/sangue , Estudos Transversais , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Glucuronidase/sangue , Humanos , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Minerais/metabolismo , Hormônio Paratireóideo/sangue , Fósforo/sangue , Insuficiência Renal Crônica/fisiopatologia , Ureia/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
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