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1.
Ann Lab Med ; 42(2): 178-187, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635611

RESUMO

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however, its clinical impact in the emergency department (ED) remains unproven. We evaluated the utility of NephroCheck for predicting AKI development and short-term mortality in the ED. Methods: This was a prospective, observational, five-center international study. We consecutively enrolled ED patients admitted with ≥30% risk of AKI development (assessed by ED physician: ED score) or acute diseases. Serum creatinine was tested on ED arrival (T0), day 1, and day 2 (T48); urine for NephroCheck was collected at T0 and T48. We performed ROC curve and reclassification analyses. Results: Among the 529 patients enrolled (213 females; median age, 65 years), AKI developed in 59 (11.2%) patients. The T0 NephroCheck value was higher in the AKI group than in the non-AKI group (median 0.77 vs. 0.29 (ng/m)2/1,000, P=0.001), and better predicted AKI development than the ED score (area under the curve [AUC], 0.64 vs. 0.53; P=0.04). In reclassification analyses, adding NephroCheck to the ED score improved the prediction of AKI development (P<0.05). The T0 NephroCheck value predicted 30-day mortality (AUC, 0.68; P<0.001). Conclusions: NephroCheck can predict both AKI development and short-term mortality in at-risk ED patients. NephroCheck would be a useful biomarker for early ruling-in or ruling-out of AKI in the ED.


Assuntos
Injúria Renal Aguda , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2 , Doença Aguda , Injúria Renal Aguda/diagnóstico , Idoso , Biomarcadores , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/urina , Estados Unidos
2.
Arch. pediatr. Urug ; 92(2): e307, dic. 2021. ilus, tab
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1339135

RESUMO

Las porfirias son un grupo complejo y heterogéneo de defectos en la vía de la síntesis del hemo. La porfiria hepato eritropoyética es un subtipo muy poco frecuente y de presentación en la infancia, con compromiso cutáneo predominante. Describimos el caso clínico de una paciente de 5 años, que se presenta con lesiones cutáneas e hipertricosis, se confirma el diagnóstico por elevación de uroporfirinas en orina y secuenciación del gen UROD.


Porphyria is a complex and heterogeneous group of heme synthesis disorder. Hepato-erythropoietic porphyria is a very rare subtype that onsets in childhood, and shows predominant skin involvement. We describe the clinical case of a 5-year-old patient who showed skin lesions and hypertrichosis and whose diagnosis was confirmed due to increased uroporphyrins in urine and UROD gene sequencing


A porfiria é um grupo complexo e heterogêneo de distúrbios da síntese do grupo heme. A porfiria hepato-eritropoiética é um subtipo muito raro que se inicia na infância e mostra envolvimento predominante da pele. Descrevemos o caso clínico de uma paciente de 5 anos que apresentou lesões cutâneas e hipertricose e cujo diagnóstico foi confirmado por aumento de uroporfirinas na urina e sequenciamento do gene UROD.


Assuntos
Humanos , Feminino , Pré-Escolar , Vesícula/etiologia , Porfiria Hepatoeritropoética/complicações , Porfiria Hepatoeritropoética/genética , Porfiria Hepatoeritropoética/urina , Diabetes Mellitus Tipo 1/complicações , Hipertricose/etiologia , Uroporfirinogênio Descarboxilase/análise , Uroporfirinas/urina , Vesícula/tratamento farmacológico , Coproporfirinas/urina , Hipertricose/tratamento farmacológico
3.
BMC Nephrol ; 22(1): 381, 2021 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774005

RESUMO

BACKGROUND: Kidney dysfunction occurs in severe COVID-19, and is a predictor of COVID-19 mortality. Whether kidney dysfunction causes severe COVID-19, and hence is a target of intervention, or whether it is a symptom, is unclear because conventional observational studies are open to confounding. To obtain unconfounded estimates, we used Mendelian randomization to examine the role of kidney function in severe COVID-19. METHODS: We used genome-wide significant, uncorrelated genetic variants to predict kidney function, in terms of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), and then assessed whether people with genetically instrumented higher eGFR or lower UACR, an indication of better kidney function, had a lower risk of severe COVID-19 (8779 cases, 1,001,875 controls), using the largest available cohorts with extensive genotyping. For comprehensiveness, we also examined their role in COVID-19 hospitalization (24,274 cases, 2,061,529 controls) and all COVID-19 (1,12,612 cases, 2,474,079 controls). RESULTS: Genetically instrumented higher eGFR was associated with lower risk of severe COVID-19 (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.83, 0.98) but not related to COVID-19 hospitalization or infection. Genetically instrumented UACR was not related to COVID-19. CONCLUSIONS: Kidney function appears to be one of the key targets for severe COVID-19 treatment. Use of available medications to improve kidney function, such as antihypertensives, might be beneficial for COVID-19 treatment, with relevance to drug repositioning.


Assuntos
COVID-19/complicações , COVID-19/genética , Taxa de Filtração Glomerular/genética , Rim/fisiopatologia , Gravidade do Paciente , Albuminúria/urina , Estudos de Casos e Controles , Creatinina/urina , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética , Estudo de Associação Genômica Ampla , Hospitalização , Humanos , Análise da Randomização Mendeliana , Fatores de Risco , SARS-CoV-2
4.
Pan Afr Med J ; 40: 75, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804342

RESUMO

Introduction: metabolic abnormalities are key factors in urolithiasis patients because they can be modified to prevent the risk of urinary stones. The objectives of this study were to estimate the frequency of metabolic abnormalities in the urine of patients with urolithiasis and to determine their possible link with the chemical composition of stones. Methods: we conducted a cross-sectional study evaluating 73 patients referred for urolithiasis in 8 clinics in Kinshasa, between January 2017 and September 2019. Twenty four-hour or early morning urine were collected and analyzed in the Tenon Hospital in Paris. Parameters analyzed included pH, specific gravity, creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. Chi square test or chi-square likelihood-ratio and student's t test were used as statistical tests. Results: overall, 89% (n=65) of patients with lithiasis had metabolic abnormalities. Mean (SD) age of patients was 47.0 (14.2) years with male to female ratio of 1.6: 1. The mean (SD) 24-hour diuresis was 1836.4 (1216.9) ml; the mean (SD) urine density was 1.018 (0.007); and the mean (SD) pH was 6.1(0.8). Hypocitraturia was the most frequently observed metabolic abnormality and was found in 76.7% patients. Other significant metabolic abnormalities were low magnesuria (35.6%), hyperoxaluria (11%), and low sulphaturia (74%). Whewellite (73.5%) was the main chemical component. The mean pH was higher in patients with carbapatite and struvite stones (p=0.031). Conclusion: this study suggests that inadequate diuresis and hypocitraturia were important lithogenic factors. The population should be encouraged to increase water intake to limit the frequency of urine super saturation with crystals.


Assuntos
Cálculos Urinários/química , Urina/química , Urolitíase/epidemiologia , Adulto , Ácido Cítrico/urina , Estudos Transversais , República Democrática do Congo , Diurese/fisiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
5.
Biosensors (Basel) ; 11(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34821635

RESUMO

The measurement of cysteine in human urine and live cells is crucial for evaluating biological metabolism, monitoring and maintaining the immune system, preventing tissue/DNA damage caused by free radicals, preventing autoimmune diseases, and diagnosing disorders such as cystinuria and cancer. A method that uses a fluorescence turn-on probe and a portable fluorescence spectrometer device are crucial for highly sensitive, simple, rapid, and inexpensive cysteine detection. Herein, we present the synthesis and application of a benzimidazole-based fluorescent probe (ABIA) along with the design and development of a portable fluorescence spectrometer device (CysDDev) for detecting cysteine in simulated human urine. ABIA showed excellent selectivity and sensitivity in detecting cysteine over homocysteine, glutathione, and other amino acids with the response time of 1 min and demonstrated a detection limit of 16.3 nM using the developed CysDDev. Further, ABIA also demonstrated its utility in detecting intracellular cysteine, making it an excellent probe for bio-imaging assay.


Assuntos
Cisteína , Corantes Fluorescentes , Benzimidazóis , Cisteína/urina , Glutationa , Humanos , Espectrometria de Fluorescência
6.
Nutrients ; 13(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34684574

RESUMO

An herbal mixture composed of lemon, apple cider, garlic, ginger and honey as a polyphenol-rich mixture (PRM) has been reported to contain hypolipidemic activity on human subjects and hyperlipidemic rats. However, the therapeutic effects of PRM on metabolites are not clearly understood. Therefore, this study aimed to provide new information on the causal impact of PRM on the endogenous metabolites, pathways and serum biochemistry. Serum samples of hyperlipidemic rats treated with PRM were subjected to biochemistry (lipid and liver profile) and hydroxymethylglutaryl-CoA enzyme reductase (HMG-CoA reductase) analyses. In contrast, the urine samples were subjected to urine metabolomics using 1H NMR. The serum biochemistry revealed that PRM at 500 mg/kg (PRM-H) managed to lower the total cholesterol level and low-density lipoprotein (LDL-C) (p < 0.05) and reduce the HMG-CoA reductase activity. The pathway analysis from urine metabolomics reveals that PRM-H altered 17 pathways, with the TCA cycle having the highest impact (0.26). Results also showed the relationship between the serum biochemistry of LDL-C and HMG-CoA reductase and urine metabolites (trimethylamine-N-oxide, dimethylglycine, allantoin and succinate). The study's findings demonstrated the potential of PRM at 500 mg/kg as an anti-hyperlipidemic by altering the TCA cycle, inhibiting HMG-CoA reductase and lowering the LDL-C in high cholesterol rats.


Assuntos
Citrus/química , Alho/química , Gengibre/química , Mel , Hiperlipidemias/metabolismo , Hiperlipidemias/terapia , Malus/química , Metaboloma , Preparações de Plantas/uso terapêutico , Animais , Hidroximetilglutaril-CoA Redutases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipidemias/sangue , Hiperlipidemias/urina , Análise dos Mínimos Quadrados , Lipoproteínas LDL/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Polifenóis/farmacologia , Análise de Componente Principal , Espectroscopia de Prótons por Ressonância Magnética , Ratos Wistar
7.
Sci Rep ; 11(1): 19675, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608231

RESUMO

Kidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney's critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.


Assuntos
Injúria Renal Aguda/patologia , Biomarcadores/urina , COVID-19/imunologia , Insuficiência Renal Crônica/patologia , Injúria Renal Aguda/complicações , Adulto , Idoso , Antígenos CD/urina , Biomarcadores/sangue , Antígeno Ca-125/urina , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Quimiocinas CC/sangue , Estudos Transversais , Feminino , Humanos , Interleucina-12/urina , Interleucina-6/sangue , Masculino , Proteínas de Membrana/urina , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Insuficiência Renal Crônica/complicações , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/sangue
8.
PLoS One ; 16(10): e0257331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34634050

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a multi-faceted gastrointestinal disorder where food intake often triggers symptoms. Metabolomics may provide mechanistical insights to why responses to dietary modifications are diverse. OBJECTIVE: This study aimed to identify metabolite patterns related to dietary intake in patients with IBS, and to identify metabolites driving the separation between responders and non-responders to treatment. METHODS: Participants were randomized to a low fermentable oligo-, di-, monosaccharide and polyol (FODMAP) diet (LFD) or traditional IBS diet (TID) for four weeks. Fasting serum and urine samples pre- and post-intervention were analyzed using 1H nuclear magnetic resonance (NMR) metabolomics. Response to treatment was defined as a reduction in IBS severity scoring system (IBS-SSS) ≥50. RESULTS: Twenty-five individuals in the LFD (13 responders) and 28 in the TID (14 responders) were included in these post hoc analyses. In endpoint samples, significant decreases in polyols and glucose were seen in the LFD. Post-intervention samples revealed that LFD responders had significantly increased levels of 2-hydroxybuturate and decreased levels of glucose and pantothenic acid compared to non-responders. For the TID, only weak multivariate models were identified and a larger diversity in metabolite response compared to the LFD were noted. CONCLUSIONS: In this study, metabolite patterns between individuals who responded well to an LFD compared to non-responders could be distinguished. This provides new hypotheses for mechanistic actions related to response to dietary modifications, but the results need to be validated in larger cohorts. CLINICAL TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov, registry number NCT02107625.


Assuntos
Síndrome do Intestino Irritável/dietoterapia , Metaboloma , Adulto , Idoso , Dieta com Restrição de Carboidratos , Feminino , Fermentação , Humanos , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/urina , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
9.
Pediatrics ; 148(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34599008

RESUMO

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.


Assuntos
Injúria Renal Aguda , Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Biomarcadores/urina , Cafeína/uso terapêutico , Humanos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Recém-Nascido , Recém-Nascido Prematuro , Rim/efeitos dos fármacos , Rim/fisiologia , Lipocalina-2/urina , Estudos Multicêntricos como Assunto , Consumo de Oxigênio , Terapia de Substituição Renal/instrumentação , Pesquisa , Fatores de Risco , Teofilina/uso terapêutico , Equilíbrio Hidroeletrolítico
10.
J Med Microbiol ; 70(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34596013

RESUMO

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways.Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load.Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF.Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine.Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly (P<0.001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P=0.003).Conclusion. In adults with CF, AQ concentrations correlated more strongly with live P. aeruginosa bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of P. aeruginosa bacterial burden.


Assuntos
4-Quinolonas/isolamento & purificação , Fibrose Cística/complicações , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/isolamento & purificação , Percepção de Quorum , 4-Quinolonas/sangue , 4-Quinolonas/urina , Adolescente , Adulto , Carga Bacteriana , Biomarcadores , Fibrose Cística/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Escarro/química , Adulto Jovem
11.
Nutrients ; 13(10)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34684647

RESUMO

BACKGROUND: Long-term parenteral nutrition (PN) has been associated with renal complications, including hypercalciuria, nephrocalcinosis, proteinuria and reduced glomerular filtration rate (GFR). Pediatric data are scarce and mostly short-term. Our study aimed to evaluate renal complications in children with intestinal failure (IF) receiving long-term PN. METHODS: A cross-sectional study was performed in a tertiary pediatric IF clinic of patients receiving home-PN treatment for more than 1 year. Data regarding medical background, anthropometrics, laboratory investigations and abdominal sonography were retrieved. RESULTS: Complete data were available for 15 children (67% males), with a median age of 6 (range 1.5-15) years and a median (IQR) PN duration of 4 (1.5-6) years. Low-grade proteinuria was identified in 61% and microalbuminuria in 30% of the cohort. Hypercalciuria and hyperoxaluria were present in 50% and 46%, respectively. One patient had nephrocalcinosis. The estimated GFR was normal in all but one patient who had pre-existing kidney disease. CONCLUSIONS: Pediatric IF patients can present with preserved kidney function after years of PN treatment. Despite the high prevalence of hypercalciuria, nephrocalcinosis was not common. Base line and long-term monitoring of various aspects of renal function would be essential to characterize the effects of prolonged PN on kidney functions in pediatric patients.


Assuntos
Intestinos/fisiopatologia , Rim/fisiopatologia , Nutrição Parenteral Total , Adolescente , Aminoácidos/metabolismo , Criança , Pré-Escolar , Creatinina/urina , Feminino , Humanos , Lactente , Masculino , Proteinúria/complicações , Proteinúria/urina
12.
Nutrients ; 13(10)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34684650

RESUMO

The brain is approximately 75% water. Therefore, insufficient water intake may affect the cognitive performance of humans. The present study aimed to investigate the effects of water restriction and supplementation on cognitive performances and mood, and the optimum amount of water to alleviate the detrimental effects of dehydration, among young adults. A randomized controlled trial was conducted with 76 young, healthy adults aged 18-23 years old from Baoding, China. After fasting overnight for 12 h, at 8:00 a.m. of day 2, the osmolality of the first morning urine and blood, cognitive performance, and mood were measured as a baseline test. After water restriction for 24 h, at 8:00 a.m. of day 3, the same indexes were measured as a dehydration test. Participants were randomly assigned into four groups: water supplementation group (WS group) 1, 2, or 3 (given 1000, 500, or 200 mL purified water), and the no water supplementation group (NW group). Furthermore, participants were instructed to drink all the water within 10 min. Ninety minutes later, the same measurements were performed as a rehydration test. Compared with the baseline test, participants were all in dehydration and their scores on the portrait memory test, vigor, and self-esteem decreased (34 vs. 27, p < 0.001; 11.8 vs. 9.2, p < 0.001; 7.8 vs. 6.4, p < 0.001). Fatigue and TMD (total mood disturbance) increased (3.6 vs. 4.8, p = 0.004; 95.7 vs. 101.8, p < 0.001) in the dehydration test. Significant interactions between time and volume were found in hydration status, fatigue, vigor, TMD, symbol search test, and operation span test (F = 6.302, p = 0.001; F = 3.118, p = 0.029; F = 2.849, p = 0.043; F = 2.859, p = 0.043; F = 3.463, p = 0.021) when comparing the rehydration and dehydration test. Furthermore, the hydration status was better in WS group 1 compared to WS group 2; the fatigue and TMD scores decreased, and the symbol search test and operation span test scores increased, only in WS group 1 and WS group 2 (p < 0.05). There was no significant difference between them (p > 0.05). Dehydration impaired episodic memory and mood. Water supplementation improved processing speed, working memory, and mood, and 1000 mL was the optimum volume.


Assuntos
Afeto/fisiologia , Cognição/fisiologia , Suplementos Nutricionais , Água/farmacologia , Biomarcadores/sangue , Biomarcadores/urina , China , Desidratação/fisiopatologia , Comportamento de Ingestão de Líquido , Feminino , Hidratação , Humanos , Umidade , Masculino , Temperatura , Sede/fisiologia , Adulto Jovem
13.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684456

RESUMO

Mixed evidence was published regarding the association of sodium, potassium and sodium-to-potassium ratio (Na/K ratio) with renal function impairment. This study was conducted to further explore the relationship between sodium, potassium, NA/K ratio and kidney function in the general adult Chinese population. We performed a cross-sectional analysis using the baseline data from the Action on Salt China (ASC) study. 5185 eligible general adult participants from the baseline investigation of the ASC study were included in this analysis. Sodium, potassium and albumin excretion were examined from 24-h urine collection. Albuminuria was defined as albumin excretion rate (AER) greater than or equal to 30 mg/24-h. Mixed linear regression models, adjusted for confounders, were fitted to analyze the association between sodium, potassium and Na/K ratio, and natural log transformed AER. Mixed effects logistic regression models were performed to analyze the odds ratio of albuminuria at each quintile of sodium, potassium and Na/K ratio. The mean age of the participants was 49.5 ± 12.8 years, and 48.2% were male. The proportion of albuminuria was 7.5%.The adjusted mixed linear models indicated that sodium and Na/K ratio was positively associated with natural log transformed AER (Sodium: ß = 0.069, 95%CI [0.050, 0.087], p < 0.001; Na/K ratio: ß = 0.026, 95%CI [0.012, 0.040], p < 0.001). Mixed effects logistic regression models showed that the odds of albuminuria significantly increased with the quintiles of sodium (p < 0.001) and Na/K ratio (p = 0.001). No significant association was found between potassium and the outcome indicators. Higher sodium intake and higher Na/K ratio are associated with early renal function impairment, while potassium intake was not associated with kidney function measured by albumin excretion.


Assuntos
Albuminúria/epidemiologia , Albuminúria/etiologia , Albuminúria/metabolismo , Suscetibilidade a Doenças , Potássio/metabolismo , Sódio/metabolismo , Adulto , Albuminúria/urina , Biomarcadores , China/epidemiologia , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Cloreto de Sódio na Dieta
14.
Clin Lab ; 67(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655203

RESUMO

BACKGROUND: Lupus nephritis was established as the major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. This severity could be monitored by laboratory prognosis with accuracy and specificity for the disease. Recently, various SLE laboratory investigations still have had improper prognosis and also possibly causing tissue injury in the patients. The present study thus aimed to systematically explore a novel urinary protein for further development into a prognosis biomarker in patients. METHODS: Several urinary proteins that previously were reported with abnormal expression in SLE patients between 2014 - 2019 were comprehensively collected. These proteins were also analyzed for functional category and sites of expression using STIRNG, FUNRICH, and Uniport database. Thereafter, the level of altered protein candidate was then validated by western blotting, correlation analysis, and diagnostic performance. RESULTS: Vascular cell adhesion molecule-1 (VCAM1) protein was found in higher levels and also specific in SLE patients with nephritis. Moreover, VCAM1 has a role in immune response, inflammation, is expressed on plasma membrane of renal cells, and has the ability to secret into urine. The level of VCAM1 in urine of SLE patients was significantly higher than in healthy controls. The area under ROC curve (AUC) was also 0.891. Furthermore, the level of VCAM1 was dramatically associated with the severity of renal insufficiency (r = 0.738). CONCLUSIONS: VCAM1 may be a novel urinary biomarker for reliable prognosis of nephritis severity in SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Molécula 1 de Adesão de Célula Vascular/urina , Biomarcadores/urina , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Prognóstico
15.
Lancet Diabetes Endocrinol ; 9(11): 755-766, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34619106

RESUMO

BACKGROUND: Reductions in albuminuria are associated with a subsequent lower risk of kidney failure in patients with chronic kidney disease. The SGLT2 inhibitor dapagliflozin significantly reduced albuminuria in patients with type 2 diabetes and normal or near-normal kidney function. Whether this effect persists in patients with chronic kidney disease with and without type 2 diabetes is unknown. We assessed the effects of dapagliflozin on albuminuria in patients with chronic kidney disease with and without type 2 diabetes in the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial. METHODS: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 sites in 21 countries. Patients were eligible for the trial if they had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) between 25 mL/min per 1·73 m2 and 75 mL/min per 1·73 m2 and a urinary albumin-to-creatinine ratio (UACR) between 200 mg/g and 5000 mg/g (22·6 to 565·6 mg/mmol). Participants were randomly assigned to dapagliflozin 10 mg (AstraZeneca; Gothenburg, Sweden) once daily or matching placebo, in accordance with the sequestered, fixed randomisation schedule, using balanced blocks to ensure an approximate 1:1 ratio. Change in albuminuria was a pre-specified exploratory outcome of DAPA-CKD. Regression in UACR stage, defined as a transition from macroalbuminuria (≥300 mg/g) to microalbuminuria or normoalbuminuria (<300 mg/g), and progression in UACR stage, defined as a transition from less than 3000 mg/g to 3000 mg/g or greater, were additional discrete endpoints. The trial is registered with ClinicalTrials.gov, NCT03036150. FINDINGS: Between Feb 2, 2017, and April 3, 2020, 4304 patients were recruited and randomly assigned to either dapagliflozin (n=2152) or placebo (n=2152). Median UACR was 949 mg/g (IQR 477 to 1885). Overall, compared with placebo, dapagliflozin reduced geometric mean UACR by 29·3% (95% CI -33·1 to -25·2; p<0·0001); relative to placebo, treatment with dapagliflozin resulted in a geometric mean percentage change of -35·1% (95% CI -39·4 to -30·6; p<0·0001) in patients with type 2 diabetes and -14·8% (-22·9 to -5·9; p=0·0016) in patients without type 2 diabetes over the follow-up visits (pinteraction<0·0001) Among 3860 patients with UACR of 300 mg/g or greater at baseline, dapagliflozin increased the likelihood of regression in UACR stage (hazard ratio 1·81, 95% CI 1·60 to 2·05). Among 3820 patients with UACR less than 3000 mg/g at baseline, dapagliflozin decreased the risk of progression in UACR stage (0·41, 0·32 to 0·52). Larger reductions in UACR at day 14 during dapagliflozin treatment were significantly associated with attenuated eGFR decline during subsequent follow-up (ß per log unit UACR change -3·06, 95% CI -5·20 to -0·90; p=0·0056). INTERPRETATION: In patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin significantly reduced albuminuria, with a larger relative reduction in patients with type 2 diabetes. The similar effects of dapagliflozin on clinical outcomes in patients with or without type 2 diabetes, but different effects on UACR, suggest that part of the protective effect of dapagliflozin in patients with chronic kidney disease might be mediated through pathways unrelated to reduction in albuminuria. FUNDING: AstraZeneca.


Assuntos
Albuminúria/tratamento farmacológico , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/urina , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/urina , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Creatinina/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/urina , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Insuficiência Renal/prevenção & controle , Insuficiência Renal Crônica/tratamento farmacológico
16.
Front Immunol ; 12: 676105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650548

RESUMO

Background: Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Methods: Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Results: Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. Conclusions: This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/urina , Adulto , Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Proteína C-Reativa/análise , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/urina , Análise dos Mínimos Quadrados , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética
18.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638615

RESUMO

Metformin is the first-line antidiabetic drug that is widely used in the treatment of type 2 diabetes mellitus (T2DM). Even though the various therapeutic potential of metformin treatment has been reported, as well as the improvement of insulin sensitivity and glucose homeostasis, the mechanisms underlying those benefits are still not fully understood. In order to explain the beneficial effects on metformin treatment, various metabolomics analyses have been applied to investigate the metabolic alterations in response to metformin treatment, and significant systemic metabolome changes were observed in biofluid, tissues, and cells. In this review, we compare the latest metabolomic research including clinical trials, animal models, and in vitro studies comprehensively to understand the overall changes of metabolome on metformin treatment.


Assuntos
Hipoglicemiantes/farmacologia , Metaboloma/efeitos dos fármacos , Metformina/farmacologia , Animais , Biomarcadores/sangue , Biomarcadores/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemiantes/química , Resistência à Insulina , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica/métodos , Metformina/química
19.
Front Immunol ; 12: 676919, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594322

RESUMO

Introduction: Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN. Methods: One hundred IgAN patients with various proportions of crescents-24 with 1%-24%, 27 with 25%-49%, 21 with 50%-74% 12 with more than 75%, and 16 without crescents-were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry. Results: IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652-62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0-1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127-66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859-2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058-1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916-11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents. Conclusion: Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento/urina , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/patologia , Índice de Gravidade de Doença , Adulto , Biópsia , Feminino , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/urina , Humanos , Imuno-Histoquímica/métodos , Glomérulos Renais/patologia , Masculino , Lectina de Ligação a Manose/urina , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
20.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638835

RESUMO

Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers' profiling complications after kidney transplantation.


Assuntos
Vesículas Extracelulares/metabolismo , Rejeição de Enxerto/urina , Transplante de Rim , Rim/metabolismo , Aloenxertos , Biomarcadores/urina , Vesículas Extracelulares/imunologia , Rejeição de Enxerto/imunologia , Humanos , Rim/imunologia , Rim/cirurgia
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