RESUMO
Preeclampsia (PE), a pregnancy-related syndrome, has motivated extensive research to understand its pathophysiology and develop early diagnostic methods. 'Omic' technologies, focusing on genes, mRNA, proteins, and metabolites, have revolutionized biological system studies. Urine emerges as an ideal non-invasive specimen for omics analysis, offering accessibility, easy collection, and stability, making it valuable for identifying biomarkers. A comprehensive exploration of urinary omics in preeclampsia is discussed in this review. Proteomic studies identified biomarkers such as SERPINA-1 and uromodulin, showing promise for early diagnosis and severity assessment. Metabolomic analyses revealed alterations in metabolites like glycine and hippurate, providing insights into molecular mechanisms underlying PE. Challenges include methodological inconsistencies and the need for standardized protocols. Urinary omics technologies have significantly advanced our understanding of PE pathophysiology and hold promise for improved diagnosis and management. Biomarkers identified through these approaches offer potential for early detection, severity stratification, and elucidation of underlying mechanisms.
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Biomarcadores , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/urina , Pré-Eclâmpsia/metabolismo , Feminino , Biomarcadores/urina , Gravidez , Proteômica/métodos , Metabolômica/métodosRESUMO
PURPOSE OF REVIEW: This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. RECENT FINDINGS: Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. SUMMARY: Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.
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Biomarcadores , Ácido Cítrico , Rim Policístico Autossômico Dominante , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/fisiopatologia , Rim Policístico Autossômico Dominante/diagnóstico , Humanos , Animais , Ácido Cítrico/urina , Ácido Cítrico/uso terapêutico , Biomarcadores/urina , Taxa de Filtração Glomerular/efeitos dos fármacos , Progressão da Doença , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Rim/patologiaRESUMO
OBJECTIVE: The expansion of human activities in northern Colombia has increased human-snake encounters, particularly with venomous Porthidium lansbergii lansbergii. Given the limited knowledge of systemic envenomation effects and previous studies focusing only on early murine symptoms, this investigation aimed to describe the time-course physiopathology of P. lansbergii lansbergii envenomation following intramuscular injection in vivo. METHODS: Venom was inoculated in the gastrocnemius muscles of Swiss Webster mice, and blood, urine, and tissue samples were taken at different times to evaluate lethality and biochemical markers of renal function and oxidative stress. RESULTS: This study reports the first intramuscular LD50 for P. lansbergii lansbergii venom at 24.83 mg/Kg. Administering 80% of this LD50 induced early signs of renal injury, evidenced by urinary biomarkers over 24â h. The antioxidant activity was found at low levels in kidney tissue throughout the evaluated time post-envenomation. Malondialdehyde activity increased at the earliest point, while proinflammatory activity increased later. Urine metabolomics revealed elevated taurine and allantoin in the envenomed groups. DISCUSSION: Compensatory mechanisms in response to oxidative stress and tissue damage induced by the venom were evident in the envenomed mice over the evaluated time. However, histological analysis revealed evidence of pro-inflammatory processes occurring only at early times. Metabolomic analyses of urine samples identified taurine as a potential early biomarker of elevated oxidative stress and protein and creatinine levels. CONCLUSIONS: P. lansbergii lansbergii venom induces alterations in murine renal tissue, affecting urinary biomarkers of kidney function within hours post-envenomation. Delayed proinflammatory effects may suggest an antioxidant imbalance in the envenomed mice, with unknown long-term effects. Further research on the role of oxidative stress and inflammation in renal structure and function following envenomation is necessary, emphasizing the need for prompt clinical management.
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Estresse Oxidativo , Mordeduras de Serpentes , Animais , Camundongos , Mordeduras de Serpentes/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Viperidae , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Masculino , Biomarcadores/urina , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Dose Letal MedianaRESUMO
BACKGROUND: Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination power to identify subjects who might ultimately recover kidney function. METHODS: We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73m2): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects required kidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30 mL/min/1.73m2 and time to recovery of kidney function with dialysis independence in those with initial KRT. RESULTS: Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30 mL/min/1.73m2. The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of the kidney function was faster and led to a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis, uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98), and a cutoff of 2.60 ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT, the cut-off of uEGF/Cr of 2.0 ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6 months. CONCLUSIONS: Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment.
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Biomarcadores , Fator de Crescimento Epidérmico , Taxa de Filtração Glomerular , Glomerulonefrite , Rim , Recuperação de Função Fisiológica , Humanos , Masculino , Biomarcadores/urina , Feminino , Pessoa de Meia-Idade , Adulto , Fator de Crescimento Epidérmico/urina , Glomerulonefrite/urina , Glomerulonefrite/fisiopatologia , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Rim/fisiopatologia , Prognóstico , Índice de Gravidade de Doença , Idoso , Nefrite Lúpica/urina , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/fisiopatologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Creatinina/urina , Valor Preditivo dos Testes , Fatores de Tempo , Terapia de Substituição RenalRESUMO
Higher serum cortisol levels appear to be associated with stress that can overlap or manifest anxiety, fatigue, depression, and sleep dysfunction. These are common and intrusive non-motor symptoms of Parkinson's disease (PD). Thus, stress has been proposed to mediate Parkinson's disease development, and cortisol has been suggested as a biomarker for the generation of stress-related symptoms in Parkinson's disease. This study describes sensitive and robust disposable pipette extraction (DPX) and ultra-efficient liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to determine cortisol and cortisone (as potential endocrine biomarkers for Parkinson's disease) in 24-h urine and saliva samples obtained from Parkinson's disease patients. Important parameters on DPX extraction were optimized to achieve the best extraction recovery and cleanup efficiency. The proposed method was linear from 0.5 (lower limit of quantification) to 500 ng mL-1 for cortisol and from 3.0 (lower limit of quantification) to 500 ng mL-1 for cortisone. To determine whether urinary cortisol and urinary cortisone are adequate as biomarkers to evaluate the level of anxiety in patients suffering from Parkinson's disease, twenty-nine Parkinson's disease patients (18 with anxiety and 11 without anxiety) were selected for urine analysis. Based on the obtained results, 24-h urine samples obtained from Parkinson's disease patients with anxiety had higher cortisone levels than samples obtained from healthy controls. Receiving operating curves (ROC) analysis, which presented the area under the ROC curve (AUC = 0.733), showed that urinary cortisone levels (µg/24-h urine) were sensitive (56.3%) and specific (93.3%) for distinguishing Parkinson's disease patients with anxiety from healthy controls. In terms of salivary results, PD patients' samples taken 30 min after waking up had higher cortisol and cortisone levels than healthy controls, while their samples taken at night had lower cortisol and cortisone levels.
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Cortisona , Hidrocortisona , Doença de Parkinson , Saliva , Espectrometria de Massas em Tandem , Humanos , Doença de Parkinson/urina , Saliva/química , Cortisona/urina , Cortisona/análise , Espectrometria de Massas em Tandem/métodos , Hidrocortisona/urina , Hidrocortisona/análise , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Biomarcadores/urina , Limite de DetecçãoRESUMO
Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.
[Box: see text].
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Biomarcadores , Cistatina C , Recém-Nascido Prematuro , Tempo de Internação , Lipocalina-2 , Sepse , Humanos , Recém-Nascido , Cistatina C/sangue , Cistatina C/urina , Lipocalina-2/urina , Lipocalina-2/sangue , Biomarcadores/urina , Biomarcadores/sangue , Sepse/urina , Sepse/diagnóstico , Sepse/sangue , Masculino , Feminino , Recém-Nascido Prematuro/urina , Proteínas de Fase Aguda/urina , Proteínas Proto-Oncogênicas/urina , Proteínas Proto-Oncogênicas/sangueRESUMO
BACKGROUND: Two-thirds of patients with immunoglobulin light chain (AL) amyloidosis have renal involvement. The biochemical profile of kidney damage is poorly described. METHODS: A cross-sectional study was conducted involving patients diagnosed with AL amyloidosis and renal involvement between January 1, 2010, and April 30, 2022 at the Hospital Italiano de Buenos Aires. Participants were retrospectively identified from the Institutional Amyloidosis Registry. Patients diagnosed with AL amyloidosis and evidence of renal involvement were included. Individuals with other types of amyloidosis were excluded. The selection process involved a thorough review of medical records and registry data to ensure accurate identification and inclusion of eligible participants. RESULTS: Seventy-seven patients were included. At diagnosis, 90% of the subjects had proteinuria, with a median of 4.3 g/24 h, 61% had renal failure, and 47% presented nephrotic syndrome. Semi-automated urinary electrophoresis revealed 55% with non-selective and 21% with moderately selective glomerular proteinuria. Urine immunofixation indicated 64% with lambda monoclonal free light chains and 12% with kappa. Serum immunofixation demonstrated 48% with lambda monoclonal type and 25% with lambda IgG. At the time of diagnosis of AL amyloidosis, the median age was 66 years (IQR 53-72) and 49% were men. In addition to kidney involvement, other organs were also affected: heart in 53%, gastrointestinal system in 19%, peripheral nervous system in 16%, and liver in 16% of patients. CONCLUSION: Our study provides a biochemical profile in renal amyloidosis due to immunoglobulin light chains in a Latin American population. Proteinuria emerged as the most common finding in this cohort with frequent multiorgan involvement.
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Amiloidose de Cadeia Leve de Imunoglobulina , Nefropatias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Estudos Retrospectivos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/epidemiologia , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/urina , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Argentina/epidemiologia , Proteinúria/etiologia , Biomarcadores/sangue , Biomarcadores/urina , Síndrome Nefrótica/urina , Sistema de Registros , Cadeias lambda de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/urina , Cadeias kappa de Imunoglobulina/análise , Amiloidose/epidemiologia , Amiloidose/diagnósticoRESUMO
BACKGROUND: Renal dysfunction is a common complication following liver transplantation (LT). This study aimed to determine whether a comprehensive assessment of kidney function using nineteen serum and urinary biomarkers (BMs) within the first 48 h post-LT could enhance the prediction of severe acute kidney injury (AKI) and the need of kidney replacement therapy (KRT) during the first postoperative week. METHODS: Blood and urine (U) samples were collected during the pre- and postoperative periods. Nineteen BMs were evaluated to assess kidney health in the first 48 h after LT. Classification and regression tree (CART) cross-validation identified key predictors to determine the best BM combination for predicting outcomes. RESULTS: Among 100 LT patients, 36 developed severe AKI, and 34 required KRT within the first postoperative week. Preoperative assessment of U neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP) predicted the need for KRT with 75% accuracy. The combined assessment of U osmolality (OSM), U kidney injury molecule 1 (KIM-1), and tissue inhibitor of metalloproteinase (TIMP-1) within 48 h post-LT predicted severe AKI with 80% accuracy. U-OSM alone, measured within 48 h post-LT, had an accuracy of 83% for predicting KRT need, outperforming any BM combination. CONCLUSIONS: Combined BM analysis can accurately predict severe AKI and KRT needs in the perioperative period of LT. U-OSM alone proved to be an effective tool for monitoring the risk of severe AKI, available in most centers. Further studies are needed to assess its impact on AKI progression postoperatively.Registered at Clinical Trials (clinicaltrials.gov) in March 24th, 2014 by title 'Acute Kidney Injury Biomarkers: Diagnosis and Application in Pre-operative Period of Liver Transplantation (AKIB)' and identifier NCT02095431.
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Injúria Renal Aguda , Biomarcadores , Lipocalina-2 , Transplante de Fígado , Terapia de Substituição Renal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Injúria Renal Aguda/sangue , Injúria Renal Aguda/terapia , Biomarcadores/sangue , Biomarcadores/urina , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Receptor Celular 1 do Vírus da Hepatite A/sangue , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Lipocalina-2/urina , Lipocalina-2/sangue , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
INTRODUCTION: In soccer, most studies evaluate metabolic profile changes in male athletes, often using data from a single match. Given the current landscape of women's soccer and the effects of biological sex on the physiological response and adaptation to exercise, more studies targeting female athletes and analyzing pre- and post-game moments throughout the season are necessary. OBJECTIVES: To describe the metabolomics profile of female soccer athletes from an elite team in Brazil. The study observed the separation of groups in three pre- and post-game moments and identified the discriminating metabolites. METHODS: The study included 14 female soccer athletes. Urine samples were collected and analyzed using Nuclear Magnetic Resonance in pre-game and immediate post-game moments over three national championship games. The metabolomics data were then used to generate OPLS-DA and VIP plots. RESULTS: Forty-three metabolites were identified in the samples. OPLS-DA analyses demonstrated a progressive separation between pre-post conditions, as supported by an increasing Q2 value (0.534, 0.625, and 0.899 for games 1, 2 and 3, respectively) and the first component value (20.2% and 19.1% in games 1 and 2 vs. 29.9% in game 3). Eight out of the fifteen most discriminating metabolites appeared consistently across the three games: glycine, formate, citrate, 3-hydroxyvalerate, glycolic acid, trimethylamine, urea, and dimethylglycine. CONCLUSION: The main difference between the three games was the increasing separation between groups throughout the championship. Since the higher VIP-scores metabolites are linked to energy and protein metabolism, this separation may be attributed several factors, one being the accumulation of fatigue.
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Atletas , Biomarcadores , Metabolômica , Futebol , Futebol/fisiologia , Humanos , Metabolômica/métodos , Biomarcadores/urina , Feminino , Adulto Jovem , Metaboloma , Adulto , Brasil , Espectroscopia de Ressonância Magnética/métodosRESUMO
INTRODUCTION: Food intake biomarkers are used to estimate dietary exposure; however, selecting a single biomarker to evaluate a specific dietary component is difficult due to the overlap of diverse compounds from different foods. Therefore, combining two or more biomarkers can increase the sensitivity and specificity of food intake estimates. OBJECTIVE: This study aimed to evaluate the ability of metabolite panels to distinguish between self-reported fruit consumers and non-consumers among participants in the Longitudinal Study of Adult Health. MATERIALS AND METHODS: A total of 93 healthy adults of both sexes were selected from the Longitudinal Study of Adult Health. A 24-h dietary recall was obtained using the computer-assisted 24-h food recall GloboDiet software, and 24-h urine samples were collected from each participant. Metabolites were identified in urine using liquid chromatography coupled with high-resolution mass spectrometry by comparing their exact mass and fragmentation patterns using free-access databases. Multivariate receiver operating characteristic curve (ROC) analysis and partial least squares discriminant analysis were used to verify the ability of the metabolite combination to classify daily and non-daily fruit consumers. Fruit intake was identified using a 24 h dietary recall (24 h-DR). RESULTS: Bananas, grapes, and oranges are included in the summary. The panel of biomarkers exhibited an area under the curve (AUC) > 0.6 (Orange AUC = 0.665; Grape AUC = 0.622; Bananas AUC = 0.602; All fruits AUC = 0.679; Citrus AUC = 0.693) and variable importance projection score > 1.0, and these were useful for assessing the sensitivity and predictability of food intake in our population. CONCLUSION: A panel of metabolites was able to classify self-reported fruit consumers with strong predictive power and high specificity and sensitivity values except for banana and total fruit intake.
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Biomarcadores , Frutas , Metabolômica , Humanos , Feminino , Masculino , Biomarcadores/urina , Frutas/metabolismo , Frutas/química , Metabolômica/métodos , Pessoa de Meia-Idade , Adulto , Estudos Longitudinais , Brasil , Dieta , Idoso , Cromatografia Líquida/métodosRESUMO
Development of efficient portable sensors for accurately detecting biomarkers is crucial for early disease diagnosis, yet remains a significant challenge. To address this need, we introduce the enhanced luminescence lateral-flow assay, which leverages highly luminescent upconverting nanoparticles (UCNPs) alongside a portable reader and a smartphone app. The sensor's efficiency and versatility were shown for kidney health monitoring as a proof of concept. We engineered Er3+- and Tm3+-doped UCNPs coated with multiple layers, including an undoped inert matrix shell, a mesoporous silica shell, and an outer layer of gold (UCNP@mSiO2@Au). These coatings synergistically enhance emission by over 40-fold and facilitate biomolecule conjugation, rendering UCNP@mSiO2@Au easy to use and suitable for a broad range of bioapplications. Employing these optimized nanoparticles in lateral-flow assays, we successfully detected two acute kidney injury-related biomarkersâkidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)âin urine samples. Using our sensor platform, KIM-1 and NGAL can be accurately detected and quantified within the range of 0.1 to 20 ng/mL, boasting impressively low limits of detection at 0.28 and 0.23 ng/mL, respectively. Validating our approach, we analyzed clinical urine samples, achieving biomarker concentrations that closely correlated with results obtained via ELISA. Importantly, our system enables biomarker quantification in less than 15 min, underscoring the performance of our novel UCNP-based approach and its potential as reliable, rapid, and user-friendly diagnostics.
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Biomarcadores , Ouro , Receptor Celular 1 do Vírus da Hepatite A , Lipocalina-2 , Nanopartículas , Humanos , Biomarcadores/urina , Lipocalina-2/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Ouro/química , Nanopartículas/química , Érbio/química , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Dióxido de Silício/química , Túlio/química , Medições Luminescentes/métodos , Luminescência , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Limite de DetecçãoRESUMO
INTRODUCTION: Sjögren's disease (SD) is an immune-mediated chronic inflammatory disease that affects epithelial tissues, mainly salivary and lacrimal glands. It also presents extraglandular manifestations. The main renal manifestation is tubulointerstitial nephritis (TIN), which can manifest as renal tubular acidosis (RTA). Urinary citrate may be a biomarker of RTA in these patients. The objective of this study was to evaluate whether hypocitraturia is a predictive biomarker of RTA in a sample of patients with SD in a tertiary hospital in southern Brazil. METHODS: All patients with SD who met the inclusion criteria and who participated in the rheumatology outpatient clinic of the Irmandade Santa Casa de Misericórdia de Porto Alegre were included. Demographic, SD, serological and urinary data were obtained. RTA was considered in those patients who persistently presented urinary pH above 5.5 and serum pH below 7.35. Patients who persistently had urinary pH above 5.5 underwent a urinary acidification test with furosemide and fludrocortisone. These patients received 1 mg of fludrocortisone and 40 mg of furosemide and had their urine samples tested 2, 4 and 6 h after taking the medications. The test was stopped at any urine sample with pH 5.5 or less. The variables were expressed as mean and standard deviation or interquartile range. The association between hypocitraturia and RTA was assessed using the chi-square. RESULTS: Forty-two patients were included, 95.2% female with a median age of 61.73 years. The prevalence of complete distal RTA was 4.88%. Twenty-eight patients underwent urine acidification testing. Five patients had hypocitraturia, and two of them had complete distal RTA. The association between hypocitraturia and RTA was statistically significant (p < 0.012), with a sensitivity of 100%, specificity of 91.2% and accuracy of 91.7%. The negative predictive value was 100%. The global renal assessment of the population demonstrated two patients with RTA, one patient with decreased renal function and six patients with proteinuria greater than 0.5 g/24 h. CONCLUSION: The prevalence of RTA in the studied population was 4.88%. Hypocitraturia had high sensitivity and accuracy for the diagnosis of RTA.
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Acidose Tubular Renal , Biomarcadores , Ácido Cítrico , Furosemida , Síndrome de Sjogren , Humanos , Acidose Tubular Renal/diagnóstico , Acidose Tubular Renal/urina , Acidose Tubular Renal/etiologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/urina , Síndrome de Sjogren/diagnóstico , Feminino , Biomarcadores/urina , Pessoa de Meia-Idade , Masculino , Furosemida/uso terapêutico , Furosemida/administração & dosagem , Ácido Cítrico/urina , Fludrocortisona/uso terapêutico , Adulto , Concentração de Íons de Hidrogênio , Idoso , BrasilRESUMO
Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.
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Injúria Renal Aguda , Biomarcadores , Ponte Cardiopulmonar , Proteínas de Ligação a Ácido Graxo , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/sangue , Ponte Cardiopulmonar/efeitos adversos , Proteínas de Ligação a Ácido Graxo/urina , Proteínas de Ligação a Ácido Graxo/sangue , Biomarcadores/urina , Criança , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/urina , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Pré-EscolarRESUMO
BACKGROUND: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. METHODS: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17ß-estradiol, and cortisol. We used general linear models to assess linear (ß = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (ß2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. RESULTS: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (ßboys = 5.88% [1.21%, 10.78%], ßgirls = 4.10% [-0.02%, 8.39%]), and cortisol (ßboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (ß2boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (ß2boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (ßboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (ßboys = 3.90% [1.28%, 6.58%]) were positively associated with 17ß-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. CONCLUSIONS: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17ß-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.
Assuntos
Biomarcadores , Inseticidas , Humanos , Adolescente , Feminino , Masculino , Equador , Inseticidas/urina , Inseticidas/sangue , Biomarcadores/urina , Biomarcadores/sangue , Criança , Hidrocortisona/urina , Desidroepiandrosterona/urina , Desidroepiandrosterona/sangue , Estradiol/sangue , Estradiol/urina , Agricultura , Acetilcolinesterase/sangue , Acetilcolinesterase/metabolismo , Testosterona/sangue , Testosterona/urina , Saliva/química , Malation/urinaRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune and multisystem disease with a high public health impact. Lupus nephritis (LN), commonly known as renal involvement in SLE, is associated with a poorer prognosis and increased rates of morbidity and mortality in patients with SLE. Identifying new urinary biomarkers that can be used for LN prognosis or diagnosis is essential and is part of current active research. In this study, we applied an untargeted metabolomics approach involving liquid and gas chromatography coupled with mass spectrometry to urine samples collected from 17 individuals with SLE and no kidney damage, 23 individuals with LN, and 10 clinically healthy controls (HCs) to identify differential metabolic profiles for SLE and LN. The data analysis revealed a differentially abundant metabolite expression profile for each study group, and those metabolites may act as potential differential biomarkers of SLE and LN. The differential metabolic pathways found between the LN and SLE patients with no kidney involvement included primary bile acid biosynthesis, branched-chain amino acid synthesis and degradation, pantothenate and coenzyme A biosynthesis, lysine degradation, and tryptophan metabolism. Receiver operating characteristic curve analysis revealed that monopalmitin, glycolic acid, and glutamic acid allowed for the differentiation of individuals with SLE and no kidney involvement and individuals with LN considering high confidence levels. While the results offer promise, it is important to recognize the significant influence of medications and other external factors on metabolomics studies. This impact has the potential to obscure differences in metabolic profiles, presenting a considerable challenge in the identification of disease biomarkers. Therefore, experimental validation should be conducted with a larger sample size to explore the diagnostic potential of the metabolites found as well as to examine how treatment and disease activity influence the identified chemical compounds. This will be crucial for refining the accuracy and effectiveness of using urine metabolomics for diagnosing and monitoring lupus and lupus nephritis.
Assuntos
Biomarcadores , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Metabolômica , Humanos , Feminino , Lúpus Eritematoso Sistêmico/urina , Lúpus Eritematoso Sistêmico/metabolismo , Adulto , Metabolômica/métodos , Biomarcadores/urina , Masculino , Colômbia , Nefrite Lúpica/urina , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/metabolismo , Metaboloma , Pessoa de Meia-Idade , Estudos de Coortes , Estudos de Casos e Controles , Cromatografia Gasosa-Espectrometria de Massas , Adulto JovemRESUMO
BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.
Assuntos
Biomarcadores , Exposição Ambiental , Oligoelementos , Humanos , Biomarcadores/urina , Biomarcadores/metabolismo , Criança , Masculino , Feminino , Oligoelementos/análise , Oligoelementos/urina , Exposição Ambiental/efeitos adversos , Estudos Transversais , Adolescente , Lipocalina-2/urina , Taxa de Filtração Glomerular , Cobre/urina , Cobre/análise , Selênio/urina , Selênio/análise , Nefropatias/induzido quimicamente , Nefropatias/urina , Nefropatias/metabolismo , Rim/metabolismo , Pré-Escolar , Níquel/urinaRESUMO
BACKGROUND: Studying biomarkers in children with temporomandibular disorders (TMD) such as epinephrine, norepinephrine, and dopamine may reveal factors like screen time or sleep loss that affect these biomarkers and predict TMD-related pain, offering new research opportunities. AIM: To determine the association between stress and catecholamines with myofascial pain and headache related to TMD in children. DESIGN: Sixty-six 9- to 11-year-old children assisting at the clinics of Pediatric Dentistry of Universidad CES participated in the study. Myofascial pain and headache attributed to TMD were determined according to the Diagnostic Criteria for TMD (DC/TMD) Axis I. Stress was evaluated with the Perceived Stress Scale-Children (PSS-C), and a 24-h urine sample was analyzed using liquid chromatography to assay catecholamines. Single and multiple regression analyses were performed. RESULTS: Children with a mean age of 10.3 years participated in the study. The mean score of stress was 29 ± 4. Perceived stress, dopamine, epinephrine, and norepinephrine were statistically significant predictors of myofascial pain and headache attributed to TMD in the single- and multiple variable logistic regression analyses. CONCLUSION: Stressful states and its biological biomarkers increase the probability of developing myofascial pain and headache attributed to TMD in children.
Assuntos
Biomarcadores , Catecolaminas , Cefaleia , Estresse Psicológico , Transtornos da Articulação Temporomandibular , Humanos , Criança , Feminino , Masculino , Transtornos da Articulação Temporomandibular/complicações , Estresse Psicológico/complicações , Biomarcadores/urina , Catecolaminas/urina , Norepinefrina/urina , Epinefrina/urina , Dopamina/urina , Medição da DorRESUMO
PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 âmL/min/1.73 âm2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.
Assuntos
Diabetes Mellitus , Taxa de Filtração Glomerular , Transplante de Rim , Proteínas WT1 , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteínas WT1/urina , Diabetes Mellitus/urina , Biomarcadores/urina , Biomarcadores/sangue , Aloenxertos , Prognóstico , Seguimentos , Hemoglobinas Glicadas/metabolismoRESUMO
BACKGROUND: Acute Gastrointestinal Injury (AGI) is associated with adverse clinical outcomes, including increased mortality. We aimed to investigate the potential of citrulline and intestinal fatty acid binding protein (I-FABP) as biomarkers for early AGI diagnosis and predicting outcomes in surgical patients. METHODS: Prospective cohort study involving patients who underwent non-cardiac surgeries and were admitted to Intensive Care Units. AGI diagnosis was based on specific criteria, and severity was categorised following established guidelines. Statistical analyses were performed to assess the diagnostic accuracy of the biomarkers and their association with outcomes, P significant when <0.05. RESULTS: AGI was identified in 40.3% of patients with varying severity. Mortality rates were significantly higher in the AGI group in the ICU (19.4% vs. 0%, p = 0.001) and hospital (22.6% vs. 2.17%, p = 0.003). Urinary I-FABP levels on days 3 and 7 showed reasonable and good accuracy for AGI diagnosis (AUC 0.732 and 0.813, respectively). Urinary I-FABP levels on days 2 and 3 accurately predict sepsis. Urinary citrulline levels on day one predicted mortality (AUC 0.87) furthermore urinary I-FABP levels on day 2 showed reasonable accuracy (sensitivity 83.3%, specificity 92.4%). CONCLUSION: Urinary I-FABP and citrulline levels are promising diagnostic and prognostic markers in ICU patients following non-cardiac surgeries.
Assuntos
Citrulina , Proteínas de Ligação a Ácido Graxo , Complicações Pós-Operatórias , Humanos , Biomarcadores/urina , Citrulina/urina , Proteínas de Ligação a Ácido Graxo/urina , Período Pós-Operatório , Estudos Prospectivos , Complicações Pós-Operatórias/urinaRESUMO
BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.