RESUMEN
BACKGROUND: Bladder cancer is one of the most common malignancies but the corresponding diagnostic methods are either invasive or limited in specificity and/or sensitivity. This study aimed to develop a urine-based methylation panel for bladder cancer detection by improving published panels and validate performance of the new panel with clinical samples. METHODS: Related researches were reviewed and 19 potential panels were selected. RRBS was performed on a cohort with 45 samples to reassess these panels and a new panel inherited best markers was developed. The new panel was applied with qMSP platform to 33 samples from the RRBS cohort and the results were compared to those of RRBS. Lastly, another larger cohort with 207 samples was used to validate new panel performance with qMSP. RESULTS: Three biomarkers (PCDH17, POU4F2 and PENK) were selected to construct a new panel P3. P3 panel achieved 100% specificity and 71% sensitivity with RRBS in corresponding cohort and then showed a better performance of 100% specificity and 84% sensitivity with qMSP platforms in a balanced cohort. When validated with 207-sample cohort, P3 with qMSP showed a performance of 97% specificity and 87% sensitivity which was modestly improved compared to the panels it derided from. CONCLUSIONS: Overall, the P3 panel achieved relatively high sensitivity and accuracy in bladder cancer detection.
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Metilación de ADN , Detección Precoz del Cáncer/métodos , Urinálisis/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico , Orina/química , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/orina , Cadherinas/orina , Encefalinas/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Precursores de Proteínas/orina , Sensibilidad y Especificidad , Factor de Transcripción Brn-3B/orinaRESUMEN
BACKGROUND: Plasma proadrenomedullin (proADM) is a promising biomarker to predict disease severity in community-acquired pneumonia (CAP). Urinary biomarkers offer advantages over blood, including ease of collection. We evaluated the association between urinary proADM and disease severity in pediatric CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years with CAP. Urinary proADM/creatinine (Cr) was calculated. Disease severity was defined as: mild (discharged home), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with supplemental oxygen and complicated pneumonia) and severe (eg, vasopressors and invasive ventilation). Outcomes were examined using logistic regression within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of the 427 children included, higher proADM/Cr was associated with increased odds of severe disease compared with nonsevere disease [suspected CAP, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.003, 1.04); radiographic CAP, OR 1.03 (95% CI 1.01, 1.06)] when adjusted for other covariates. ProADM/Cr had an area under the receiver operating characteristic curve of 0.56 (threshold 0.9 pmol/mg) to differentiate severe from nonsevere disease in suspected CAP and 0.65 in radiographic CAP (threshold 0.82 pmol/mg). Healthy controls had less proADM in their urine (median, 0.61 pmol/mg) compared with suspected (0.87 pmol/mg, P = 0.018) and radiographic (0.73 pmol/mg, P = 0.016) CAP. CONCLUSIONS: Urinary proADM/Cr ratio measured at the time of emergency department visit was statistically associated with the development of severe outcomes in children with CAP, with stronger discriminatory performance in radiographic disease.
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Adrenomedulina/orina , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/orina , Neumonía/diagnóstico , Neumonía/orina , Precursores de Proteínas/orina , Índice de Severidad de la Enfermedad , Adolescente , Biomarcadores/orina , Niño , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Pronóstico , Estudios Prospectivos , Curva ROCRESUMEN
The formation of urinary stone, urolithiasis, is one the oldest known disease affecting human throughout different civilizations and times. The exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding. A single theory cannot explain its formation; therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall's plaque theory. In addition, various factors and components are identified that play an important role in the formation of these urinary calculi. In this review, composition of kidney stones, its prevalence/incidence, explanation of pathophysiological mechanisms and role of various factors; urinary pH, uric acid, parathyroid hormone, citrate, oxalate, calcium and macromolecules; osteopontin, matrix Gla protein, kidney injury molecules, urinary prothrombin fragment-1, Tamm-Horsfall protein, inter-α-inhibitors, have been discussed in detail.
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Ácido Cítrico/orina , Hiperoxaluria/orina , Osteopontina/orina , Urolitiasis/epidemiología , Urolitiasis/orina , alfa-Globulinas/orina , Animales , Proteínas de Unión al Calcio/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Hipercalciuria/orina , Fragmentos de Péptidos/orina , Prevalencia , Factores Protectores , Precursores de Proteínas/orina , Protrombina/orina , Factores de Riesgo , Ácido Úrico/orina , Orina/química , Urolitiasis/metabolismo , Uromodulina/orina , Proteína Gla de la MatrizAsunto(s)
Lesión Renal Aguda/diagnóstico , Biomarcadores/análisis , Sistemas de Atención de Punto/tendencias , Lesión Renal Aguda/prevención & control , Biomarcadores/orina , Encefalinas/análisis , Encefalinas/orina , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/análisis , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Unidades de Cuidados Intensivos/organización & administración , Precursores de Proteínas/análisis , Precursores de Proteínas/orina , Inhibidor Tisular de Metaloproteinasa-2/análisis , Inhibidor Tisular de Metaloproteinasa-2/orinaRESUMEN
Increasing number of patients with clinically suspected venous thromboembolism is referred to radiological departments for definitive diagnosis. A simple assay to exclude the diagnosis and avoid radiological examinations is needed. We have reported correlations between D-dimer and prothrombin fragment 1 + 2 measured in plasma and urine. To further develop an analysis based on urine, more understanding of thrombin generation in these patients is needed. The aim of this study was to compare ex vivo thrombin generation with in vivo markers in plasma and urine in patients with and without venous thromboembolism. Urine and blood samples were collected from patients with suspected venous thromboembolism. Commercially available enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the samples for in vivo thrombin generation. The ex vivo thrombogram parameters were measured by the calibrated automated thrombogram assay. Venous thromboembolism was verified with compression ultrasound of the lower extremity deep veins or with computer tomography of the pulmonary arteries. Venous thromboembolism was diagnosed in 117 of 591 patients, and they had significantly higher levels of urine and plasma prothromin fragment 1 + 2, D-dimer, lag time, time to peak, and endogenous thrombin potential when adjusted for covariates. The pattern of ex vivo and in vivo thrombin generation in patients with suspected venous thromboembolism was comparable when adjusted for covariates. Prothrombin fragment 1 + 2 in plasma and urine reflects thrombin generation ex vivo in the same manner. This indicates that urine may be an alternative substrate to quantify a procoagulant state.
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Productos de Degradación de Fibrina-Fibrinógeno , Fragmentos de Péptidos/orina , Precursores de Proteínas , Protrombina/orina , Tromboembolia Venosa/sangre , Tromboembolia Venosa/orina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ensayo de Inmunoadsorción Enzimática , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/orina , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Precursores de Proteínas/orina , Tromboembolia Venosa/diagnósticoRESUMEN
OBJECTIVE: Diabetes insipidus (DI) and primary polydipsia (PP) are characterised by polyuria and polydipsia. It is crucial to differentiate between these two disorders since the treatment is different. The aim of this study was to evaluate the diagnostic value of the short and an extended variant of the water deprivation test (WDT) and of measuring urinary vasopressin (AVP) in patients with polyuria and polydipsia. DESIGN: A retrospective, single-centre study based on WDTs performed between 2004 and 2014 including 104 consecutive patients with the polyuria-polydipsia syndrome. During a strict water deprivation, weight, urinary osmolality, urinary vasopressin and specific gravity were collected until one of the following was reached: i) >3% weight reduction, ii) Urinary specific gravity >1.020 or, urinary osmolality >800 mOsm/L, iii) Intolerable adverse symptoms such as excessive thirst. RESULTS: Out of 104 patients (67 women, 37 men), 21 (20%) were diagnosed with DI and 83 (80%) with PP. The median (interquartile range; range) test duration was 14 hours (10-16; 3-36) in patients with DI and 18 hours (14-24; 7-48) in patients with PP (P=0.011). Of those diagnosed with PP, 22 (26%) did not reach urinary specific gravity >1.020 nor urine osmolality >800 mOsm/L. Urine AVP did not overlap between patients with PP and patients with central DI. CONCLUSIONS: The short WDT is of limited value in the diagnostic work-up of polydipsia and polyuria and a partial DI may have been missed in every fourth patient diagnosed with PP. Urinary AVP has excellent potential in discriminating PP from central DI.
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Diabetes Insípida/diagnóstico , Neurofisinas/orina , Polidipsia Psicogénica/diagnóstico , Polidipsia/diagnóstico , Poliuria/diagnóstico , Precursores de Proteínas/orina , Vasopresinas/orina , Privación de Agua/fisiología , Adulto , Diabetes Insípida/sangre , Diabetes Insípida/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polidipsia/sangre , Polidipsia/orina , Polidipsia Psicogénica/sangre , Polidipsia Psicogénica/orina , Poliuria/sangre , Poliuria/orina , Valor Predictivo de las Pruebas , Estudios Retrospectivos , SíndromeRESUMEN
BACKGROUND: Urosepsis, a severe form of sepsis requires immediate medical attention for prognosis. It is clinically diagnosed by estimating serum procalcitonin (PCT) levels along with time taking urine and blood cultures. We explored NMR based profiling, deriving metabolites that could potentially aid diagnosis. METHODS: The proton NMR of serum and urine samples of healthy control subjects (n=32) and urosepsis cases (n=35) based on PCT levels, were analyzed. Four clinically identified non-urosepsis cases with high PCT levels were also differentiated through principal component analysis (PCA) of the serum samples. RESULTS: Quantification of serum and urine through Discriminant Function Analysis (DFA) afforded 93.7% and 91.7% correct classification respectively, along with identification of malonate and urea as potential biomarkers for the disease in both urine and serum samples. The partial least square discriminant analysis (PLS-DA) showed an R(2) value of 0.97 in both biofluids with Q(2)=0.87 and 0.85 for serum and urine respectively. The training set of serum samples provided precise prediction of the test set in a small cohort through random re-sampling method, while in urine samples, the predictions were inconclusive. CONCLUSIONS: Our pilot study reveals that (1)H NMR of serum metabolic profiling in combination with PCT levels may provide a rapid method for differentiation of urosepsis.
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Calcitonina/sangre , Precursores de Proteínas/sangre , Sepsis/sangre , Sepsis/etiología , Infecciones Urinarias/complicaciones , Biomarcadores/sangre , Biomarcadores/orina , Calcitonina/orina , Péptido Relacionado con Gen de Calcitonina , Estudios de Casos y Controles , Diagnóstico Diferencial , Humanos , Espectroscopía de Resonancia Magnética , Proyectos Piloto , Precursores de Proteínas/orina , Sepsis/diagnóstico , Sepsis/orina , Factores de TiempoRESUMEN
Parents frequently bring their children to the Emergency Department (ED) because of the fever without apparent source (FWAS). To avoid possible complications, it is important to recognize serious bacterial infection (SBI) as early as possible. Various tests, including different clinical scores and scales, are used in the laboratory evaluation of patients. However, it is still impossible to predict the presence of SBI with complete certainty. Galetto-Lacour et al. developed and validated a risk index score, named Lab-score. Lab-score is based on the three predictive variables independently associated with SBI: procalcitonin (PCT), C-reactive protein (CRP), and urinary dipstick. The objective of this study was to assess the performance of the Lab-score in predicting SBI in well-appearing infants ≤ 180 days of age with FWAS, who presented to ED and were hospitalized with suspicion of having SBI. Based on this study findings, white blood cells count (WBC), CRP, PCT, and lab-score ≥ 3 were confirmed as useful biomarkers for differentiation between SBI and non-SBI. Also, receiver operating characteristic curve (ROC) analysis confirmed that all of them were useful for differentiation between SBI and non-SBI patients with the highest area under curve (AUC) calculated for the Lab-score. The results of this research confirmed its value, with calculated sensitivity of 67.7% and specificity of 98.6% in prediction of SBI in infants aged ≤ 180 days. Its value was even better in infants aged ≤ 90 days with sensitivity of 75% and specificity of 97.7%. In conclusion, we demonstrated the high value of lab-score in detecting SBI in infants under 6 months of age with FWAS.
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Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Proteína C-Reactiva/orina , Calcitonina/orina , Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/epidemiología , Precursores de Proteínas/orina , Infecciones Bacterianas/sangre , Péptido Relacionado con Gen de Calcitonina , Croacia/epidemiología , Diagnóstico Precoz , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Fiebre de Origen Desconocido/sangre , Hospitalización , Humanos , Lactante , Recién Nacido , Masculino , Admisión del Paciente/estadística & datos numéricos , Prevalencia , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-Reactive Protein (CRP) and Procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known. METHODS: We used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionitis. RESULTS: PCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers. CONCLUSIONS: In women with subclinical IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.
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Proteína C-Reactiva/análisis , Calcitonina/análisis , Corioamnionitis/diagnóstico , Interleucina-6/análisis , Precursores de Proteínas/análisis , Adulto , Amniocentesis , Líquido Amniótico/química , Líquido Amniótico/microbiología , Infecciones Asintomáticas , Biomarcadores/sangre , Biomarcadores/orina , Proteína C-Reactiva/orina , Calcitonina/sangre , Calcitonina/orina , Péptido Relacionado con Gen de Calcitonina , Corioamnionitis/microbiología , Femenino , Sangre Fetal/inmunología , Rotura Prematura de Membranas Fetales , Humanos , Recién Nacido , Interleucina-6/sangre , Interleucina-6/orina , Trabajo de Parto Prematuro , Placenta/patología , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Nacimiento Prematuro , Precursores de Proteínas/sangre , Precursores de Proteínas/orina , Síndrome de Respuesta Inflamatoria SistémicaRESUMEN
BACKGROUND: Endothelin 1 (ET-1) contributes to chronic kidney disease (CKD) development and progression, and endothelin receptor antagonists are being investigated as a novel therapy for CKD. The proET-1 peptides, endothelin-like domain peptide (ELDP) and C-terminal pro-ET-1 (CT-proET-1), are both potential biomarkers of CKD and response to therapy with endothelin antagonists. METHODS AND RESULTS: We assessed plasma and urine ELDP and plasma CT-proET-1 in CKD patients with minimal comorbidity. Next, in a randomized double-blind crossover study of 27 subjects with proteinuric CKD, we examined the effects of 6 weeks of treatment with placebo, sitaxentan (endothelin A antagonist), and nifedipine on these peptides alongside the primary end points of proteinuria, blood pressure, and arterial stiffness. Plasma ELDP and CT-proET-1 increased with CKD stage (both P<0.0001), correlating inversely with estimated glomerular filtration rate (both P<0.0001). Following intervention, placebo and nifedipine did not affect plasma and urine ELDP or plasma CT-proET-1. Sitaxentan increased both plasma ELDP and CT-proET-1 (baseline versus week 6±SEM: ELDP, 11.8±0.5 versus 13.4±0.6 fmol/mL; CT-proET-1, 20.5±1.2 versus 23.3±1.5 fmol/mL; both P<0.0001). Plasma ET-1 was unaffected by any treatment. Following sitaxentan, plasma ELDP and CT-proET-1 correlated negatively with 24-hour urinary sodium excretion. CONCLUSIONS: ELDP and CT-proET-1 increase in CKD and thus are potentially useful biomarkers of renal injury. Increases in response to endothelin A antagonism may reflect EDN1 upregulation, which may partly explain fluid retention with these agents. CLINICAL TRIAL REGISTRATION: URL: www.clinicalTrials.gov Unique identifier: NCT00810732.
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Antagonistas de los Receptores de la Endotelina A/uso terapéutico , Endotelina-1/sangre , Isoxazoles/uso terapéutico , Precursores de Proteínas/sangre , Receptor de Endotelina A/efectos de los fármacos , Insuficiencia Renal Crónica/tratamiento farmacológico , Tiofenos/uso terapéutico , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Endotelina-1/orina , Femenino , Humanos , Isoxazoles/efectos adversos , Masculino , Persona de Mediana Edad , Nifedipino/uso terapéutico , Precursores de Proteínas/orina , Proteinuria/sangre , Proteinuria/tratamiento farmacológico , Receptor de Endotelina A/metabolismo , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Escocia , Tiofenos/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Rigidez Vascular/efectos de los fármacosRESUMEN
PURPOSE: Oliguria is a common symptom in critically ill patients and puts patients in a high risk category for further worsening renal function (WRF). We performed this study to explore the predictive value of biomarkers to predict WRF in oliguric intensive care unit (ICU) patients. PATIENTS AND METHODS: Single-center prospective observational study. ICU patients were included when they presented a first episode of oliguria. Plasma and urine biomarkers were measured: plasma and urine neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL), urine α1-microglobulin, urine γ-glutamyl transferase, urine indices of tubular function, cystatin C, C terminal fragment of pro-arginine vasopressin (CT-ProAVP), and proadrenomedullin (MR-ProADM). RESULTS: One hundred eleven patients formed the cohort, of whom 41 [corrected] had worsening renal function. Simplified Acute Physiology Score (SAPS) II was 41 (31-51). WRF was associated with increased mortality (hazard ratio 8.65 [95 % confidence interval (CI) 3.0-24.9], p = 0.0002). pNGAL, MR-ProADM, and cystatin C had the best odds ratio and area under the receiver-operating characteristic curve (AUC-ROC: 0.83 [0.75-0.9], 0.82 [0.71-0.91], and 0.83 [0.74-0.90]), but not different from serum creatinine (Screat, 0.80 [0.70-0.88]). A clinical model that included age, sepsis, SAPS II, and Screat had AUC-ROC of 0.79 [0.69-0.87]; inclusion of pNGAL increased the AUC-ROC to 0.86 (p = 0.03). The category-free net reclassification index improved with pNGAL (total net reclassification index for events to higher risk 61 % and nonevents to lower 82 %). CONCLUSIONS: All episodes of oliguria do not carry the same risk. No biomarker further improved prediction of WRF compared with Screat in this selected cohort of patients at increased risk defined by oliguria.
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Oliguria/sangre , Oliguria/orina , Insuficiencia Renal/sangre , Insuficiencia Renal/orina , Proteínas de Fase Aguda/orina , Adrenomedulina/orina , Anciano , alfa-Globulinas/orina , Biomarcadores/sangre , Biomarcadores/orina , Cistatina C/orina , Progresión de la Enfermedad , Femenino , Glicopéptidos/orina , Humanos , Unidades de Cuidados Intensivos , Pruebas de Función Renal , Lipocalina 2 , Lipocalinas/sangre , Lipocalinas/orina , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Precursores de Proteínas/orina , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/orina , Insuficiencia Renal/terapia , gamma-Glutamiltransferasa/sangre , gamma-Glutamiltransferasa/orinaRESUMEN
BACKGROUND: Alveolar-capillary membrane leaks can increase the amount of surfactant protein B (SP-B) in the bloodstream. The purpose of this study was to measure the concentration of C-proSP-B, a SP-B precursor that includes C-terminal domains, in various body fluids of newborn infants and determine its dependence on gestational age. METHODS: C-pro-SPB was measured in amniotic fluid and umbilical cord blood at birth, and in peripheral blood and urine on postnatal day 3 in 137 newborn infants with a median birth weight of 2015 g (range, 550-4475 g) and gestational age of 34 weeks (range, 23-42 weeks). RESULTS: C-proSP-B levels differed more than 100-fold among samples. The levels (median; interquartile range) were highest in peripheral blood (655.6 ng/mL; 419.0-1467.0 ng/mL) and lowest in urine (3.08 ng/mL; 2.96-3.35 ng/mL). C-proSP-B levels in amniotic fluid (314.9 ng/mL; 192.7-603.6 ng/mL) were approximately half of those in peripheral blood. In cord blood C-proSP-B was slightly lower (589.1 ng/mL; 181.2-1129.0 ng/mL) compared with peripheral blood. C-proSP-B levels significantly increased in all the fluids sampled except urine with decreasing gestational age (p < 0.001). CONCLUSIONS: This novel assay allows for the quantitative measurement of C-proSP-B in blood and amniotic fluid. The dependence of C-proSP-B on gestational age may hamper its use for the detection of alveolar leaks in preterm newborns.
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Líquido Amniótico/química , Sangre Fetal/química , Edad Gestacional , Precursores de Proteínas/sangre , Proteolípidos/sangre , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Mediciones Luminiscentes , Masculino , Precursores de Proteínas/análisis , Precursores de Proteínas/orina , Proteolípidos/análisis , Proteolípidos/orina , Estadísticas no ParamétricasRESUMEN
BACKGROUND/AIMS: The effect of angiotensin-converting enzyme inhibition (ACEi) is amply documented in several pathological conditions. However, there are few reports about the effect of chronic ACEi on salt and water balance.The present work evaluates the effect of chronic ACEi on salt and water balance in a population of children receiving enalaprilchronically in order to reduce albuminuria elicited by auremic hemolytic syndrome. METHODS: Nine children aged from 9 to 19 years with normal glomerular filtration rate, normotension and with urinary concentration capacity preserved were treated with enalapril with doses ranging between 0.1 and 0.30 mg/kg/day. Diuresis, urinary absolute and fractional excretion of Na(+), K(+) and urea, creatinine clearance,osmolal clearance and tubular water reabsorption were measured under three experimental procedures: (1)with free access to water; (2) with a water load and (3) with water restriction. In the last group urinary antidiuretic hormone(ADH) was measured. These tests were performed ina paired way, just before starting ACEi treatment and after 6 months of enalapril treatment. RESULTS: Enalapril treatment diminished the urinary concentration capacity without affecting Na(+) and K(+) urinary excretion. Creatinine clearance was not modified except in the condition of water load where a fall in it was found after ACEi. ADH increased after enalapril treatment in children under water restriction. CONCLUSION: In these children chronic ACEi decreases urinary concentration capacity.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Riñón/efectos de los fármacos , Agua/metabolismo , Adolescente , Niño , Creatinina/sangre , Creatinina/orina , Femenino , Humanos , Riñón/metabolismo , Masculino , Neurofisinas/orina , Potasio/orina , Precursores de Proteínas/orina , Sodio/orina , Urea/sangre , Urea/orina , Vasopresinas/orinaRESUMEN
PURPOSE: To compare two first febrile urinary tract infection (UTI) management protocols with regards to the diagnosis of high-grade vesicoureteral reflux (VUR) and cost. METHODS: This study compared two cohorts of children under 16 years of age, admitted for a first episode of febrile UTI. The first group (in 2005) was managed according to previous recommendations (IV treatment and cystography performed for all children under 3 years of age). The second group (in 2006) was managed according to age and procalcitonin level. High-grade VUR frequency, UTI recurrence, hospitalization rate, and cost were compared between the two cohorts. RESULTS: A total of 225 children were included in 2005 and 116 in 2006. High-grade VUR was found in 6.2 and 9.5% of the patients in 2005 and 2006, respectively (P=0.274). There was no statistically significant difference in the UTI recurrence rate between the two cohorts (5.3% in 2005 and 8.6% in 2006; P=0.237). The mean cost of an episode of febrile UTI was not significantly different in 2005 and 2006 (2235 in 2005, 2256 in 2006; P=0.902), but was lower for children older than 6 months in 2006 (1292 versus 1882 in 2005; P=0.0042). CONCLUSION: Our management protocol for a first febrile UTI episode in children based on procalcitonin levels seems to be suitable for the diagnosis of high-grade VUR. The hospitalization rate and the mean cost of management for children older than 6 months of age was significantly reduced in 2006. The management guidelines for a first occurrence of febrile UTI in children should be reconsidered.
Asunto(s)
Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Reflujo Vesicoureteral/complicaciones , Reflujo Vesicoureteral/tratamiento farmacológico , Adolescente , Antibacterianos/uso terapéutico , Biomarcadores/orina , Calcitonina/orina , Péptido Relacionado con Gen de Calcitonina , Niño , Preescolar , Estudios de Cohortes , Femenino , Fiebre/microbiología , Francia , Humanos , Lactante , Pacientes Internos , Tiempo de Internación/economía , Masculino , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Precursores de Proteínas/orina , Sensibilidad y Especificidad , Resultado del Tratamiento , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/economía , Infecciones Urinarias/orina , Reflujo Vesicoureteral/diagnóstico , Reflujo Vesicoureteral/economía , Reflujo Vesicoureteral/orinaRESUMEN
BACKGROUND/AIMS: Prohepcidin and the active form hepcidin-25 are two variants of the peptide hormone hepcidin for iron homoeostasis. Their regulatory role and usefulness as biomarkers of the iron status are uncertain. Our aim is to describe the intra-individual variance of serum and urinary hepcidin-25 and prohepcidin concentrations, the mutual associations of the 4 hepcidin formats, and their correspondence with iron status variables in male Guatemalan volunteers. METHODS: Eight healthy adult males provided serial samples of serum and urine without previous iron dosing over 6 intervals during a 9-week protocol period. Prohepcidin was assayed by a commercial enzyme immunoassay, and hepcidin-25 species in serum and urine were analysed by time-of-flight mass spectrometry after prior enrichment procedures. RESULTS: Serum hepcidin-25 levels correlated significantly with urinary hepcidin-25 concentrations, whereas serum and urinary prohepcidin were not associated with one another or with the homologous or converse formats for hepcidin-25. Serum ferritin and transferrin saturation were significantly correlated with serum hepcidin-25 concentrations, but not with urine hepcidin-25 or with either format of prohepcidin. CONCLUSION: Hepcidin-25 shows correspondence across biological fluids, and the background 'status' of hepcidin activation may be related to the host's iron stores, whereas prohepcidin concentrations showed no promise in this regard.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/sangre , Péptidos Catiónicos Antimicrobianos/orina , Hierro/sangre , Estado Nutricional , Precursores de Proteínas/sangre , Precursores de Proteínas/orina , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Ferritinas/sangre , Guatemala , Hepcidinas , Humanos , Hierro/metabolismo , Deficiencias de Hierro , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores de Tiempo , Transferrina/análisis , Transferrina/metabolismo , Adulto JovenRESUMEN
UNLABELLED: Hepcidin is a small defensin-like peptide, the production of which by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Kidneys are involved in not only the synthesis of hepcidin, but they also may be involved in its elimination. A cross-sectional study was performed to assess prohepcidin and hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to type of renal replacement therapy and prohepcidin and hepcidin correlations with renal function, iron status, and markers of inflammation. METHODS: Prohepcidin and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using commercially available kits in 102 patients on hemodialyses, 17 on hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers. RESULTS: In hemodialyzed and peritoneally dialyzed patients with residual renal function, serum prohepcidin (264.21 +/- 95.84 vs. 341.84 +/- 90.45 ng/mL, p < 0.01; 142.76 +/- 57.87 vs. 238.42 +/- 84.32 ng/mL, p < 0.01, respectively) and hepcidin (178.89 +/- 89.87 vs. 295.76 +/- 129.65 ng/mL, p < 0.01; 108.43 +/- 75.49 vs. 186.53 +/- 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in anuric patients. In peritoneal effluent, prohepcidin level was significantly higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis, residual renal function, ferritin, and hsCRP were predictors of hepcidin in hemodialyzed patients, while residual renal function and ferritin were predictors of hepcidin in peritoneally dialyzed patients. CONCLUSIONS: Residual renal function seems to play a pivotal role in hepcidin levels in dialyzed patients. In addition, the presence of low-grade inflammation, more pronounced in anuric patients, and functional iron deficiency may also contribute to the elevated hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may partially explain its lower concentration in peritoneal dialysis and hemodiafiltration.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/sangre , Hemodiafiltración , Fallo Renal Crónico/terapia , Diálisis Peritoneal , Precursores de Proteínas/sangre , Adulto , Anciano , Péptidos Catiónicos Antimicrobianos/orina , Biomarcadores/sangre , Estudios Transversales , Hepcidinas , Humanos , Inflamación/sangre , Hierro/sangre , Fallo Renal Crónico/sangre , Fallo Renal Crónico/orina , Pruebas de Función Renal , Persona de Mediana Edad , Precursores de Proteínas/orinaRESUMEN
The intestine and kidney are linked by a mechanism that increases salt excretion in response to salt intake. The peptide uroguanylin (UGn) is thought to mediate this signaling axis. Therefore, it was surprising to find (as reported in a companion publication) that UGn is stored in the intestine and circulates in the plasma almost exclusively in the form of its biologically inactive propeptide precursor, prouroguanylin (proUGn), and, furthermore, that infused proUGn leads to natriuretic activity. Here, we investigate the fate of circulating proUGn. Kinetic studies show rapid renal clearance of radiolabeled propeptide. Radiolabel accumulates at high specific activity in kidney (relative to other organs) and urine (relative to plasma). The principal metabolites found in kidney homogenates are free cysteine and methionine. In contrast, urine contains cysteine, methionine, and three other radioactive peaks, one comigrating with authentic rat UGn15. Interestingly, proUGn is not converted to these or other metabolites in plasma, indicating that circulating proUGn is not processed before entering the kidney. Therefore, our findings suggest that proUGn is the true endocrine agent released in response to salt intake and that the response of the kidney is dependent on conversion of the propeptide to an active form after it reaches the renal tubules. Furthermore, proUGn metabolites (other than small amounts of cysteine and methionine) are not returned to the circulation from the kidney or any other organ. Thus, to respond to proUGn released from the gut, any target organ must use a local mechanism for production of active peptide.