Sodio urinario como factor pronóstico para mortalidad en pacientes con falla cardiaca aguda descompensada

Introducción. En los pacientes con falla cardíaca, el sodio urinario se ha propuesto como marcador de gravedad y resistencia a los diuréticos, pero los resultados de los estudios reportados son heterogéneos. Objetivo. Evaluar el sodio en orina ocasional como factor pronóstico de mortalidad en pacientes con falla cardiaca descompensada. Materiales y métodos. Se realizó un análisis anidado de casos y controles de una cohorte prospectiva de falla cardíaca descompensada. El desenlace primario fue mortalidad a los 180 días. Se hizo un análisis bivariado para evaluar las variables que se asocian con la mortalidad. Se analizaron las diferencias de las variables clínicas entre los grupos con sodio urinario mayor o menor de 70 mEq/L. Resultados. Se incluyeron 79 pacientes de los cuales 15 fallecieron a los 180 días. La edad promedio fue de 68,9 años (DE: ±13,8), 30 eran mujeres (38 %). Quince pacientes (18,9 %) tuvieron un sodio en orina inferior a 70 mEq/L. En el análisis bivariado se encontró una asociación significativa de la mortalidad con las hospitalizaciones, la presión arterial sistólica inferior a 90 mm Hg, el uso de inotrópicos y el sodio urinario inferior a 70 mEq/L. Los pacientes con sodio urinario bajo habían estado hospitalizados con mayor frecuencia en el último año, tenían menores valores de sodio sérico y presión arterial al ingreso. Conclusión. Los pacientes con sodio urinario inferior a 70 mEq/L tienen características de mayor gravedad. En el análisis bivariado, el sodio urinario se asoció con mortalidad a los 180 días.

Introduction. Urinary sodium has been proposed as a prognostic marker and indicator of the diuretic response in patients with heart failure. However, study results are heterogeneous. Objective. To evaluate the spot urinary sodium level as a risk factor for mortality in patients with decompensated heart failure. Materials and methods. We conducted a case-control study nested in a prospective cohort of patients with decompensated heart failure. The primary outcome was mortality at 180 days. The risk factors associated with mortality were evaluated through a bivariate analysis. Differences in clinical variables between groups with urinary sodium greater than or lesser than 70 mEq/L were analyzed. Results. The study included 79 patients; 15 died at 180 days. Their mean age was 68.9 years (SD=± 13.8); 30 were women (38%), and 15 (18.9%) had urinary sodium <70 mEq/L. In the bivariate analysis, a significant association was found between mortality and past medical history of hospitalizations, SBP<90 mm Hg, the use of inotropes, and urinary sodium <70 mEq/L. Regarding clinical characteristics, patients with low urinary sodium level in the last year were hospitalized more frequently with hyponatremia and hypotension at admission. Conclusion. Patients with urinary sodium <70 mEq/L had more severe signs. In a bivariate analysis, urinary sodium was associated with mortality at 180 days.

Nueva ecuación para la estimación de la natriuresis diaria a partir de parámetros en plasma y orina aislada en población chilena / A new equation to estimate daily natriuresis from parameters in plasma and spot urine sample in the Chilean population

Background: Excessive sodium intake is associated with increased cardiovascular morbidity and mortality. Daily sodium intake is usually inferred from sodium excretion in a 24-hour urine collection, which is cumbersome and prone to errors. Different formulas have attempted to estimate 24-hour urinary sodium from a spot urine sample. Unfortunately, their concordances are insufficient and have not been tested in our population. Aim: To develop an equation to predict 24-hour urine sodium from parameters in plasma and spot urine samples. To validate the equation and compare it with other formulas in Chilean population. Material and Methods: Analysis of 24-hour urine collections, plasma sample and spot urine sample from 174 adult outpatients (81% females) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. These were collected between 2015 and 2019 using standardized methods and educating patients about the correct method to collect 24 h urine samples. In all these patients, creatinine and electrolytes were measured in plasma and urine. A new equation was developed using a multiple linear regression model. Results: Twenty-four-hour urine sodium excretion was significantly correlated with age, weight, height, eGFR, plasma osmolarity, urine electrolytes and parameters obtained from spot urine sample, among others. The new equation had a linear correlation with 24-hour natriuresis of 0.91 and the concordance was 0.9. The predictive capacity of the new equation was better than the existing formulas. Conclusions: We developed a formula to accurately predict daily natriuresis in the Chilean population.

Relación entre la excreción urinaria de sodio, la presión arterial y el índice de masa corporal en adultos-jóvenes / Relationship between urinary sodium excretion, blood, pressure and BMI in young adults

Introducción: la excreción urinaria de sodio diaria (Natriuria) refleja en cierta medida el consumo de sal en la dieta y este ha sido relacionado ya desde la literatura anglosajona con la hipertensión arterial; y más recientemente con alteraciones metabólicas como el sobrepeso y la obesidad; por ende, se deduce que sería un determinante de relevancia en el estudio de las enfermedades cardio-cerebro-vasculares. Objetivos: determinar la relación entre la excreción urinaria de sodio, la presión arterial y el IMC en los adultos-jóvenes del Hospital Nacional de Itauguá. Material y métodos: estudio observacional descriptivo prospectivo con componentes analíticos realizado en adultos-jóvenes internados y personal de blanco del servicio de Clínica Médica del Hospital Nacional en 2018. Resultados: la edad media fue 35 ± 11 años. Predominaron pacientes del sexo femenino (62%). La incidencia de la hipertensión arterial fue del 66%, el sobrepeso se observó en un 40% y la obesidad en el 30%. La Natriuria promedio fue 8,8gr/día (DE: ±0,8 gr/día) que correspondería al contenido diario de sal en la dieta de los individuos estudiado y su correlación con las presiones arteriales tanto sistólicas (r=0,34) como diastólicas (r=0,34) y el IMC (r=0,60) arrojaron datos positivos con una p <0,01. Conclusión: el consumo de sal fue casi el doble del recomendado y varios ligeramente con el último informe realizado en nuestro país y con países vecinos. Se demostró una relación positiva entre el consumo de sal elevado con los parámetros clínicos expuestos, se vio igual correlación tanto para la presión sistólica como la diastólica y una mayor relación con el IMC presentándose una línea de tendencia que supone a mayor IMC mayor natriuria y consecuentemente mayor presión arterial.

Introduction: the daily urinary excretion of sodium (Natriuria) reflects the consumption of salt in the diet and this has been already related from the Anglo-Saxon literature with arterial hypertension; and more recently with metabolic alterations such as overweight and obesity; therefore it is deduced that it would be a relevance determinant in the study of cardic-brain-vascular diseases. Objectives: to determine the relationship between urinary sodium excretion, blood pressure and BMI in young adults of the "Hospital Nacional de Itauguá". Material and methods: prospective, descriptive, observational study with analytical components carried out in adults-young inpatients and staff of the Medical Clinic service of the "Hospital Nacional" in 2018. Results: the average age was 35 ± 11 years. Female patients predominated (62%). The incidence of arterial hypertension was 66%, overweight was observed in 40% and obesity in 30%. The average of Natriuria was 8.8gr /day (SD: ± 0.8 g / day) that would correspond to the daily salt content in the diet of the individuals studied and its correlation with both systolic blood pressures (r = 0.34) as diastolic (r = 0.34) and the BMI (r = 0.60) yielded positive data with p <0.01. Conclusion: the consumption of salt was almost double that recommended and varied slightly with the last report made in our country and with neighboring countries. A positive relationship between high salt intake and exposed clinical parameters was demonstrated, the same correlation was seen both for systolic and diastolic pressures and a higher relationship with BMI, presenting a trend line that supposes a higher BMI higher natriuria and consequently higher blood pressure.

Encuesta de ioduria como control de la ingesta de iodo / Survey on urinary iodine as iodine intake control / Pesquisa de iodúria como um controle da ingestão de iodo

Desde 1964, año en que se incorporó iodo a la sal de mesa, ha disminuido notoriamente el bocio endémico en Uruguay. Por haberse modificado con posteridad, en dos oportunidades la proporción del iodo en la misma, se tornó imprescindible reevaluar los niveles de la ingesta poblacional siguiendo las recomendaciones de la OMS. Los objetivos de este estudio fueron evaluar los niveles de iodo en la población a través de las iodurias, seleccionar la mejor forma de expresar su excreción y estudiar la relación de las mismas con el sodio urinario. Se analizaron 491 muestras de orina de niños en edad escolar, de nueve departamentos del Uruguay y se determinó iodo, sodio y creatinina. Se observó una mediana de 0,248 mg/L de iodo, valor adecuado según las recomendaciones de la OMS (0,100-0,300 mg/L), una distribución no paramétrica de la ioduria expresada como cociente de Iodo/ creatinina en mg/g que discrimina mejor los valores atípicos respecto de la expresión de iodurias en mg/L, una pobre relación entre la excreción de iodo y el sodio, (r2=0,199) lo que indica que su aporte no es exclusivo de la sal de mesa y un predominio de excreción más elevado en los niños de menor edad respecto de los mayores.

The presence of endemic goiter in Uruguay has decreased markedly since the addition of iodine to table salt in 1964. It was essential to evaluate the population levels of iodine intake accordingly to WHO specifications, since iodine support to the table salt has been modified twice. The aims of this study were to evaluate the levels of iodine in the population through the urinary iodine levels, select the best way to express their excretion and study the relationship thereof with urinary sodium. Four hundred ninety- one urine samples were analyzed from school children from nine states of Uruguay and sodium, creatinine and iodine were measured. The iodine median was 0.248 mg/L, an adequate value according to WHO specifications (0.100-0.300 mg/L). The expression of urinary iodine as the ratio between urinary iodine and urinary creatinine (mg/g) had a non-parametric distribution that discriminate the atypical values better than the urinary iodine (mg/L). The relationship between iodine excretion and sodium was poor (r2=0.199), indicating that the input of iodine does not come exclusively from table salt. Younger children had a greater excretion than older ones.

Desde 1964, quando o iodo foi adicionado ao sal de mesa, diminuiu acentuadamente o bócio endêmico no Uruguai. Por ter sido modificada posteriormente, em duas oportunidades, a proporção do iodo no mesmo, tornou-se essencial reavaliar os níveis de ingestão da população seguindo as recomendações da OMS. Os objetivos deste estudo foram avaliar os níveis de iodo na população através das iodúrias, selecionar a melhor maneira de expressar sua excreção e estudar a relação das mesmas com o sódio urinário. 491 amostras de urina de crianças em idade escolar, de nove departamentos do Uruguay foram analisadas, determinando-se iodo, sódio e creatinina. Foi observada uma mediana de 0.248 mg/L de iodo, valor apropriado de acordo com as recomendações da OMS (0.100-0.300 mg/L), também uma distribuição não paramétrica expressa como quociente de iodo/creatinina em mg/g que discrimina de uma maneira melhor os valores atípicos para a expressão de iodúrias em mg/L, uma pobre relação entre a excreção de iodo e de sódio, (r2=0,199 ), indicando que a sua contribuição não é exclusiva do sal de mesa e uma predominância de excreção maior nas crianças mais novas em relação às maiores.

Patrones de excreción urinaria de Sodio en población adulta en muestras de orina espontánea / Urinary sodium excretion patterns in adult population in spot urine samples

Introducción: El presente estudio describe los patrones de natriuresis según las características clínicas y sociodemográficas en una población adulta de Asunción. Métodos: Estudio transversal tipo encuesta y toma de muestra de orina a personas que acudieron al Mercado de Abasto y al Policlínico Municipal durante los meses de junio-setiembre del 2014. Se estimó natriuria en muestras de orina espontánea a primera hora de la mañana y en ayunas. Se incluyeron sujetos de 18 a 65 años. Se compararon las medianas de los valores de natriuria en mmol/L, utilizándose el test U de Mann-Whitney para comparar las variables de dos categorías y Kruskal-Wallis para las que tienen más de dos categorías. Resultados: Se aplicó la encuesta y se tomó muestra de orina a 463 personas. El 69,5% (322) eran mujeres. La media de edad fue 50,5 años (DE: 14,2). El 26,6% (123) negó antecedentes patológicos. La mediana de natriuria global fue 97,5 mmol/L (RIC: 59,3­139,3). Los niveles de natriuria no presentaron diferencias por sexo. Las personas menores de 30 años, con bajo consumo de verduras y mayor consumo de frituras presentaron valores de natriuria altos y estadísticamente significativos. El grupo de sujetos sanos mostró mayor excreción de sodio que los que refirieron diabetes o hipertensión arterial. Conclusiones: La mayor excreción de sodio en orina observada se presenta en personas jóvenes, sin antecedentes patológicos y, al mismo tiempo son los que también presentan los peores hábitos alimenticios. Estos resultados muestran la necesidad de intervención en el ámbito de la salud pública a fin de prevenir la patología cardiovascular y renal del futuro.

Introduction: The present study describes natriuresis patterns according to clinical and sociodemographic characteristics in adult population of Asuncion. Methods: Cross-sectional study of convenience sampling to people who attended the Mercado de Abasto and the Municipal Polyclinic during June to September 2014. People from 18 to 65 years old were included. Sodium was estimated from urine samples of spot urine taken in the morning and fasting. Median values of natriuresis in mmol/L were compared using the test Mann-Whitney and Kruskal-Wallis. Results: 463 people participated. 69.5% (322) were women. The mean age was 50.5 years (SD 14.2). 26.6% (123) denied pathological medical history. The median overall natriuresis was 97.5 mmol/L (IQR: 59.3-139.3). Natriuresis levels did not differ by sex. High values with statistically significant were presented in people under 30 years old, with low consumption of vegetables and increased consumption of fried food. The group of healthy subjects showed increased sodium excretion than those who reported diabetes or high blood pressure. Conclusions: The increased natriuresis occurs in young people without having pathological medical history and also having the worst eating habits. Public health policies must focus at this level to prevent future cardiovascular and renal disease it is at this level where public health must intervene to prevent future cardiovascular and renal disease.

Fator natriurético atrial: ele é o responsável pela hiponatremia e natriurese em neurocirurgia? / Atrial natriuretic factor: is it responsible for hyponatremia and natriuresis in neurosurgery?

RESUMO Objetivo: Avaliar a presença de hiponatremia e natriurese, bem como suas associações com o fator natriurético atrial em pacientes de neurocirurgia. Métodos: Foram incluídos 30 pacientes submetidos à ressecção de tumor intracraniano e à clipagem de aneurisma cerebral. Os níveis plasmáticos e urinários de fator natriurético atrial foram medidos durante os períodos pré e pós-operatório. Resultados: Hiponatremia esteve presente em 63,33% dos pacientes, particularmente no primeiro dia pós-operatório. Observou-se natriurese em 93,33% dos pacientes, principalmente no segundo dia pós-operatório. Os níveis plasmáticos de fator natriurético atrial estavam aumentados em 92,60% dos pacientes em pelo menos um dos dias pós-operatórios, mas não houve associação estatisticamente significante entre fator natriurético atrial e sódio plasmático, e entre fator natriurético atrial e sódio urinário. Conclusão: Após neurocirurgia, na maior parte dos pacientes, estiveram presentes hiponatremia e natriurese; contudo, o fator natriurético atrial não pôde ser considerado diretamente responsável por tais alterações nos pacientes neurocirúrgicos. Provavelmente, há o envolvimento de outros fatores natriuréticos.

ABSTRACT Objective: To evaluate the presence of hyponatremia and natriuresis and their association with atrial natriuretic factor in neurosurgery patients. Methods: The study included 30 patients who had been submitted to intracranial tumor resection and cerebral aneurism clipping. Both plasma and urinary sodium and plasma atrial natriuretic factor were measured during the preoperative and postoperative time periods. Results: Hyponatremia was present in 63.33% of the patients, particularly on the first postoperative day. Natriuresis was present in 93.33% of the patients, particularly on the second postoperative day. Plasma atrial natriuretic factor was increased in 92.60% of the patients in at least one of the postoperative days; however, there was no statistically significant association between the atrial natriuretic factor and plasma sodium and between the atrial natriuretic factor and urinary sodium. Conclusion: Hyponatremia and natriuresis were present in most patients after neurosurgery; however, the atrial natriuretic factor cannot be considered to be directly responsible for these alterations in neurosurgery patients. Other natriuretic factors are likely to be involved.

Investigación de la ingesta de sal mediante natriuresis en escolares de 6 a 13 años de La Pampa / RESEARCH IN SALT INTAKE BY NATRIURESIS IN CHILDREN AGED 6 TO 13 THE PROVINCE OF LA PAMPA

Introducción: en la provincia de La Pampa prevalece una alta ingesta de carnes y fiambres. Existe promoción en adultos para disminuir la ingesta de sal, no focalizada en niños. Objetivos: investigar en escolares de la comunidad agrícolaganadera la ingesta de sal mediante la natriuresis y determinar riesgo de hipertensión arterial. Materiales y métodos: estudio piloto, exploratorio, descriptivo en 67 niños/niñas de 6-13 años, de escuela de jornada completa, sin restricción dietética. Se determinó frecuencia de ingesta de fiambres, peso, talla e IMC, perímetro de cintura mínima (cm) y un control de presión arterial (PA). Se describen los resultados según sexo, edad y percentiles (Pc) de talla (Task Force, 2004). Se determinó natriuresis (matutina y vespertina) e ingesta de sal (método de Tanaka, et al.). Se informaron los resultados a la familia y se educó sobre los factores de riesgo cardiovasculares. Resultados: el 96% consumía frecuentemente fiambres, el 14,66% tenía un Pc de PA anormal. Las niñas mayores de 9 años tuvieron mayor peso (p:0,01) e IMC que los varones (p:0,02). Los varones menores de 9 años tenían mayores niveles de natriuresis matutina que las niñas (p:0,04). La ingesta de sal/24 h de las niñas menores de 9 años fue de 2,48±1,99 g y 3,19±0,36 g en las mayores (p:0,09), siendo de 1,82±0,56 y 3,27±1,03 g respectivamente en los niños (p:0,01). Conclusiones: hallamos un consumo elevado de sal en la población estudiada, aumentando significativamente en varones a partir de los 9 años poniéndolos en riesgo de hipertensión arterial. Se debe efectuar un programa de alimentación saludable especialmente a partir de esta edad para el control de peso en las niñas y de la ingesta de sal en los niños, informando a los médicos responsables para que efectúen el control de la presión arterial en particular.

Advances in the Mechanism of Action of Natriuretic Peptides at a Cellular Level.

Background: Natriuretic peptides have a vast array of different actions at numerous sites throughout the human body. There have been rapid advances in understanding their mechanism of action in recent years and this review aimed to collate all available information on this field in order to present the current evidence-base. Method: A two-step process utilising a Medline/PubMed systematic search was conducted. The initial search was undertaken using elementary phrases. The search produced over 4000 published papers on the topic of the mechanisms of action of natriuretic peptides. The resultant abstracts were analysed and appropriate papers were selected. The secondary search was performed by (1) using the reference lists of the chosen articles and (2) by using PubMed weblink for related articles. The studies were selected if they were in English language published in the past 30 years (1983-2013) and included the appropriate topics. All of the reports regarding the intracellular and pharmacological mechanisms of action of natriuretic peptides were selected. Conclusions: This review has collected all information on the recent advances in our understanding of the intracellular pathways that allow these peptides to bring about natriuresis, vasodilatation and their many other effects. Although offering significant pharmacological potential, this field remains poorly understood and there is a need for more research using newer research techniques.

El efecto anti-hipertensivo de angiotensina-(1-9) es mediado por aumento temprano de la diuresis y natriuresis / Cardiac arrest associated to intramural hematoma of the anterior descending coronary artery

Introducción: Angiotensina (Ang)-(1-9) posee propiedades anti-hipertensivas y efecto protector a nivel cardiovascular en ratas hipertensas. Sin embargo, se desconoce si estos efectos están asociados a un mecanismo de desbalance de sodio a nivel renal. Objetivo: Determinar si el efecto anti-hipertensivo de Ang-(1-9) está asociado a un mecanismo diurético-na-triurético. Método: Ratas macho Sprague Dawley (200 ± 10g) fueron aleatorizadas para recibir Ang II (400 ng/kgmin) vía bomba osmótica. Como control se utilizaron ratas con operación sham (n=18). Después de 2 semanas desde la instalación de bomba, las ratas Sham e hipertensas fueron randomizadas para recibir vehículo (n=10), Ang-(1-9) (602 ng/kg/min, n=17) o una co-administración de Ang-(1-9) y A779 (100 ng kg-1min-1, n=7 bloqueador del receptor MAS) por 2 semanas. Resultados: Se determinó la presión arterial sistólica (PAS), masa ventricular relativa (MVR), área y perímetro de los cardiomiocitos (AC y PC) y la fracción volumétrica de colágeno total (FVCT). Para evaluar la diuresis y natriuresis se utilizaron ratas normotensas que fueron randomizadas para recibir vehículo (n=8) o Ang-(1-9) (600 ngKg-1min-1, n=8) por 6 días. Se observó un incremento significativo(p<0.05) de PAS (33%), MVR (17%), AC (64%), PC (20%), FVCT (46%). La administración crónica de Ang-(1-9) disminuyó PAS (20%), MVR (13 %), AC (35%), PC (20%) y FVCT (20%). Estos efectos no fueron mediados por el receptor MAS. Al comparar las ratas normotensas tratadas con vehículo o Ang-(1-9), se observó un aumento significativo de la diuresis y natriuresis en los días 2 y 3 en los animales con infusión de Ang-(1-9). Conclusión: Ang-(1-9) reduce la hipertensión y el remodelamiento cardíaco en ratas hipertensas. En animales normotensos se demostró que el tratamiento con Ang-(1-9)-induce diuresis y natriuresis. Este es el primer reporte que señala que el efecto de Ang-(1-9) está asociado a una regulación del sodio a nivel renal.

Background: Angiotensin-(1-9) has anti-hypertensive properties and protective cardiovascular effect in hypertensive rats. However, it is unknown whether its effects are related to a kidney mechanism to balance sodium. Aim: To determine if the anti-hypertensive effect of Ang-(1-9) is associated to a diuretic-natriuretic mechanism. Method: Sprague Dawley male rats (200±10 grs) were randomized to receive Angiotensin II by osmotic pump (400 ng/kg/min). Sham operated rats were utilized as control (n=18). Two weeks after pump setting, Sham rats with hypertension were randomized to receive placebo (n=10), Ang-(1-9)(602 ng/kg/min, n=17) or Ang-(1-9) plus A779 (Ang-(1-7) Receptor Mas blocker, 100ng/kg-1min-1, n=7) co-administration for two weeks. Arterial systolic pressure (PAS), ventricular relative mass (MVR), cardiomyocytes area and perimeter (AC and PC) and total collagen volume fraction (FVCT) were measured. Normotensive rats were utilized to evaluate diuresis and natriuresis which were randomized to receive placebo (n=8) or Ang-(1-9) (600ng/kg-1/min-1, n=8) for six days. Results: It was observed a significant rise (p<0.05) of PAS (33%), MVR (17%), AC (64%), PC (26%), FVCT (46%) was observed. Chronic administration of Ang-(1-9) reduced PAS (20%), MVR (13%), AC (35%), PC (20%) and FCVT (20%). All those effects were not mediated by Mas receptor. A significant raise was observed of diuresis and natriuresis at the second and third day of treatment in rats receiving Ang-(1-9) in comparison with normotensive rats treated with placebo. Conclusion: Ang-(1-9) reduces hypertension and cardiac remodeling in hypertensive rats. Ang-(1-9) induces natriuresis and diuresis in normotensive rats. This is the first report showing that Ang-(1-9) is associated to sodium balance in the kidney.

Evaluación de la ingesta dietética y excreción urinaria de sodio y potasio en adultos / Assessment of dietary intake and urinary excretion of sodium and potassium in adults

Background: Hypertension is associated with elevated sodium and low potassium intakes. The determination of sodium and potassium intake by dietary records is inaccurate, being its measurement from 24-h urine collection the reference method. Aim: To determine urinary sodium and potassium excretion in adults. To compare dietary sodium and potassium intake and their excretion from an isolated urine sample against the reference method. Material and Methods: Seventy healthy adults aged 35 ± 8 years with a body mass index 25 ± 2 kg/m² (36 women) were studied. Urine was collected over 24 h, including an isolated urine sample taken in fasting conditions. Additionally, three 24-h dietary records were performed. Results: Reported sodium and potassium intake was 2,720 ± 567 and 1,068 ± 433 mg/day, respectively. In turn, urinary excretion of sodium and potassium was 4,770 ± 1,532 and 1,852 ± 559 mg/day, respectively. These latter values were significantly higher than those obtained by dietary records. Furthermore, the urinary sodium and potassium excretion estimated from an isolated urine sample was 4,839 ± 1,355 and 1,845 ± 494 mg/day, respectively. These values were similar to those obtained with a 24 h urine collection. Conclusions: Dietary records underestimated electrolyte intake when compared with the reference method. Using an isolated urine sample to estimate electrolyte intake may be a reliable alternative.

Role of α2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham operation. Four weeks after 5/6 nephrectomy, serum bicarbonate levels were higher in the NACT-treated group. On the pressure-natriuresis curve, NACT-treated CRF rats were more salt-resistant than NACL-treated CRF rats. Additionally, the NACT-treated CRF group showed less tubulointerstitial damage than the NACL-treated CRF group. The expression and immunoreactivity of NHE3 in the kidney in the NACT-treated CRF group were lower than those in the NACL-treated CRF group. We observed that dietary NACT as alkali therapy in CRF might improve the altered salt-sensitivity and ameliorate the progression of kidney injury compared to the NACL diet, which may be related to reduced renal NHE3 expression.

Natriuria and calciuria levels in preeclampsia: a cross-sectional study / Valores de natriúria e calciúria na pré-eclâmpsia: estudo transversal

CONTEXT AND OBJECTIVE Sodium excretion abnormalities in preeclampsia have been studied in relation to several factors. The objective of this study was to compare natriuria (mEq/24 h) and calciuria levels (mg/24 h) in preeclamptic patients. DESIGN AND SETTING An analytical cross-sectional study with a control group was conducted in the obstetric center and the high-risk pregnancy outpatient clinic at a university hospital in southern Brazil, and in a primary healthcare unit in the same city, including pregnant women with mild preeclampsia, severe preeclampsia or chronic hypertension, and women with normal pregnancies (14 patients in each group). METHOD Natriuria was measured using an ion-selective electrode in an automated clinical chemistry analyzer (Hitache 917, Roche). All the patients collected 24-hour urine, at home or at the hospital, for analysis of proteins, creatinine, calcium, sodium and uric acid. Quantitative variables with asymmetrical distribution were described using the median, minimum and maximum, and were compared using the Kruskal-Wallis test. The results were logarithmically transformed, with one-way analysis of variance (ANOVA) by ranks and then the post-hoc Tukey test, and were analyzed by means of the Spearman correlation and receiver operating characteristic (ROC) curve. The significance level used was 0.05. RESULTS There were significant differences between the groups in comparing severe preeclampsia with chronic hypertension and severe preeclampsia with controls (P < 0.0001 for both measurements). CONCLUSION Natriuria levels may be lower in preeclampsia when associated with calciuria. Natriuria assessment is an additional test for differential diagnosis of hypertensive diseases in pregnancy, but is a poor predictor when used alone. .

CONTEXTO E OBJETIVO Alterações na excreção de sódio têm sido estudadas na pré-eclâmpsia relacionadas a vários fatores. O objetivo deste estudo foi comparar natriúria (mEq/24 h) com os níveis de calciúria (mg/24 h) em pacientes pré-eclâmpticas. ESTUDO E LOCAL Estudo transversal analítico com grupo controle foi realizado no Centro Obstétrico e no Ambulatório de Gestação de Alto Risco em um hospital universitário no sul do Brasil, e na Unidade Básica de Saúde na mesma cidade, incluindo gestantes com pré-eclâmpsia leve e grave, hipertensão crônica e gestações normais, com 14 pacientes em cada grupo. MÉTODO A natriuria foi dosada através da medida de íon eletrodo seletivo, utilizando analizadores automáticos de química clínica (Hitache 917 Roche). Todas as pacientes coletaram urina de 24 h, em casa ou no hospital, para análise de proteínas, creatinina, cálcio, ácido úrico e sódio. As variáveis quantitativas com distribuição assimétrica foram descritas por mediana, mínimo e máximo, e comparadas por teste Kruskal-Wallis. Os resultados foram transformados logaritmicamente, com ANOVA one-way por ranking e, posteriormente, teste post-hoc de Tukey, e foram analisados por médias de correlações de Spearman e curva ROC (receiver operating characteristic). O nível de significância adotado foi de 0.05. RESULTADOS Foram encontradas diferenças significativas entre os grupos quando comparados pré-eclâmpsia grave com hipertensão crônica e pré-eclâmpsia grave com controles (P < 0.0001 para ambas as medidas). CONCLUSÃO Natriúria pode estar reduzida na pré-eclâmpsia ...

Sistema renal e sua influência no controle em longo prazo da pressão arterial / The influence of the renal system in the long-term control of blood pressure

Os seres vivos são dotados de inúmeros sistemas biológicos para a manutenção da homeostase da pressão arterial. Esses sistemas são compostos por um conjunto de substâncias que permitem ao indivíduo responder a variações do meio interno ou a estímulos externos. A hipertensão arterial é considerada hoje um dos principais fatores de risco para a morbidade e mortalidade cardiovascular. A elevação da pressão arterial gera aumento proporcional na excreção urinária de sódio e água denominada pressão de natriurese. A presente revisão faz uma abordagem relevante sobre o sistema renal no controle em longo prazo da pressão arterial, descrevendo o mecanismo de natriurese pressórica, que corrige integralmente qualquer variação da pressão e as células justaglomerulares, que focam o sistema renina angiotensina aldosterona (SRAA), considerado um dos principais sistemas na regulação da pressão arterial e na homeostase eletrolítica. A pesquisa foi realizada a partir da revisão bibliográfica, sendo consultados artigos científicos localizados nas bases de dados Medline, Scielo e Lilacs publicados até 2010, utilizando como descritores: natriurese, pressão arterial, hipertensão arterial, SRAA e, adicionalmente, consulta de livros acadêmicos para complementação das informações sobre o controle da pressão arterial em longo prazo. Os critérios de inclusão foram artigos clínicos e de revisão que abordavam o tema. A regulação em longo prazo está diretamente associada a homeostase do volume extracelular, o qual é determinado pelo conteúdo de sódio, sendo o sistema renal o principal controlador da variação de excreção deste íon.

Living organisms are endowed with numerous biological systems for the maintenance of the homeostasis of arterial pressure. These systems are comprised of a number of substances that allow the person to respond to variations in the internal environment or external stimuli, like the renin angiotensin aldosterone system. Hypertension is considered one of the main risk factors for cardiovascular morbidity and mortality. The elevation of arterial pressure creates a proportional increase in urinary excretion of sodium and water, the so-called pressure-natriuresis. This review is an important approach to the role of renal system in the long term control of blood pressure. It describes the pressure natriuresis mechanism that can correct 100% of variation of blood pressure and the juxtaglomerular cells that compose the juxtaglomerular apparatus focusing on the renin-angiotensin system, which is considered one of the main systems responsible for regulating the blood pressure and electrolyte homeostasis. This research was based on the literature review of scientific papers published in journals of Medline, Scielo and Lilacs, which were published up to 2010 using as keywords: natriuresis, arterial pressure, hypertension and RAAS. Human physiology books were also used to complete the information about the maintenance and long term control of blood pressure. The criteria for inclusion were: clinical and review articles about the topic. The long term regulation is directly related the homeostasis of extracellular volume, which is determined by the sodium content, once the renal system is the main controller of this ion excretion.

Obesidad y excreción urinaria de sodio en niños y adolescentes / Obesity and urinary sodium excretion in children and adolescents

Background: Qbesity is a disease characterized by an abnormal accumulation body fat that results in neuroen-docrine changes that alter the homeostasis of sodium, producing an increased risk of hypertension in adulthood. objective: To evaluate the effect of obesity on urinary sodium excretion in children and adolescents. subjects and Methods: 266 male and female children in the age group of 5-15 years were studied: 154 obese (OB) with > 95th percentile of BMI, and 112 normal-weight patients (C) with percentile 5-85 of BMI, from the outpatient service of the Children Hospital, Posadas, Misiones, Argentina during the years 2008 -2009. The determinations of serum sodium (Na s) and 24-hour urine (Na ur) were performed using Ion Selective Electrode. The fractional excretion of sodium (FENa percent) was calculated. results: Na ur values (mEq/kg/day) and FENa percent reported significantly lower differences in the obese group compared to controls: OB Na ur 2.23 vs C Na ur 3.40 (p < 0.0001); OB FENa percent 0.59 vs C FENa percent 0.71 (p = 0.001). Conclusion: Results obtained in the present study showed that obese children have a significantly decreased urinary sodium excretion compared to normal weight children. This difference could be caused by renal retention of this ion.

Introducción: La obesidad es una enfermedad caracterizada por el aumento de grasa corporal, que genera modificaciones neuroendocrinas involucrando alteraciones en la homeostasis del sodio, que podrían generar hipertensión arterial en la adultez. Objetivo: Evaluar el efecto de la obesidad sobre la excreción urinaria de sodio en niños y adolescentes. Pacientes y Método: Se estudiaron 266 niños de ambos sexos, entre 5 y 15 años: 154 obesos (OB) definidos como IMC percentil > 95, y 112 normopeso (C), IMC percentil 5-85, provenientes del Servicio de Consultorio Externo del Hospital de Pediatría-Posadas, Misiones, Argentina, durante los años 2008-2009. Las determinaciones de sodio en suero (Na s) y orina de 24 h (Na ur) se realizaron con electrodo ion selectivo. Se calculó la excreción fraccional de sodio (EFNa por ciento). Resultados: Los valores de Naur (mEq/ kg/día) y la EFNa por ciento significativamente menores en el grupo de obesos con respecto a los controles: Na ur QB 2,23 vs Na ur C 3,40 (p < 0,0001); EFNa por ciento OB 0,59 vs EFNa por ciento C 0,71 (p = 0,001). Conclusión: En el presente estudio los resultados mostraron que los niños y adolescentes obesos presentan una disminución significativa de la excreción urinaria de sodio respecto de los niños normopeso. Dicha diferencia podría estar generada por la retención renal de dicho ion.

Role of nitric oxide in the diuresis and natriuresis occurring in patients with obstructive sleep apnoea syndrome.

Objective. To determine whether nitric oxide (NO) has any role in the diuresis and natriuresis observed in patients with obstructive sleep apnoea syndrome (OSAS). Methods. We measured 12-hour urine volume in the day and in the night in patients with OSAS (n=20) and determined the concentrations of urinary sodium and nitrate. The frequency of urination in the night was also noted. The measurements were done again after two nights of continuous positive airway pressure (CPAP) therapy and after putting the patients on oral anti-oxidant treatment (vitamin C–100mg BD and vitamin E–400IU BD) for 45 days. Ten healthy normal subjects underwent the same protocol except the CPAP therapy. Results. In patients with OSAS, the night urine volume and sodium concentration were similar and the nitrate levels were higher compared to those in the day. After CPAP therapy, while the urine volume and sodium concentration decreased, the nitrate level became similar to that in the day. Such effects were not observed after anti-oxidant treatment. The frequency of urination was decreased in both the instances. The effects observed after CPAP therapy were similar to those observed in control subjects with or without anti-oxidant treatment. Conclusion. Renal NO promotes diuresis and natriuresis in patients with OSAS.

Rol del riñón en la hipertensión sal-sensible / Role of the kidney in salt sensitive hypertension

An important proportion of patients with essential hypertension are salt sensitive, defined as those who experience signifcant blood pressure changes according to the amount of salt intake. They have a disturbance in the pressure induced natriuresis mechanism and their kidneys have functional and morphological alterations con-sistent with an acquired tubulointerstitial alteration, afferent arteriole damage and alteration of peritubular capillaries. All these alterations lead to disturbances in sodium load excretion under normal pressures. There is also an associated activation of kidney vasoconstrictor/salt retaining systems and a reduction in the vasodilator/ salt eliminating mechanisms. These alterations, that originate early in life, generate a new blood pressure level, that corrects natriuresis at the expense of a sustained hypertension.

Role of norepinephrine & angiotensin II in the neural control of renal sodium & water handling in spontaneously hypertensive rats.

Background & objectives: A wealth of information concerning the essential role of renal sympathetic nerve activity (RSNA) in the regulation of renal function and mean arterial blood pressure homeostasis has been established. However, many important parameters with which RSNA interacts are yet to be explicitly characterized. Therefore, the present study aimed to investigate the impact of acute renal denervation (ARD) on sodium and water excretory responses to intravenous (iv) infusions of either norepinephrine (NE) or angiotensin II (Ang II) in anaesthetized spontaneously hypertensive rats (SHR). Methods: Anaesthetized SHR were acutely denervated and a continuous iv infusion of NE (200 ng/min/kg) or Ang II (50 ng/min/kg) was instigated for 1 h. Three 20-min urine clearances were subsequently collected to measure urine flow rate (UV) and absolute sodium excretion (UNaV). Results: Higher UV and UNaV (P<0.05) were observed in denervated control SHR as compared to innervated counterparts. The administration of NE or Ang II to innervated SHR produced lower UV and UNaV (P<0.05 vs. innervated control SHR). Lower diuresis/natriuresis response to ARD was observed in NE-treated SHR compared to denervated control SHR (P<0.05). Salt and water excretions in denervated NE-treated SHR, however, were significantly higher (P<0.05) relative to the excretion levels in control denervated SHR. Conversely, there was a higher (all P<0.05) diuresis/natriuresis response to ARD when Ang II was administered to SHR compared to denervated control or innervated Ang II-treated SHR. Interpretation & conclusions: NE retains its characteristic antidiuretic/antinatriuretic action following ARD in SHR. Typical action of Ang II on salt and water excretions necessitates the presence of an intact renal innervation. Ang II is likely to facilitate the release of NE from renal sympathetic nerve terminals through a presynaptic site of action. Moreover, there is a lack of an immediate enhancement in the renal sensitivity to the actions of NE and Ang II following ARD in a rat model of essential hypertension.

Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion: Role of renal monoamine-oxidase / Perfiles de secreción de dopamina renal en la expansión de volumen para regular diuresis y natriuresis: Rol de la monoaminoxidasa renal

Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats U DA V (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 ± 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 ± 0.35 to 1.1 ± 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early U DA V peak to 3.2±0.72 (p < 0.01) and though, U DA V increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.

La dopamina (DA) intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V) durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO) y decarboxilasa de aminoácidos aromáticos (AADC) en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control), IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v.) y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.). Se observó que en C la U DA V (ng/30min/100gPC) aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05), disminuyendo posteriormente. IMAO mostró un patrón de liberación similar pero significativamente mayor que C a los 30 min de expansión (32.5 ± 2.20, p < 0.05). En este grupo la actividad de MAO disminuyó de 8.29 ± 0.35 a 1.1 ± 0.03 nmol/mg tejido/hora y aumentaron la diuresis y natriuresis por sobre los controles. En BNZ, el pico de U DA V observado a los 30 min de la expansión disminuyó a 3.2 ± 0.72 (p < 0.01), aunque luego de 60 minutos fue mayor que en C. BNZ disminuyó tanto la diuresis como la natriuresis. Podemos concluir que al comienzo de la expansión de volumen se produce un pico de excreción de dopamina renal hacia la orina. La enzima MAO juega un rol fundamental en esta respuesta.

Renal functional & haemodynamic changes following acute unilateral renal denervation in Sprague Dawley rats.

Background & objectives: Regulation of renal function and haemodynamics are under a direct control from the renal sympathetic nerves and renal denervation produces overt diuresis and natriuresis in several mammalian species. However, the inter-related series of changes in renal function and haemodynamics following acute renal denervation (ARD) is not fully understood. Thus, we aimed to investigate and relate the changes in renal function and haemodynamics following acute unilateral renal denervation in anaesthetized Sprague Dawley (SD) rats. Methods: Male SD rats were fasted overnight, anaesthetized with sodium pentobarbitone (60 mg/kg ip), denervated by application of phenol to the left renal artery and maintained on an intravenous (iv) infusion of isotonic saline for 2 h. Throughout this period, six urine and plasma samples were taken at 20-min intervals to study kidney function parameters. In a different set of experiments, renal nerve stimulation (RNS) was carried out to characterize the changes in renal vasoconstrictor responses following ARD. Results: Denervated animals showed significantly (P<0.05 vs. control innervated rats) higher urine flow rate (UFR), absolute sodium excretion (UNaV), fractional sodium excretion (FENa) and glomerular filtration rate (GFR). The renal vasoconstrictor responses to RNS were significantly (P<0.05) lower in denervated rats as compared to the innervated counterparts. However, no appreciable differences were seen in the mean arterial pressure (MAP), plasma sodium (PNa), basal renal blood flow (RBF) and basal renal vascular resistance (RVR) in both innervated and denervated SD rats. Interpretation & conclusions: Natriuresis, diuresis, enhanced GFR and impaired vasoconstriction in response to RNS are typical and instant responses to ARD in SD rats. Renal sympathetic nerves serve more important role in salt and water conservation than in dynamic autoregulation of RBF under normal sympathetic tone; yet, their effects on renal haemodynamics become more evident in the presence of augmented renal sympathetic nerve activity (RSNA).