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.

The Potential Cardioprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors / 임상당뇨병

The potential mechanism by which sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent cardiovascular disease (CVD) is being widely investigated. Improved insulin resistance, along with decreased body fat mass associated with SGLT2 inhibitor treatment is consistent with previously well-established factors contributing to the prevention of CVD. These factors are responsible for reduction of oxidative stress as well as improvement of systemic inflammation. Because heart failure was one of the most dramatically improved cardiovascular events in various clinical trials and because SGLT2 inhibitors promote osmotic diuresis and natriuresis, hemodynamic changes are considered as a critical mechanism responsible for the cardioprotective effect of SGLT2 inhibitors. Restored tubuloglomerular feedback by SGLT2 inhibitors might play a role in renoprotection, which in turn, leads to fewer CVDs. Finally, blood ketone body increments in response to SGLT2 inhibition might act as a “super-fuel” for salvaging the failing diabetic heart.

Efeito agudo da drenagem linfática manual sobre a natriurese e lipólise de mulheres jovens / Acute effect of manual lymphatic drainage on natriuresis and lipolysis in young women

Fundamentos: A importância da validação científica de técnicas coadjuvantes a diversos tratamentos de saúde é inquestionável. Desta forma, a influência da drenagem linfática manual (DLM) na natriurese e na lipólise sob interação de anticoncepcional oral precisa ser investigada. Objetivos: Avaliar o efeito agudo da DLM sobre a natriurese e lipólise de mulheres jovens usuárias ou não de anticoncepcional oral. Método: Participaram 29 mulheres não usuárias de anticoncepcional oral e 29 usuárias, autodeclaradas saudáveis, sedentárias e eutróficas. As análises foram realizadas em dois dias distintos, Controle (C), sem intervenção terapêutica e DLM. Nos dias C e DLM coletamos 4 amostras de urina com intervalos de 60 min. Seguimos o método de Leduc, abdomem e membros inferiores, durante 45 min. Analisamos o fluxo urinário e excreção urinária e sódio, glicerol e peptideo natriurético atrial. A normalidade dos dados foi analisada pelo teste Shapiro-Wilk. Os dados que não obedeceram à normalidade foram apresentados em mediana e intervalo interquartil (25%-75%), enquanto os que obedeceram foram apresentados em média ± erro padrão. O teste de Mann-Whitney foi usado para dados não pareados e Wilcoxon para dados pareados. Dados com normalidade foram avaliados pelo teste t-Student não pareado. O nível de significância estatística adotado foi de 5%. Resultados: O efeito agudo de uma sessão de DLM promove aumento da natriurese em mulheres não usuárias de anticoncepcional oral, por outro lado, em usuárias induz aumento na liberação de glicerol e de ANP

Background: The importance of scientific validation of supporting techniques to various treatments is unquestionable. In this context, the influence of manual lymphatic drainage (MLD) on natriuresis and lipolysis and its interaction with oral contraceptives still need to be investigated. Objectives: To evaluate the acute effect of MLD on natriuresis and lipolysis in young women using or not oral contraceptives. Methods: Twenty-nine non-users of oral contraceptives and 29 oral contraceptive users, self-reported healthy, sedentary, normal weight women were enrolled. Analyses were conducted on two different days ­ control (C), without therapeutic intervention and MLD day. Four urine samples were collected at 60-minute intervals. MLD was performed in lower limbs and abdomen for 45 min following the Leduc method. Urinary flow rat e and urinary sodium, glycerol and atrial natriuretic peptide excretion were analyzed. Data normality was tested by the Shapiro-Wilk test. Data without normal distribution were expressed as median and interquartile range (25%-75%), while normally distributed data were expressed as mean ± standard error. Mann-Whitney test was used for unpaired data and Wilcoxon test for paired data. Data with normal distribution were evaluated by the unpaired t-Student test. Statistical significance was set at 5%. Results: One MLD session had an acute effect on both groups, increasing natriuresis in non-users of oral contraceptives and glycerol and atrial natriuretic peptide excretion in oral contraceptive users. Conclusion: Oral contraceptives influence the effect of MLD on natriuresis

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.

Renal sodium handling and sodium sensitivity

The pathophysiology of hypertension, which affects over 1 billion individuals worldwide, involves the integration of the actions of multiple organ systems, including the kidney. The kidney, which governs sodium excretion via several mechanisms including pressure natriuresis and the actions of renal sodium transporters, is central to long term blood pressure regulation and the salt sensitivity of blood pressure. The impact of renal sodium handling and the salt sensitivity of blood pressure in health and hypertension is a critical public health issue owing to the excess of dietary salt consumed globally and the significant percentage of the global population exhibiting salt sensitivity. This review highlights recent advances that have provided new insight into the renal handling of sodium and the salt sensitivity of blood pressure, with a focus on genetic, inflammatory, dietary, sympathetic nervous system and oxidative stress mechanisms that influence renal sodium excretion. Increased understanding of the multiple integrated mechanisms that regulate the renal handling of sodium and the salt sensitivity of blood pressure has the potential to identify novel therapeutic targets and refine dietary guidelines designed to treat and prevent hypertension.

A Case of Cerebral Salt Wasting Syndrome in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) may present with area postrema syndrome, which is characterized by intractable vomiting and hiccups. Hyponatremia is common in NMOSD and is mostly associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). In contrast to SIADH, cerebral salt wasting syndrome (CSWS) causes hyponatremia, which is associated with severe natriuresis and extracellular volume depletion in patients with cerebral disease. To our knowledge, hyponatremia associated with CSWS has not been reported in a patient with NMOSD. Here, we describe a NMOSD presenting with hyponatremia, which may be caused by CSWS following area postrema syndrome.

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.

The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) Trial and Its Clinical Impact on Patterns of Prescription for Anti-Diabetes Medication / 임상당뇨병

Since 2008, the Food and Drug Administration has required cardiovascular (CV) safety trials for all anti-diabetic medications available in the USA. Thus, new agents like dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists have been tested in CV safety trials. The results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) were released last year. Of the sodium-glucose cotransporter 2 (SGLT2) inhibitors tested, empagliflozin demonstrated a CV benefit in this trial. Another study of the renal protective effects of empagliflozin was released this year. The mechanisms supporting the cardio- and reno-protective effects of empagliflozin remain controversial. Hemodynamic changes related to SGLT2 inhibitors via natriuresis and osmotic diuresis are one potential mechanism. The Canadian Diabetes Association and European Society of Cardiology recently suggested SGLT2 inhibitors as an optimal anti-diabetic medication for patients with type 2 diabetes with overt CV disease. Further studies elucidating the potential mechanisms of cardio- and reno-protective effects of SGLT2 are needed.

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.

Papel da dipeptidil peptidase IV na fisiopatologia da insuficiência cardíaca / Role of dipeptidyl peptidase IV in the pathophysiology of heart failure

Introdução/Objetivo: Este estudo teve como objetivo testar a hipótese de que a atividade e/ou expressão da dipeptidil peptidase IV (DPPIV), uma enzima que inativa peptídeos com ações cardioreno protetoras, como o peptídeo-1 semelhante ao glucagon (GLP-1) e o peptídeo natriurético cerebral (BNP), estaria associada a um pior prognóstico na insuficiência cardíaca (HF). Métodos: Injúria do miocárdio foi realizada através da ablação do ventrículo esquerdo (VE) por radiofrequência em ratos Wistar machos (200-250 g). Os ratos foram divididos em três grupos: Sham, HF e HF + inibidor de DPPIV (sitagliptina 200mg/kg/b.i.d). Seis semanas após a cirurgia, os animais foram alojados individualmente em gaiolas metabólicas durante 3 dias para avaliação da função renal. Atividade e expressão da DPPIV no plasma e coração foram medidas por espectrofotometria e por immunoblotting, respectivamente. Para a avaliação da função cardíaca um cateter de pressão-volume foi posicionado dentro da cavidade do VE. A análise histológica foi realizada para os parâmetros morfométricos. A atividade da DPPIV no plasma também foi medida em pacientes com HF (n = 190). Resultados: A atividade DPPIV e sua abundância estavam aumentadas em animais com HF em comparação com Sham. Além disso, a atividade de DPPIV no plasma se correlacionou positivamente com o volume diastólico final (R = 0,517; p < 0,001) e o peso do pulmão/peso corporal (R = 0,492; p < 0,01). Uma correlação negativa entre a atividade DPPIV plasmática e a fração de ejeção também foi observada (R = 0,602; p < 0,001). Curiosamente, os animais HF também exibiram um aumento da expressão/atividade de DPPIV no tecido cardíaco, especialmente em células endoteliais. Seis semanas de tratamento com o inibidor de DPPIV sitagliptina atenuou a disfunção cardíaca, fibrose intersticial, congestão pulmonar e infiltração de macrófagos. O tratamento com sitagliptina também elevou os níveis plasmáticos de GLP-1 ativo, e aumentou a ativação de vias de...

Aim: The present study aimed to test the hypothesis that the activity and/or expression of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates cardiorenal protective peptides including glucagon-like peptide-1 (GLP-1) and brain natriuretic peptide (BNP), would be associated with poorer outcomes in heart failure (HF). Methods: Experimental HF was induced in male Wistar rats (200-250 g) by left ventricular (LV) myocardial injury after radiofrequency catheter ablation. Rats were divided in three groups: Sham, HF and HF+DPPIV inhibitor (sitagliptin 200mg/kg/b.i.d). Six weeks after surgery, animals were individually housed in metabolic cages during 3 days for assessment of renal function. Plasma and heart DPPIV activity/expression were measured spectrophotometrically and by immunoblotting respectively. For evaluation of cardiac function a pressure-volume catheter was positioned into the LV cavity. Histological analysis was performed for morphometric parameters. Plasma DPPIV activity was also measured in patients (n = 190) with heart failure. Results: Plasma DPPIV activity and abundance were increased in animals with HF compared to Sham. Additionally, plasma DPPIV activity positively correlated with ventricular end diastolic volume (R² =0.517; p < 0.001) and lung/body weight (R² =0.492; p < 0.01). A negative correlation between plasma DPPIV activity and ejection fraction was also observed (R² =0.602; p < 0.001). Interestingly, HF animals also exhibited an increase of expression and activity of DPPIV in heart tissue, especially in endothelial cells. Six-week treatment with the DPPIV inhibitor sitagliptin attenuated cardiac dysfunction, mitigated cardiac hypertrophy, interstitial fibrosis, lung congestion and macrophage infiltration. Sitagliptin also raised the plasma levels of active GLP-1, increased activation of cardioprotective signaling pathways including PKA, and Akt; and reduced the levels of apoptosis and pro-inflammatory biomarkers compared...

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.

Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction.

Cerebral salt-wasting syndrome after hematopoietic stem cell transplantation in adolescents: 3 case reports

Cerebral salt-wasting syndrome (CSWS) is a rare disease characterized by a extracellular volume depletion and hyponatremia induced by marked natriuresis. It is mainly reported in patients who experience a central nervous system insult, such as cerebral hemorrhage or encephalitis. The syndrome of inappropriate antidiuretic hormone secretion is a main cause of severe hyponatremia after hematopoietic stem cell transplantation, whereas CSWS is rarely reported. We report 3 patients with childhood acute leukemia who developed CSWS with central nervous system complication after hematopoietic stem cell transplantation. The diagnosis of CSW was made on the basis of severe hyponatremia accompanied by increased urine output with clinical signs of dehydration. All patients showed elevated natriuretic peptide and normal antidiuretic hormone. Aggressive water and sodium replacement treatment was instituted in all 3 patients and 2 of them were effectively recovered, the other one was required to add fludrocortisone administration.

Natriuresis y hemodinámica glomerular en un incomprendido sistema renina angiotensina aldosterona / Nutriuresis and Glomerular Hemodynamics in misunderstood Renin-angiotensin-aldosterone system

La respuesta natriur‚tica y la hemodin mica glomerular dependen de diversos sistemas de regulaci¢n intrarrenal; sin embargo, la mayor¡a de ellos posee alg£n grado de dependecia del sistema renina angiotensina. La distribuci¢n tisular y el efecto hemodin mico de este sistema son de vital importancia para el entendimiento de la regulaci¢n natriur‚tica y del filtrado glomerular en diversas enfermedades que se caracterizan por desregulaci¢n del equilibrio del sodio o del filtrado glomerular, tales como el s¡ndrome nefr¢tico, la falla renal aguda y cr¢nica e hipertensi¢n arterial.

Natriuretic response and glomerular hemodynamics depend on various intrarenal regulation systems; however, most of them possess some degree of dependence on the renin-angiotensin system. Tissue distribution and hemodynamic effects of this system are of vital importance for understandinf of the natriuretic and glomerular filtration regulation in the context of different diseases characterized by dysregulation of sodium balance or glomerular filtration rate, such as nephrotic syndrome, acute and chronic renal failure and hypertension.

Efecto diurético agudo de los extractos etanólico y acuoso de Ceratopteris pteridoides (Hook) en ratas normales / Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats

Introducción. Ceratopteris pteridoides es un helecho semiacuático de la familia Parkeriacea, ampliamente utilizado en la medicina popular colombiana como diurético y colelitiásico, sobre el cual no existen reportes científicos que avalen su uso popular como diurético. Objetivo. Evaluar el efecto diurético agudo en dosis única y dosis repetidas a corto plazo, de los extractos etanólico y acuoso de C. pteridoides en un modelo in vivo . Materiales y métodos. El extracto etanólico total fue obtenido por maceración de la planta entera de C. pteridoides con etanol y el extracto acuoso fue obtenido por decocción a 60 °C por 15 minutos. Ambos extractos se sometieron a análisis fitoquímico preliminar y estudio histológico posterior a la administración de los extractos durante ocho días consecutivos (1.000 mg/kg). El efecto diurético se evaluó en ratas Wistar, tratadas con los extractos (500 mg/kg), en forma aguda y en dosis repetidas a corto plazo, cuantificando la eliminación de agua y la excreción renal de sodio y potasio por espectrofotometría de absorción atómica y, de cloruros, por titulación mercurimétrica. Resultados. En el modelo agudo, ambos extractos mostraron un significativo efecto diurético y de excreción renal de sodio y potasio en comparación con el control, mientras que con la administración en dosis repetidas a corto plazo mostraron efecto diurético sin eliminación de electrolitos. El estudio histopatológico no sugirió efectos tóxicos hepáticos o renales. Conclusión. Los resultados demuestran la actividad diurética de C. pteridoides y sustentan el uso popular dado a esta planta como diurético en la costa norte colombiana. Se requieren estudios posteriores que permitan aislar e identificar los compuestos responsables de la actividad y los mecanismos de acción involucrados.

Introduction. Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. Objective. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. Materials and methods. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. Results. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. Conclusion. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

In vivo and in vitro anti-natriuretic activity of twigs fraction from Dorstenia picta: a possible mechanism

The present study examine the in vivo effects of Dorstenia Picta [D. picta] on urinary volume and sodium excretion in streptozotocin-induced diabetic rats, and determine a possible mechanism by which the extract increased sodium transport in A6 cells monolayers. Administration of the plant extract at the dose of 150 mg/kg during two weeks decreased urinary volume and sodium excretion. In vitro study showed that, apical application of the plant extract at the dose of 100 micro g/mL does not significantly increase sodium transport, whereas basolateral administration provoked a significant [P<0.05] increase of sodium transport in a concentration-dependent manner. The plant extract increases the sodium transport by 69.93% versus 55.41% for insulin and 78.44% for adenosine after 30 min. Preincubation of A6 cells monolayers with inhibitor of all adenosine receptors completely suppressed adenosine and plant extract stimulated sodium transport. Interesting is that, the A1 inhibitor receptor [DPCPX], at 100 nM completely abolished the effect of plant extract. The plant extract increased sodium transport by increase PI3-kinase activity and this effect is strongly inhibited by LY-294002. These data also suggest that, the twigs methanol fraction from Dorstenia picta increase sodium transport via PI 3-kinase pathway and requires A1 adenosine receptor

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.

A Case of Cerebral Salt Wasting Syndrome after Surgical Excision of a Giant Acoustic Neuroma / 대한이비인후과학회지

Cerebral Salt Wasting Syndrome (CSWS) is defined as the development of extracellular volume depletion due to a dysfunction of the renal sodium transport system. Differentiation of CSWS from the Symdrome of Inappropriate Secretion of Antidiuretic Hormone in patients with intracranial disease is difficult because both syndromes include hyponatremia and concentrated urine with natriuresis. However, distinguishing between these two syndromes is very important because the treatment options differ. We report a 41 year-old Asian woman who presented initially with hyponatremia, and was finally diagnosed with CSWS after an operation for an acoustic neuroma. Based on this case, we discuss a possible mechanism and disclose insights about differential diagnosis thereof.

Cerebral Salt Wasting Treated with Fludrocortisone in a 17-Year-Old Boy

Cerebral salt wasting is characterized by inappropriate natriuresis and volume contraction with associated cerebral pathology. It is distinct from the syndrome of inappropriate antidiuretic hormone secretion, which is characterized by inappropriate retention of free water. We report a patient with a porencephalic cyst who developed cerebral salt wasting. His initial treatment was supplementation of water and salt, which did not improve natriuresis or volume contraction. Fludrocortisone administration effectively managed the cerebral salt wasting.

Aproximación clínica al consumo de sodio / Clinical approach to sodium consumption

Introducción: el consumo de sodio se vincula directamente a las cifras de presión arterial y adicionalmente incide en el manejo de diversas enfermedades. En el año 2003, la Organización Mundial de la Salud (OMS) propone reducir el consumo poblacional de sal a menos de 5 g/día. En Uruguay no contamos con datos de mediciones directas del consumo de sodio. La medición del sodio en la orina de 24 horas es el método patrón para la determinación del consumo diario, sin embargo es un método poco usado en la prácticaclínica debido en parte a lo engorroso que resulta para el paciente. Objetivo: determinar el consumo de sodio de un grupo de voluntarios a través de la natriuria de 24 horas. Encontrar una relación entre la natriuria de una muestra de orina (spot) y la natriuria de 24 horas. Material y método: se reclutaron estudiantes de cuarto año de la carrera de Doctor en Medicina de la Universidad de la República. Se registraron antecedentes médicos, medidas antropométricas, y de presión arterial en consultorio y se recolectó la orina de 24 horas. El análisis de la relación entre el contenido de sodio en el spot y en la orina de 24 horas serealizó mediante prueba de chi cuadrado.Resultados: 33 de 45 estudiantes completaron el estudio. El consumo promedio de sodio fue de 2,9±1,1 g/día. Una natriuria en el spot mayor a 75 mEq/L se asoció a un consumo de sodiomedido por natriuria de 24 horas mayor de 100 mEq/día (p<0,005), con una sensibilidad de 95% y especificidad de 63%.

Introduction: sodium consumption is closely related to blood pressure rates and it additionally affects the handlingof different diseases. In 2003, the World Health Organization (WHO) encouraged people to reduce the consumption of sodium to under 5 g/day. In Uruguay there is no data resulting from direct measurement of sodium consumption. Measuring sodium in the 24 hour urine is the standard method to determine daily consumption, although this method is rarely used in the clinical practice due to its being bothersome for patients. Objective: to determine sodium consumption for agroup of volunteers through 24 hours natriuria. To find a relationship between spot tests of urine natriuria and 24-hour urine natriuria. Method: fourth year medical students were recruited from the School of Medicine at the University of the Republic. Medical history, anthropometric measures and blood pressure in the polyclinic were recorded and the urine was collected during 24 hours. The analysis of the relationship between the content of sodium in the spot and in the 24- hour urine was performed through square chi.Results: 33 out of 45 students completed the study. Average consumption of sodium was 2.9 2,9±1,1 g/day. Natriuria in the spot greater than 75 mEq/L was associated to sodium consumption measured by 24-hour natriuria greater than 100 mEq/día (p<0,005), with a sensitivity of95% and a specificity of 63%.

Introdução: o consumo de sódio está diretamente relacionado aos valores da pressão arterial e também tem influenciasobre o manejo de varias doenças. Em 2003, a Organização Mundial da Saúde (OMS) lançou uma proposta para reduzir o consumo de sal da população aum valor inferior a 5 g/dia. No Uruguai não estão disponíveis dados de medições diretas do consumo de sal. O método padrão para determinação de consumo diário é o exame da urina de 24 horas; no entanto não é um método muito utilizado na prática clínica por ser muito trabalhoso para o paciente. Objetivo: conhecer o consumo de sódio de um grupo de voluntários determinando a natriúria de 24 horas. Encontrar uma relação entre a natriúria de uma amostra de urina (ôspotõ) e a natriúria de 24 horas. Material e método: foram recrutados estudantes doquarto ano do curso de Medicina da Universidad de la República. Foram registrados sus antecedentes médicos,medidas antropométricas, e pressão arterial no consultório e se realizou a coleta de urina de 24 horas. A análise darelação entre o conteúdo de sódio no ôspotõ e na urina de 24 horas foi realizado utilizando a prova do X quadrado. Resultados: 33 dos 45 estudantes completaram o estudo. O consumo médio de sódio foi de 2,9±1,1 g/dia. Uma natriúria do ôspotõ superior a 75 mEq/L foi associada ao consumo de sódio medido por natriúria de 24 horas superior a 100 mEq/dia (p<0,005), com uma sensibilidadede 95% e especificidade de 63%.