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Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.
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Acetazolamida , Diuréticos , Insuficiência Cardíaca , Ensaios Clínicos Controlados Aleatórios como Assunto , Acetazolamida/uso terapêutico , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/mortalidade , Doença Aguda , Diuréticos/uso terapêutico , Inibidores da Anidrase Carbônica/uso terapêutico , Resultado do Tratamento , IdosoRESUMO
This research demonstrates the diuretic effect of naringenin, a flavanone aglycone found in citrus, on spontaneously hypertensive female and male rats (SHR). The data reinforces existing literature findings that male SHR exhibits higher systolic blood pressure than age-matched females. Urine volume assessed over 8â hours was lower when obtained from SHR males than females. When these animals were orally treated with different doses of naringenin (0.1-1â mg/kg), this increased urinary volume in both genders at the highest dose tested. In contrast, the lowest dose promoted a significant natriuretic effect. The other electrolytes analyzed in urine were not significantly altered, except potassium excretion, which was shown to be increased in the urine of SHR males. Furthermore, naringenin showed promise in reducing calcium oxalate (CaOx) crystal formation in an inâ vitro model, presenting potential advantages in lithiasis prevention.
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Hipertensão , Urolitíase , Ratos , Feminino , Masculino , Animais , Ratos Endogâmicos SHR , Natriurese/fisiologia , Hipertensão/tratamento farmacológico , Hipertensão/prevenção & controle , Diurese/fisiologia , Urolitíase/tratamento farmacológico , Urolitíase/prevenção & controleRESUMO
OBJECTIVES: The diuretic and kidney protective effect of the 3-demethyl-2-geranyl-4-prenylbellidifoline (DGP) were evaluated in rats. METHODS: The normotensive (NTR) and spontaneously hypertensive rats (SHR) received, once a day for 7 days, oral treatment with DGP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (10 ml/kg). Urine, blood, and kidney samples were collected for further analysis. KEY FINDINGS: The urine and Na+ elimination content were significantly higher in the groups that received DGP. Furthermore, a Ca2+-sparing action was detected in the urine of DGP-treated groups, which was consistent with the reduction in calcium oxalate crystal formation. Relevantly, the treatment did not change the parameters examined in the blood. Concerning the renal analyses, DGP treatment recovered the morphological damages of the kidney corpuscle area of SHR. In addition to the differences observed between the NTR and SHR vehicle groups, DGP augmented the amount of reduced glutathione and the activity of glutathione S-transferase GST while reducing the catalase and N-acetyl-ß-D-glucosaminidase activity and nitrite levels. CONCLUSION: Together, this study displayed the prolonged diuretic action of DGP and its natriuretic, Ca2+-sparing, and antiurolytic effects. The antioxidative and anti-inflammatory effects of DGP were evidenced in SHR kidneys, opening perspectives for further studies regarding the benefits of this xanthone.
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Hipertensão , Xantonas , Ratos , Animais , Diuréticos/farmacologia , Hipertensão/tratamento farmacológico , Cálcio , Rim , Ratos Endogâmicos SHR , Pressão Sanguínea , Xantonas/farmacologiaRESUMO
BACKGROUND: Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus (DM). It has been proposed that modifications in the function of proximal tubule epithelial cells (PTECs) precede glomerular damage during the onset of DKD. This study aimed to identify modifications in renal sodium handling in the early stage of DM and its molecular mechanism. METHODS: Streptozotocin (STZ)-induced diabetic BALB/c mice (STZ group) and LLC-PK1 cells, a model of PTECs, were used. All parameters were assessed in the 4th week after an initial injection of STZ. RESULTS: Early stage of DKD was characterized by hyperfiltration and PTEC dysfunction. STZ group exhibited increased urinary sodium excretion due to impairment of tubular sodium reabsorption. This was correlated to a decrease in cortical (Na++K+)ATPase (NKA) α1 subunit expression and enzyme activity and an increase in O-GlcNAcylation. RNAseq analysis of patients with DKD revealed an increase in expression of the glutamine-fructose aminotransferase (GFAT) gene, a rate-limiting step of hexosamine biosynthetic pathway, and a decrease in NKA expression. Incubation of LLC-PK1 cells with 10 µM thiamet G, an inhibitor of O-GlcNAcase, reduced the expression and activity of NKA and increased O-GlcNAcylation. Furthermore, 6-diazo-5-oxo-L-norleucine (DON), a GFAT inhibitor, or dapagliflozin, an SGLT2 inhibitor, avoided the inhibitory effect of HG on expression and activity of NKA associated with the decrease in O-GlcNAcylation. CONCLUSION: Our results show that the impairment of tubular sodium reabsorption, in the early stage of DM, is due to SGLT2-mediated HG influx in PTECs, increase in O-GlcNAcylation and reduction in NKA expression and activity.
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Diabetes Mellitus , Nefropatias Diabéticas , Camundongos , Suínos , Animais , Humanos , Túbulos Renais Proximais/metabolismo , Rim/metabolismo , Nefropatias Diabéticas/metabolismo , Sódio/metabolismo , Adenosina Trifosfatases/metabolismo , Diabetes Mellitus/metabolismoRESUMO
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.
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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.
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.
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Insuficiência Cardíaca , Sódio , Humanos , Feminino , Idoso , Masculino , Prognóstico , Estudos de Casos e Controles , Estudos ProspectivosRESUMO
Hesperidin (HSP) is a major flavanone glycoside in citrus fruits, including sweet oranges and lemons. It demonstrates numerous pharmacological activities, such as antihypertensive effects and cardiac and kidney tissue protection. However, its effect on modulating renal function has yet to be properly explored. Female and male Wistar spontaneously hypertensive rats (SHR) were used to test the effect of HSP on renal function. The rats were divided into different groups, treated orally, and placed in metabolic cages for urine collection for 8 h. HSP, at doses of 0.3-3 mg/kg, led to an increase in urine volume in both female and male SHR. This effect was associated with increased Na+ elimination (3 mg/kg) without causing any change in K+ excretion or pH and conductivity values. When given HSP in combination with hydrochlorothiazide (HCTZ) or amiloride (AMLR), urine volume and Na+ elimination were significantly increased compared to the group that received only HSP. In relation to K+ excretion, the depleting effect of HCTZ and the sparing of AMLR prevailed in both groups. Pre-treatment with a non-selective cholinergic receptor antagonist, atropine, partially prevented HSP-induced diuresis and natriuresis in male SHR, but this effect was not demonstrated with the non-selective inhibitor of the enzyme cyclooxygenase, indomethacin. This study shows the diuretic action of HSP in hypertensive rats, an activity probably associated with the cholinergic pathway. Although various biological actions have already been defined for HSP, this pioneering research reveals its potential as a diuretic medicine.
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ETHNOPHARMACOLOGICAL RELEVANCE: Tagetes erecta L., known as marigold, belongs to the Asteraceae family and is mainly found in South America. Despite reports that T. erecta flowers are used in folk medicine to treat cardiovascular and renal diseases, there is no study regarding its diuretic effect. AIM: This study aimed to evaluate the chemical composition and the diuretic efficacy of the hydroethanolic extract from T. erecta (HETE) in normotensive (NTR) and hypertensive (SHR) rats. MATERIAL AND METHODS: The HETE was analyzed by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Female and male NTR and SHR received the treatment with vehicle, HETE (0.01 mg/kg, 0.1 mg/kg, and 1 mg/kg) or hydrochlorothiazide (HCTZ; 5 mg/kg) orally. The urinary parameters were measured at the end of the 8-h experiment. RESULTS: From HETE, saccharides and triterpenes were the main annotated compounds, such as erythrodiol and ß-amyrin. The urine volume was significantly increased in the groups treated with HETE, in both male and female NTR and SHR rats, compared to the respective vehicle-treated groups. Regarding electrolytes elimination, the treatment with HETE did not reveal significant changes in the urine levels of K+ or Cl-, but it showed a natriuretic and Ca2+-sparing effects. The HETE beneficial result in reducing Ca2+ excretion was confirmed through the protective effect found in front of the urinary calcium oxalate precipitation and crystallization. The combination with HCTZ, a classic diuretic and saluretic medicine, significantly enhanced HETE-induced diuresis, natriuresis, and the Ca2+-sparing effect. On the other hand, the K+-sparing action was improved in the combination of HETE with amiloride, a standard K+-sparing diuretic. In contrast, the combination of HETE with atropine (a non-selective muscarinic receptor antagonist) and indomethacin (an inhibitor of the cyclooxygenase enzyme), promoted an important reduction in urinary volume, but interestingly the natriuretic effect was maintained. CONCLUSION: This study contributed to the preclinical validation of the diuretic efficacy of T. erecta, highlighting this species as promising for the development of new pharmacological strategies for the management of kidney disorders.
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Diuréticos/farmacologia , Flores/química , Hipertensão/tratamento farmacológico , Natriurese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tagetes/química , Animais , Pressão Sanguínea/efeitos dos fármacos , Diurese/efeitos dos fármacos , Diuréticos/química , Feminino , Masculino , Fitoterapia , Extratos Vegetais/química , Plantas Medicinais , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
Atrial natriuretic peptide belongs to the family of natriuretic peptides, a system with natriuretic, diuretic, and vasodilator effects that opposes to renin-angiotensin system. In addition to its classic actions, atrial natriuretic peptide exerts a nephroprotective effect given its antioxidant and anti-inflammatory properties, turning it as a beneficial agent against acute and chronic kidney diseases. This minireview describes the most relevant aspects of atrial natriuretic peptide in the kidney, including its renal synthesis, physiological actions through specific receptors, the importance of its metabolism, and its potential use in different pathological scenarios.
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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.