RESUMO
Apparent resistant hypertension (aTRH) is a significant public health issue. Once low adherence to antihypertensive treatment has been ruled out and true resistant hypertension is diagnosed, aldosterone-direct-renin-ratio (ADRR) aids in the screening of an aldosterone-producing adenoma (APA) and primary aldosteronism (PA). Once PA and other secondary causes have been ruled out, the values of aldosterone and renin allow patients to be classified into phenotypes such as low renin hypertension (LRH), Liddle's-like (LLph), and primary hyperaldosteronism (PAph). These classifications could aid in the treatment decision-making process. However, optimal cut-off points for these classifications remain uncertain. This study aims to assess the prevalence of these phenotypes and the behavior of different cut-offs of the ADRR in an Afro-Colombian population with apparent resistant hypertension, as well to describe their sodium consumption. Afro-descendant individuals 18 years of age or older, diagnosed with resistant hypertension and attending to a primary care center in Colombia were recruited as volunteers. As part of the study, their plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured. The phenotypes were categorized into three groups based on multiple cut-off points from different authors: low renin and low aldosterone phenotype (LLph), low renin and high aldosterone phenotype (PAph), and high renin and high aldosterone phenotype, referred to as the renal phenotype (Rph). The prevalence of ADRR values exceeding the cut-off and phenotypes were calculated. A linear regression model was derived to assess the effect of sodium consumption with PAC, PRC and ADRR. A total of 88 patients with aTRH were included. Adherence to at least 3 antihypertensive medications was 62.5%. The median age was 56 years (IQR 48-60), 44% were female, and 20% had diabetes. The study found that the prevalence of ADRR values exceeding the cut-off ranged from 4.5 to 23%, while low-renin hypertension (LRH) varied from 15 to 74%, Rph was found in approximately 30 to 34% of patients, PAph in 30 to 51%, and the LLph in 15 to 41%, respectively, depending on the specific cut-off value by different authors. Notably, sodium consumption was associated with lower aldosterone (ß - 0.15, 95% CI [- 0.27, - 0.03]) and renin concentrations (ß - 0.75, 95% CI [- 1.5, - 0.02]), but ADRR showed no significant association with sodium consumption. There were no significant differences in prevalences between the groups taking < 3 vs ≥ 3 antihypertensive medications. Altered aldosterone-direct-renin-ratio, low renin hypertension, Liddle's-like, and primary hyperaldosteronism are prevalent phenotypes in patients within Afro-Colombian patients with apparent treatment-Resistant hypertension.
Assuntos
Aldosterona , Anti-Hipertensivos , Hipertensão , Fenótipo , Renina , Humanos , Renina/sangue , Aldosterona/sangue , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Anti-Hipertensivos/uso terapêutico , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/epidemiologia , População Negra , Idoso , Resistência a MedicamentosRESUMO
CONTEXT: The role of hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcomes remains controversial. OBJECTIVE: To investigate the impact of hormone parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcomes. METHODS: We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. The bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index, aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), and relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 - nondominant RASI) * 100. RESULTS: A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had the worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure was significantly more frequent in the patients with CS >50% [98.41% vs 42.86% (P < .001) and 41.94% vs 0% (P < .001)]. CS correlated with high aldosterone at diagnosis (P < .001) and low postoperative aldosterone levels at 1 month (P = .019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs 16.67%, P = .014). In multivariable analysis, a CS >50% was associated with complete biochemical cure [odds ratio (OR) 125, 95% confidence interval (CI) 11.904-5000; P = .001] and hypertension remission (OR 12.19, 95% CI 2.074-250; P = .023). CONCLUSION: A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral primary aldosteronism and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.
Assuntos
Glândulas Suprarrenais , Aldosterona , Cosintropina , Hidrocortisona , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glândulas Suprarrenais/irrigação sanguínea , Glândulas Suprarrenais/metabolismo , Aldosterona/sangue , Cosintropina/administração & dosagem , Adulto , Hidrocortisona/sangue , Prognóstico , Veias , Coleta de Amostras Sanguíneas/métodos , IdosoRESUMO
OBJECTIVE: To determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA). METHODS: We measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels. RESULTS: Log-aldosterone was positively associated with diastolic BP (ß = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (ß = -0.12, 95% CI: -0.26, 0.02) and highest (ß = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (ß = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03. CONCLUSION: Higher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.
Assuntos
Aldosterona , Peso ao Nascer , Pressão Sanguínea , Idade Gestacional , Saliva , Humanos , Feminino , Gravidez , México , Aldosterona/sangue , Adulto , Saliva/química , Pressão Sanguínea/fisiologia , Recém-Nascido , Modelos Lineares , Adulto Jovem , Estudos de CoortesRESUMO
El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.
Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Orosomucoide/análise , Biomarcadores/sangue , Lipocalinas/análise , Lipocalinas/sangue , Hiperaldosteronismo/sangue , Ensaio de Imunoadsorção Enzimática , Estudos Transversais , Estudos de Coortes , Renina/análise , Aldosterona/sangue , Pressão Arterial , Hiperaldosteronismo/diagnóstico , Hipertensão/diagnósticoRESUMO
INTRODUCTION AND OBJECTIVES: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD. MATERIALS AND METHODS: C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed. RESULTS: Mice fed with High-Na+/HFD showed a lower MR expression in liver (p = 0.01) and less steatosis on histology (p = 0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p = 0.028) and lower hepatic triglyceride content (p = 0.008). This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p < 0.05), and lower expression of pro-inflammatory and profibrotic markers compared to those mice fed a Low-Na+/HFD. Additionally, mice fed a High-Na+/HFD showed higher expression of salt-inducible kinase (SIK)-1 and lower expression of serum-and-glucocorticoid-inducible kinase (SGK)-1. Similar results were observed with the MCD diet model. CONCLUSION: We identified in two experimental models of NAFLD that High-Na+ diet content is associated to lower serum aldosterone levels and hepatic MR downregulation, associated to decreased steatosis and reduced de novo hepatic lipogenesis, proinflammatory and profibrotic markers. Decreased activation of hepatic MR seems to generate beneficial downstream inhibition of lipogenesis in experimental NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Mineralocorticoides/metabolismo , Sódio na Dieta/administração & dosagem , Aldosterona/sangue , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Triglicerídeos/metabolismoAssuntos
Aldosterona/sangue , Androstenos , Estradiol , Hipertensão , Síndrome do Ovário Policístico , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/sangue , Espironolactona/farmacologia , Adulto , Androstenos/administração & dosagem , Androstenos/efeitos adversos , Anti-Hipertensivos/farmacologia , Angiografia por Tomografia Computadorizada/métodos , Anticoncepcionais Orais Hormonais/administração & dosagem , Anticoncepcionais Orais Hormonais/efeitos adversos , Diagnóstico Diferencial , Combinação de Medicamentos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Seleção de Pacientes , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológicoRESUMO
The diagnosis of primary hyperaldosteronism (PHPA) has progressively increased over the last years and some authors consider it as the main cause of secondary hypertension. We studied the prevalence of PHPA in hypertensive patients followed at the Hypertension Unit from July 1999 to July 2017. A total of 2500 patients were included and diagnosis of PHPA was done in 79 of them (3.2%). It was more frequent in women (55.7%) with an increased incidence in the elderly, as compared to previous studies (27.8%). Initial diagnosis was suspected upon the presence of inappropriate kaliuria and metabolic alkalosis, associated to an aldosterone/plasma renin activity ratio > 30 (ng/dl)/(ng/ml/h). After confirmation of the presence of PA, imaging techniques to determine the etiology were performed. In this way, 29 cases (36.8%) of aldosterone-producing adenoma and 5 cases of bilateral adrenal hyperplasia with nodules were identified. Computed tomography identified the adenomas and hyperplasias with bilateral cortical nodules in all patients. Adrenalectomy and/or antialdosteronics were efficient in controlling blood pressure in 69.9% of cases. Of note in this series was the remission of stage 3 chronic renal failure in two cases, the high prevalence of hypercalciuric urinary lithiasis and a case of breast carcinoma after prolonged treatment with spironolactone.
El diagnóstico de hiperaldosteronismo primario (HPAP) aumentó en los últimos años y algunos autores lo consideran la principal causa de hipertensión arterial secundaria. Estudiamos la prevalencia de HPAP en el total de pacientes hipertensos atendidos en la Unidad de Hipertensión Arterial, en el período comprendido entre julio 1999 a julio 2017. Se incluyeron 2500 pacientes y en 79 se diagnosticó HPAP (3.2%). El HPAP fue más frecuente en mujeres (55.7%), observándose un incremento en la edad geriátrica con relación a estudios previos (27.8%). El diagnóstico se sospechó ante la presencia de kaliuria inapropiada y alcalosis metabólica, acompañada de un cociente aldosterona/actividad de renina plasmática superior a 30 (ng/dl)/(ng/ml/h). Tras su confirmación se realizaron estudios de imagen para determinar la etiología. Se detectaron así 29 casos (36.8%) de adenomas productores de aldosterona y 5 de hiperplasia bilateral suprarrenal con nódulos. La tomografía computarizada identificó el 100% de los adenomas y de las hiperplasias con nódulos corticales bilaterales. El tratamiento con suprarrenalectomía y/o antialdosterónicos resultó eficaz en el control de la presión arterial en el 69.9% de los casos. Se comentan aspectos particulares de esta serie, como la remisión de la insuficiencia renal, la elevada presencia de litiasis urinaria hipercalciúrica y la detección de un carcinoma de mama tras dosis prolongadas de espironolactona.
Assuntos
Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Idoso , Aldosterona/sangue , Estudos Transversais , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Masculino , Pessoa de Meia-Idade , Renina/sangue , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
El diagnóstico de hiperaldosteronismo primario (HPAP) aumentó en los últimos años y algunos autores lo consideran la principal causa de hipertensión arterial secundaria. Estudiamos la prevalencia de HPAP en el total de pacientes hipertensos atendidos en la Unidad de Hipertensión Arterial, en el período comprendido entre julio 1999 a julio 2017. Se incluyeron 2500 pacientes y en 79 se diagnosticó HPAP (3.2%). El HPAP fue más frecuente en mujeres (55.7%), observándose un incremento en la edad geriátrica con relación a estudios previos (27.8%). El diagnóstico se sospechó ante la presencia de kaliuria inapropiada y alcalosis metabólica, acompañada de un cociente aldosterona/actividad de renina plasmática superior a 30 (ng/dl)/(ng/ ml/h). Tras su confirmación se realizaron estudios de imagen para determinar la etiología. Se detectaron así 29 casos (36.8%) de adenomas productores de aldosterona y 5 de hiperplasia bilateral suprarrenal con nódulos. La tomografía computarizada identificó el 100% de los adenomas y de las hiperplasias con nódulos corticales bilaterales. El tratamiento con suprarrenalectomía y/o antialdosterónicos resultó eficaz en el control de la presión arterial en el 69.9% de los casos. Se comentan aspectos particulares de esta serie, como la remisión de la insuficiencia renal, la elevada presencia de litiasis urinaria hipercalciúrica y la detección de un carcinoma de mama tras dosis prolongadas de espironolactona.
The diagnosis of primary hyperaldosteronism (PHPA) has progressively increased over the last years and some authors consider it as the main cause of secondary hypertension. We studied the prevalence of PHPA in hypertensive patients followed at the Hypertension Unit from July 1999 to July 2017. A total of 2500 patients were included and diagnosis of PHPA was done in 79 of them (3.2%). It was more frequent in women (55.7%) with an increased incidence in the elderly, as compared to previous studies (27.8%). Initial diagnosis was suspected upon the presence of inappropriate kaliuria and metabolic alkalosis, associated to an aldosterone/plasma renin activity ratio > 30 (ng/dl)/(ng/ml/h). After confirmation of the presence of PA, imaging techniques to determine the etiology were performed. In this way, 29 cases (36.8%) of aldosterone-producing adenoma and 5 cases of bilateral adrenal hyperplasia with nodules were identified. Computed tomography identified the adenomas and hyperplasias with bilateral cortical nodules in all patients. Adrenalectomy and/o r antialdosteronics were efficient in controlling blood pressure in 69.9% of cases. Of note in this series was the remission of stage 3 chronic renal failure in two cases, the high prevalence of hypercalciuric urinary lithiasis and a case of breast carcinoma after prolonged treatment with spironolactone.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Tomografia Computadorizada por Raios X , Estudos Transversais , Estudos Retrospectivos , Renina/sangue , Aldosterona/sangue , Hiperaldosteronismo/complicações , Hiperaldosteronismo/sangueRESUMO
BACKGROUND: Maternal protein restriction causes sperm alterations in the offspring, most of which are associated with epididymal functions. Because fluid reabsorption/secretion dynamics in the epididymal environment play important roles in the process of sperm maturation and concentration, we investigated the effects of maternal protein restriction on the expression of aquaporins (AQP1 and AQP9), vascular endothelial growth factor (VEGFa), and its receptor VEGFr-2 in different stages of postnatal epididymal development. METHODS: Pregnant rats were divided into groups that received normoprotein (17% protein) and low-protein diets (6% protein) during gestation and lactation. After weaning, male rats only received the standard diet and were euthanized at the predetermined ages of 21, 44 and 120 days. RESULTS: Maternal protein restriction decreased AQP1 and AQP9 expression in the initial segment and caput epididymis compared to the increased expression of these proteins observed in the corpus and cauda at all ages. Although protein restriction reduced the microvasculature density (MVD) on postnatal day (PND) 21 and 44, the MVD was unaltered on PND 120. CONCLUSIONS: Maternal protein restriction changed the structure or function of the offspring's epididymis, specifically by affecting fluid dynamics and vasculogenesis in important stages of epididymis development.
Assuntos
Aquaporina 1/metabolismo , Aquaporinas/metabolismo , Dieta com Restrição de Proteínas , Epididimo/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Aldosterona/sangue , Animais , Animais Recém-Nascidos , Feminino , Masculino , Gravidez , Ratos , Testosterona/sangueRESUMO
The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (WT) mice, klotho-haploinsufficient ( kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine- kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher α-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.