Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.846
Filtrar
1.
PLoS One ; 15(8): e0237364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764816

RESUMO

OBJECTIVES: Uromodulin has been associated with arterial hypertension in genome-wide association studies, but data from clinical and preclinical studies are inconsistent. We here analyzed the association of serum uromodulin (sUmod) with arterial hypertension and vasoactive hormones in a population-based study. METHODS: In 1108 participants of the KORA F4 study aged 62-81 years, sUmod was measured and the association of sUmod with arterial hypertension was assessed using logistic regression models. The associations of sUmod with renin and aldosterone and with the vasoconstrictive prohormone C-terminal pro-endothelin-1 (CT-proET-1) were analyzed in 1079 participants and in 618 participants, respectively, using linear regression models. RESULTS: After multivariable adjustment including sex, age, eGFR, BMI, fasting glucose, current smoking, previous stroke and myocardial infarction, sUmod was inversely associated with arterial hypertension (OR 0.78; 95% CI 0.68-0.91; p = 0.001). SUmod was not significantly associated with renin and aldosterone after adjustment for sex, age and eGFR. However, sUmod was inversely associated with CT-proET-1 (ß -0.19 ± 0.04; p < 0.001) after adjustment for sex, age, eGFR, BMI, arterial hypertension, fasting glucose, current smoking, previous stroke and myocardial infarction. The association with CT-proET-1 was stronger in participants with hypertension (ß -0.22 ± 0.04) than in normotensive participants (ß -0.13 ± 0.06; p for interaction hypertension = 0.003 in the model adjusted for hypertension). CONCLUSIONS: SUmod was inversely associated with arterial hypertension and the vasoconstrictive prohormone CT-proET-1, suggesting direct or indirect effects of sUmod on blood pressure regulation.


Assuntos
Endotelina-1/sangue , Hipertensão/sangue , Fragmentos de Peptídeos/sangue , Uromodulina/sangue , Idoso , Aldosterona/sangue , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Renina/sangue
2.
Medicine (Baltimore) ; 99(29): e20826, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702825

RESUMO

RATIONALE: The typical clinical presentations of patients with primary aldosteronism (PA) include generalized weakness, fatigue, high blood pressure, and potassium deficiency. However, normotensive PA is rare. Therefore, an atypical presentation of normal blood pressure is a challenge for the diagnosis and treatment of PA. PATIENT CONCERNS: A 43-year-old, thin, and tall woman (body mass index, 18.6 kg/m) with generalized weakness for 1 day presented to our emergency department, where hypokalemia was a significant finding. The initial diagnosis was anorexia nervosa with the evidence of renal potassium wasting with low urinary sodium and chloride levels, metabolic alkalosis, normal blood pressure, and low body mass index. However, neither vomiting features nor other specific induced vomiting features were noted. DIAGNOSES: The laboratory examination revealed high plasma aldosterone level, low plasma renin activity, and extremely high aldosterone-to-renin ratio indicating the diagnosis of PA, confirmed via adrenal computed tomography. INTERVENTIONS: Surgical adrenalectomy was performed. Pathological diagnosis was a benign cortical adenoma. OUTCOMES: Patient's serum potassium level and hormonal status became normalized after surgical removal of adrenal adenoma. She fully recovered without any further sequelae. LESSONS: It is too early to rule out PA based on the presence of normal blood pressure in a patient with metabolic alkalosis and renal wasting hypokalemia. Moreover, PA should be considered in a normotensive patient with an unknown hypokalemic etiology to avoid delayed diagnosis and treatment.


Assuntos
Anorexia Nervosa/diagnóstico , Hiperaldosteronismo/diagnóstico por imagem , Hipopotassemia/diagnóstico , Adenoma/cirurgia , Adrenalectomia/métodos , Adulto , Aldosterona/sangue , Alcalose/etiologia , Anorexia Nervosa/psicologia , Pressão Sanguínea/fisiologia , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/patologia , Hiperaldosteronismo/cirurgia , Hipopotassemia/etiologia , Debilidade Muscular/etiologia , Renina/sangue , Sódio/urina , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
3.
Circ Heart Fail ; 13(7): e006827, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32635768

RESUMO

BACKGROUND: Black patients have higher rates of hospitalization for acute heart failure than other race/ethnic groups. We sought to determine whether diuretic efficiency is associated with racial differences in risk for rehospitalization after acute heart failure. METHODS: A post hoc analysis was performed on 721 subjects (age, 68±13 years; 22% black) enrolled in 3 acute heart failure clinical trials: ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure), DOSE-AHF (Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure), and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Repeated-measures ANOVA was used to test for a race×time effect on measures of decongestion. Diuretic efficiency was calculated as net fluid balance per total furosemide equivalents. In a subset of subjects, Cox regression was used to examine the association between race and rehospitalization according to plasma renin activity (PRA). RESULTS: Compared with nonblack patients, black patients were younger and more likely to have nonischemic heart failure. During the first 72 to 96 hours, there was greater fluid loss (P=0.001), decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide; P=0.002), and lower levels of PRA (P<0.0001) in black patients. Diuretic efficiency was higher in black than in nonblack patients (403 [interquartile range, 221-795] versus 325 [interquartile range, 154-698]; P=0.014). However, adjustment for baseline PRA attenuated the association between black race and diuretic efficiency. Over a median follow-up of 68 (interquartile range, 56-177) days, there was an increased risk of all-cause and heart failure-specific rehospitalization in nonblack patients with increasing levels of PRA, while the risk of rehospitalization was relatively constant across levels of PRA in black patients. CONCLUSIONS: Higher diuretic efficiency in black patients with acute heart failure may be related to racial differences in activity of the renin-angiotensin-aldosterone system.


Assuntos
Afro-Americanos , Insuficiência Cardíaca/etnologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Grupos de Populações Continentais , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco
5.
Ann Otol Rhinol Laryngol ; 129(8): 806-812, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32249593

RESUMO

OBJECTIVE: The aim of this study was to investigate the serum renin levels of patients with idiopathic sudden sensorineural hearing loss (ISSNHL). MATERIAL AND METHODS: Twenty-four patients with ISSNHL and 24 asymptomatic healthy volunteers were included in the study. Subjects underwent pure-tone audiometry and serum renin levels were measured. RESULTS: There were 14 women (mean age:42.35 ± 9.53) and 10 men (mean age:43.8 ± 6.87) in the patient group. There were 14 women (mean age:42.4 ± 4.7) and 10 men (mean age:41.4 ± 4.59) in the control group. ISSNHL was detected on the right side in 13 patients and on the left side in 11 patients. Serum renin levels of the patients and controls were 788.01 ± 327.8 and 282.37 ± 107.73 pg/mL, respectively. The serum renin levels were found to be significantly higher in the patient group compared to the control group (P ≤ .001). There was a statistically significant strong positive correlation between serum renin level and the severity of hearing loss (r = 0.77; P = .001). CONCLUSION: Serum renin levels of patients with ISSNHL were higher than controls. There was a statistically significant strong positive correlation between serum renin level and the severity of hearing loss.


Assuntos
Perda Auditiva Neurossensorial/sangue , Perda Auditiva Súbita/sangue , Audição/fisiologia , Renina/sangue , Adulto , Audiometria de Tons Puros/métodos , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Am J Cardiol ; 125(12): 1794-1800, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32307090

RESUMO

Experimental studies support a link between activation of the renin-angiotensin-aldosterone system and cardiovascular disease (CVD). The relationship with subclinical atherosclerosis is uncertain. Among 1,699 individuals without prevalent CVD from the Multiethnic Study of Atherosclerosis, we measured plasma renin activity (PRA) and aldosterone. Using multivariable logistic regression with restricted cubic splines, we assessed continuous log-transformed PRA and aldosterone associations with the ankle-brachial index (ABI) and coronary artery calcium (CAC) scores (Agatston) with adjustment for cardiovascular disease (CVD) risk factors, kidney function, and inflammatory biomarkers. In fully adjusted models mutually adjusting for PRA and aldosterone, higher PRA was associated with an ABI <1.0 (p overall <0.001, p nonlinear = 0.02) and CAC Agatston score >300 (p overall = 0.02, p nonlinear = 0.22), while aldosterone was not associated with either outcome. For example, compared to the 10th percentile (0.16 ng/ml/hr) of PRA, the 90th percentile (2.68 ng/ml/hr) had 3.6 times (OR 3.62; 95% CI: 2.13 to 6.13) and 1.7 times higher odds (odds ratio 1.67; 95% confidence interval: 1.13 to 2.48) of ABI <1.0 and CAC >300, respectively. These associations persisted after adjustment for levels of C-reactive protein, Interleukin-6, and Tumor Necrosis Factor-alpha. There were no significant differences in these associations by race/ethnicity or antihypertensive medication status. In conclusion, in a multiethnic cohort of community-living adults without prevalent clinical CVD, PRA was associated with greater burden of subclinical peripheral artery and coronary artery disease. These findings provide additional evidence that PRA may have deleterious effects on cardiovascular health through an atherosclerotic pathway.


Assuntos
Aterosclerose/sangue , Doença da Artéria Coronariana/sangue , Doenças Vasculares Periféricas/sangue , Renina/sangue , Aldosterona/sangue , Índice Tornozelo-Braço , Biomarcadores/sangue , Feminino , Humanos , Inflamação/sangue , Testes de Função Renal , Masculino , Fatores de Risco , Calcificação Vascular/sangue
7.
Am Heart J ; 222: 199-207, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32105986

RESUMO

BACKGROUND: The effect of the renin angiotensin system on blood pressure (BP) values in young adults from the general population is not well studied. We investigated the relationship between the aldosterone-to-renin ratio (ARR) and various BP indices in this population. METHODS: We assembled a population-based sample of adults aged 25-41 years. Conventional and 24-hour BP recordings were obtained in all patients. Direct renin concentration and plasma aldosterone concentration were measured. Multivariable regression models were constructed to assess the relationships of ARR with BP and hypertension. RESULTS: We included 1,353 individuals (mean age 37 years, 56% women). The median (interquartile range) ARR, direct renin concentration, and plasma aldosterone concentration were 13.8 (8.7-22.9), 7.2 ng/L (4.4-11.0) and 94 ng/L (68-134). All BP indices were higher across sex-specific ARR quartiles. Per 1-unit increase in log-transformed ARR, the multivariable-adjusted ß-coefficients (95% CI) for conventional, 24-hour, daytime, and nighttime systolic BP were 1.68 (0.87-2.48), P < .0001; 2.40 (1.68-3.12), P < .0001; 2.23 (1.48-2.99), P < .0001; and 2.80 (2.03-3.58), P < .0001, respectively. Per 1-unit increase in log-transformed ARR, the multivariable-adjusted odds ratio (95% CI) for conventional, 24-hour, sustained and masked hypertension was 1.70 (1.17-2.28), P = .0004; 1.29 (1.06-1.56), P = .01; 1.82 (1.33-2.49), P = .002; and 1.14 (0.94-1.38), P = .20, respectively. CONCLUSIONS: In young adults, ARR was strongly associated with conventional and ambulatory BP. Our data suggest that an aldosterone-driven phenomenon occurs very early in the development of hypertension.


Assuntos
Aldosterona/sangue , Pressão Sanguínea/fisiologia , Hipertensão/sangue , Vigilância da População/métodos , Sistema Renina-Angiotensina/fisiologia , Renina/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Morbidade/tendências , Prognóstico , Suíça/epidemiologia
8.
Clin Chem ; 66(3): 483-492, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068832

RESUMO

BACKGROUND: Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system. METHODS: Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured. RESULTS: EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P < 0.01) correlations with DRC (r = 0.691) and PRA (r = 0.754) during FST. DRC and PRA were below their assays' functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P < 0.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P < 0.01) correlations with the ARR, whether renin was measured by DRC (r = 0.878) or PRA (r = 0.880). CONCLUSIONS: Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.


Assuntos
Angiotensina II/sangue , Hiperaldosteronismo/diagnóstico , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Idoso , Aldosterona/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Fludrocortisona/química , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Renina/sangue , Adulto Jovem
9.
Am J Case Rep ; 21: e920615, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31907345

RESUMO

BACKGROUND When mineralocorticoid receptor antagonist therapy is initiated for primary aldosteronism, the response of plasma renin activity indicates the level of cardiovascular risk. The purpose of this article was to compare the effect of mineralocorticoid receptor blockers on plasma renin activity levels in a patient with primary aldosteronism. CASE REPORT The patient was a 45-year-old male with severe hypertension. Because his aldosterone/renin ratio was high and a saline infusion test was positive, primary aldosteronism was diagnosed. Computed tomography revealed a low-density mass measuring 10 mm in the left adrenal gland. Segmental adrenal vein sampling demonstrated bilateral primary aldosteronism, so pharmacotherapy was started. Before treatment, his plasma renin activity was 0.5 ng/mL/hour. Eplerenone was commenced and the dose was increased to 100 mg/day. However, his plasma renin activity was still 0.8 ng/mL/hour and the maximum dose of eplerenone did not elevate plasma renin activity above 1 ng/mL/hour. Since plasma renin activity remained below 1 ng/mL/hour with mineralocorticoid receptor antagonist therapy, this patient was considered to have a higher cardiovascular risk than patients with essential hypertension. Accordingly, eplerenone was switched to esaxerenone, a new generation mineralocorticoid receptor blocker that became available in May 2019. After switching to esaxerenone (5 mg/day), the patient's plasma renin activity increased to 1.8 ng/mL/hour and subsequently remained at 1 ng/mL/hour or higher. CONCLUSIONS This is the first case report to present interesting changes of plasma renin activity in a primary aldosteronism patient after switching from eplerenone to esaxerenone. Elevation of plasma renin activity by esaxerenone in our primary aldosteronism patient reflected a mineralocorticoid receptor antagonistic effect that may have alleviated excessive mineralocorticoid receptor activation and volume expansion.


Assuntos
Eplerenona/uso terapêutico , Hiperaldosteronismo/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Pirróis/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/sangue , Sulfonas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade
10.
Urology ; 135: e1, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31604068

RESUMO

A 29-year-old female was referred to the urology clinic because of an incidentally found left renal mass discovered during workup for secondary erythrocytosis. Since 12 years of age, she has had headaches and poorly controlled hypertension refractory to trimodal antihypertensive therapy. Laboratory workup revealed markedly elevated aldosterone and renin levels. Computed tomography demonstrated a 3 cm left renal mass. The patient was admitted for intravenous blood pressure control. After partial nephrectomy, aldosterone and renin levels normalized. The patient was weaned off of blood pressure medications. Pathology was consistent with a juxtaglomerular cell tumor secreting renin (ie, reninoma).


Assuntos
Anti-Hipertensivos/farmacologia , Hipertensão/etiologia , Sistema Justaglomerular/patologia , Neoplasias Renais/complicações , Adulto , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Sistema Justaglomerular/diagnóstico por imagem , Sistema Justaglomerular/metabolismo , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Nefrectomia , Renina/sangue , Renina/metabolismo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Clin Exp Hypertens ; 42(1): 93-98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31204516

RESUMO

Introduction: There is no study evaluating the Tp-e/QT and Tp-e/QTc ratios with T wave peak to end interval (Tp-e interval) used for evaluation of cardiac arrhythmia risk and ventricular repolarization changes in patients with primary aldosteronism (PA). We aimed to investigate whether there was a change in Tp-e interval, Tp-e/QT and Tp-e/QTc ratios in patients with PA.Method: Thirty patients with newly diagnosed hypertension (HT) and PA and 30 patients with primary HT were included. Twelve-lead electrocardiography (ECG) was performed in all patients. Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were measured in addition to routine measurements in ECG.Results: Sodium, potassium, and plasma renin activity (PRA) were significantly lower in patients with PA; systolic and diastolic blood pressure, plasma aldosterone, plasma aldosterone/PRA were significantly higher in patients with PA (p < .05 for each one). When ventricular repolarization parameters were examined; while QT and QTc interval were similar between two groups, Tp-e interval, Tp-e/QT and Tp-e/QTc ratio values were significantly higher in patients with PA (p < .05 for each one). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio values were positively correlated with the serum calcium, aldosterone, and aldosterone/PRA levels and negatively correlated with serum sodium, potassium, renin levels (p < .05 for each one). In linear regression analyses, Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were independently associated with the aldosterone/PRA ratio.Conclusion: Tp-e interval, Tp-e/QT and Tp-e/QTc were increased in hypertensive patients with PA and were independently associated with aldosterone/PRA levels. This may be related to the changing neuroendocrine state in patients with PA.


Assuntos
Aldosterona/sangue , Ventrículos do Coração/fisiopatologia , Hiperaldosteronismo/fisiopatologia , Hipertensão/fisiopatologia , Renina/sangue , Adulto , Pressão Sanguínea , Cálcio/sangue , Doença do Sistema de Condução Cardíaco , Eletrocardiografia , Feminino , Humanos , Hiperaldosteronismo/complicações , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Sódio/sangue
13.
Surgery ; 167(1): 211-215, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31564486

RESUMO

BACKGROUND: Primary aldosteronism is a common cause of secondary hypertension. Treatment with adrenalectomy or mineralocorticoid receptor-blockers can prevent long-term adverse outcomes. This study aimed to determine primary aldosteronism screening rats in patients with hypertension in an underserved urban healthcare system. METHODS: We reviewed records of outpatient adults in an urban healthcare system from 2013 to 2017. Chart review along with International Statistical Classification of Diseases, 9th and 10th editions, diagnosis codes were used to identify patients meeting inclusion criteria for screening according to the 2016 Endocrine Society guidelines. The corresponding aldosterone, plasma renin activity, and 24-hour urine aldosterone values were identified. Multivariate logistic regression was performed to determine positive predictors of screening. RESULTS: Of 15,511 hypertensive patients seen, 6,809 (43.8%) met criteria for screening. Blacks were the most common racial group, and Medicare and Medicaid were the most frequent insurers. The aldosterone-to-renin ratio level was checked in 86 (1.3%) patients; 22 (25.6%) had an aldosterone-to-renin ratio >20. Of the 77 patients with hypertension and incidentaloma, 14 (18.2%) had an aldosterone-to-renin ratio checked. Additional positive predictors for being screened were hypertension and hypokalemia and sustained hypertension. CONCLUSION: Screening rates for primary aldosteronism in an underserved population are low. Proper identification of primary aldosteronism in those at risk could help ameliorate long-term effects of disease.


Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Hiperaldosteronismo/diagnóstico , Hipertensão/etiologia , Programas de Rastreamento/estatística & dados numéricos , Serviços Urbanos de Saúde/estatística & dados numéricos , Idoso , Aldosterona/sangue , Aldosterona/urina , Animais , Consenso , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/complicações , Hiperaldosteronismo/urina , Hipertensão/sangue , Hipertensão/urina , Masculino , Programas de Rastreamento/normas , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , New York , Guias de Prática Clínica como Assunto , Ratos , Renina/sangue , Estudos Retrospectivos , Estados Unidos , Serviços Urbanos de Saúde/normas , Populações Vulneráveis/estatística & dados numéricos
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1134-1135: 121856, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786420

RESUMO

Renin is the rate-limiting step within the renin-angiotensin-aldosterone system, but the reliable quantification of human endogenous renin levels by liquid chromatography coupled with mass spectrometry remains challenging. The complex sample matrix triggering ion suppression and the detection of the low-abundance as well as the proteolytical-resistant renin make a hybrid approach using immunocapture coupled with LC-HRMS a promising method for investigation. Therefore, in-silico digestion and BLAST® experiments were conducted in order to identify the unique amino acid sequence for mass spectrometric detection. To enhance mass spectrometric response, impacting parameters within the denaturation, alkylation, and digestion experiments were identified and optimized by a multistep Design of Experiments process. The optimal denaturation buffer consisted of RapiGest® and urea, leading to a signature peptide intensity increase of 56% at 20 °C, whereas the optimal reducing agent improved intensity by 27%. The most effective generation of signature peptide I was achieved using a high trypsin concentration and a low incubation temperature enhancing digestion by 75%. The applicability of this hybrid approach was confirmed in human matrix and allowed for a fivefold reduction in total assay procedure time without limiting the reliable quantification if compared to a conventional digestion approach.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Renina , Simulação por Computador , Humanos , Renina/sangue , Renina/química , Renina/metabolismo , Projetos de Pesquisa , Extração em Fase Sólida , Temperatura , Tripsina/metabolismo
15.
Presse Med ; 48(12): 1445-1455, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31761607

RESUMO

The Hormonal assessment of Arterial Hypertension (HTA) is an important part of the balance of resistant hypertension. This assessment - going well beyond the search for primary hyperaldosteronism (PHA) - requires a rigorous methodology and a robust experience of the nursing team within a dedicated unit: the HTA Day Hospital. If all the conditions are met and the assessment carried out well, it will allow a significant profitability since in this resistant hypertensive population it will detect a particular mechanism or secondary hypertension in 70% of patients. Since the diagnosis of PHA is essentially biological, the proper execution of the various stages of the assessment is essential to its documentation.


Assuntos
Técnicas de Diagnóstico Endócrino , Hormônios/análise , Hipertensão/diagnóstico , Aldosterona/análise , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/normas , Resistência a Medicamentos/efeitos dos fármacos , Hormônios/sangue , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Renina/análise , Renina/sangue
16.
Nat Commun ; 10(1): 5155, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727896

RESUMO

Gain-of-function mutations in the chloride channel ClC-2 were recently described as a cause of familial hyperaldosteronism type II (FH-II). Here, we report the generation of a mouse model carrying a missense mutation homologous to the most common FH-II-associated CLCN2 mutation. In these Clcn2R180Q/+ mice, adrenal morphology is normal, but Cyp11b2 expression and plasma aldosterone levels are elevated. Male Clcn2R180Q/+ mice have increased aldosterone:renin ratios as well as elevated blood pressure levels. The counterpart knockout model (Clcn2-/-), in contrast, requires elevated renin levels to maintain normal aldosterone levels. Adrenal slices of Clcn2R180Q/+ mice show increased calcium oscillatory activity. Together, our work provides a knockin mouse model with a mild form of primary aldosteronism, likely due to increased chloride efflux and depolarization. We demonstrate a role of ClC-2 in normal aldosterone production beyond the observed pathophysiology.


Assuntos
Aldosterona/sangue , Pressão Sanguínea , Canais de Cloreto/genética , Hiperaldosteronismo/sangue , Hiperaldosteronismo/fisiopatologia , Mutação/genética , Glândulas Suprarrenais/patologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Canais de Cloreto/química , Cloretos/urina , Citocromo P-450 CYP11B2/metabolismo , Modelos Animais de Doenças , Feminino , Heterozigoto , Hiperaldosteronismo/urina , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Renina/sangue , Sódio/urina
17.
Am J Case Rep ; 20: 1684-1690, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31732710

RESUMO

BACKGROUND Although the effect of percutaneous transluminal renal angioplasty (PTRA) on clinical outcomes has not been established in previous clinical studies, some case reports showed that PTRA drastically improved patient outcomes. The appropriateness of PTRA should be discussed in detail. CASE REPORT A 59-year-old man had been on treatment for hypertension for 5 years, but his blood pressure (BP) had been poorly controlled for the past 5 months. He was hospitalized for pulmonary edema due to heart failure with preserved ejection fraction (HFpEF). During hospitalization, ultrasound and plain computed tomography revealed atrophy of the right kidney, and laboratory investigations indicated secondary aldosteronism with high plasma renin activity (PRA). Unenhanced magnetic resonance imaging (MRI) suggested severe stenosis or occlusion of the right renal artery. PTRA was performed for total occlusion at the origin of the right renal artery, resulting in favorable dilation of the vessel and good blood flow. A differential renal vein renin assay showed a right-left difference of PRA before PTRA, but this disappeared after the procedure. Both PRA and the plasma aldosterone concentration were normalized after PTRA. In addition, the patient's BP decreased, proteinuria was reduced, diuretics could be discontinued, and his calcium channel blocker dosage was decreased. CONCLUSIONS The present case suggests that screening for renal artery stenosis by unenhanced MRI may be useful in patients who have HFpEF because PTRA can be used to achieve marked improvement of hypertension, endocrine abnormalities, and heart failure if stenosis is detected.


Assuntos
Aldosterona/sangue , Angioplastia , Insuficiência Cardíaca/terapia , Hipertensão Renovascular/terapia , Obstrução da Artéria Renal/terapia , Renina/sangue , Dispneia , Insuficiência Cardíaca/complicações , Humanos , Hipertensão Renovascular/complicações , Masculino , Pessoa de Meia-Idade , Obstrução da Artéria Renal/complicações
18.
Presse Med ; 48(11 Pt 1): 1265-1268, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732366

RESUMO

The two main non-iatrogenic causes of secondary hypertension in women of childbearing age are primary aldosteronism and renal fibromuscular dysplasia. It is recommended to look for a secondary hypertension in women who remain hypertensive three months after pregnancy, in patients under 40 years of age or in patients with a grade 3 HTN (BP≥180/110mm Hg) (Professional agreement). It is suggested that the initial assessment of a secondary HTN in women is performed by a HTN specialist; it will include an assessment of renin and aldosterone concentrations and an angio-CT of the renal arteries (or angio-MRI if contraindicated) (Grade C - Class 2).


Assuntos
Displasia Fibromuscular/complicações , Hiperaldosteronismo/complicações , Hipertensão/etiologia , Adulto , Fatores Etários , Aldosterona/sangue , Angiografia por Tomografia Computadorizada , Feminino , Displasia Fibromuscular/diagnóstico , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/sangue , Hipertensão/diagnóstico , Período Pós-Parto , Artéria Renal/diagnóstico por imagem , Renina/sangue , Fatores Sexuais
19.
BMC Infect Dis ; 19(1): 866, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638922

RESUMO

BACKGROUND: Hand, foot and mouth disease (HFMD) remains a burdensome health issue in mainland China. Enterovirus71 (EV-A71) is the main pathogen of severe HFMD. Continuous hemofiltration improves fluid overload, restores kidney function and alleviates inflammatory reactions. The aim of the present study was to evaluate the effects of continuous veno-venous hemodiafiltration (CVVHDF) on severe HFMD caused by EV-A71(EV-A71-HFMD) in a pediatric intensive care unit (PICU). METHODS: A retrospective observational study was performed in a tertiary university PICU from January 2012 to December 2016. Children with severe EV-A71-HFMD complicated by cardiopulmonary failure were included. The patients were divided into a CVVHDF group and a conventional therapy (control) group (non-CVVHDF). The demographics, characteristics, and outcomes between the groups were collected and analyzed. RESULTS: Twenty-nine patients with severe EV-A71-HFMD were enrolled. The 28-day mortality was 17.6% (3/17) in the CVVHDF group and 33.3% (4/12) in the non-CVVHDF group, with no statistical significance between the two groups (P = 0.403). The median interval between CVVHDF initiation and PICU admission was 6 (4,8.5) hrs, and the median duration of CVVHDF was 48 (36, 64) hrs. The left ventricular ejection fraction (LVEF) and cardiac index (CI) in the CVVHDF group were improved after treatment. The plasma levels of catecholamines and renin-angiotensin-aldosterone system (RAAS) substances in the CVVHDF group were significantly decreased after treatment. The decreased catecholamines and RAAS substances included adrenalin (169.8 [145.5, 244.6] vs. 148.0 [109.0, 208.1] ng/L, P = 0.033), dopamine (152.7 [97.0, 191.1] vs. 96.0 [68.0, 160.9] ng/L, P = 0.026), angiotensin II (185.9 [125.2, 800.0] vs. 106.0 [90.8, 232.5] ng/L, P = 0.047), aldosterone (165.7 [94.0, 353.3] vs. 103.3 [84.3, 144.3] ng/L, P = 0.033), and renin (1.12 [0.74, 3.45] vs. 0.79 [0.52, 1.25] µg/L/h, P = 0.029), CONCLUSIONS: CVVHDF reduced the levels of catecholamines and RAAS substances and improved cardiovascular function. Continuous hemodiafiltration may represent a potential therapy in patients with severe EV-A71-HFMD complicated with cardiopulmonary failure.


Assuntos
Doenças Cardiovasculares/terapia , Terapia de Substituição Renal Contínua , Enterovirus Humano A , Doença de Mão, Pé e Boca/terapia , Doença de Mão, Pé e Boca/virologia , Unidades de Terapia Intensiva Pediátrica , Doença Pulmonar Obstrutiva Crônica/terapia , Aldosterona/sangue , Angiotensina II/sangue , Doenças Cardiovasculares/complicações , Catecolaminas/sangue , Pré-Escolar , China , Feminino , Seguimentos , Doença de Mão, Pé e Boca/sangue , Doença de Mão, Pé e Boca/complicações , Hemodiafiltração/métodos , Humanos , Lactente , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Renina/sangue , Sistema Renina-Angiotensina/fisiologia , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento
20.
Eur J Endocrinol ; 181(5): 481-488, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505456

RESUMO

Background: HLA-G is an immune checkpoint molecule, naturally expressed during pregnancy, playing a critical role in the tolerance of the fetal semi-allograft from the maternal immune system. While HLA-G expression levels are associated with progesterone, the influence of other hormones is still unclear. Congenital adrenal hyperplasia (CAH) represents an adequate model to study the hormonal influence on biomarkers as it leads to impaired cortisol biosynthesis and increased progesterone and androgens production due to 21-hydroxylase enzyme deficiency. Methods: In a cross-sectional study of CAH patients matched on sex and age with healthy control, the association between circulating levels of soluble HLA-G and hormones was assessed by use of non-parametric analyses tests. Multivariable linear regressions were performed on normalized data. Results: Overall, 83 CAH patients and 69 healthy controls were included. Among CAH patients, all were under glucocorticoid and 52 (62.6%) were under mineralocorticoid supplementation. Compared to controls, CAH patients had increased HLA-G levels (15 vs 8 ng/mL, P = 0.02). In controls, HLA-G level was independently associated with progesterone and estradiol (ß = 0.44 (0.35-1.27) and -0.44 (-0.94, -0.26) respectively, both P values = 0.001). In CAH patients, HLA-G level was independently associated with mineralocorticoid supplementation dosage (ß = 0.25 (0.04-0.41), P = 0.001) and estradiol (ß = -0.22 (-0.57, -0.02), P < 0.001). Conclusion: CAH patients had higher HLA-G levels than healthy controls. HLA-G level was positively associated with progesterone and corticosteroid supplementation, and negatively with estradiol. The association between mineralocorticoid, renin and HLA-G levels may suggest a role of the renin-angiotensin system in the expression of soluble HLA-G.


Assuntos
Hiperplasia Suprarrenal Congênita/metabolismo , Antígenos HLA-G/sangue , Hormônios/sangue , Corticosteroides/uso terapêutico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Adulto , Biomarcadores/sangue , Estudos Transversais , Estradiol/uso terapêutico , Feminino , Humanos , Masculino , Mineralocorticoides/sangue , Progesterona/uso terapêutico , Renina/sangue , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA