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BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are the recommended medical therapy for bilateral primary aldosteronism (BPA). Compared with essential hypertension (EH), patients with BPA have higher cardiocerebrovascular disease (CCVD). There is no consensus on the criteria to assess the effectiveness of medical therapy for BPA. OBJECTIVE: To investigate the incidence and the risk factors for CCVD after medical therapy of BPA. METHODS: We conducted a retrospective cohort study including 240 BPA patients treated with MRA. The post-treatment plasma renin activity (PRA) was defined as unsuppressed (PRA≥1ng/ml/h) otherwise, it was defined as suppressed. We analyzed the association of post-treatment PRA status with CCVD outcomes. RESULTS: 7.1% (17/240) of patients with BPA developed CCVD at a median follow-up of 5.0 (2.96,7.66) years. 57.1% of patients had PRA ≥ 1ng/ml/h after treatment. Patients with PRA <1ng/ml/h have a higher incidence of CCVD (12.6% vs. 2.9%, P < 0.05) and they are at greater risk than those with PRA ≥1ng/ml/h (HR=4.50, 95% CI: 1.47-13.83, P<0.05; adjusted HR=3.98, 95% CI: 1.22-13.02, P<0.05). CONCLUSION: Patients with BPA treated with pharmacological have a high incidence of CCVD. PRA may be an indicator that mineralocorticoids are being adequately antagonized.

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The authors investigated the antihypertensive effect of sacubitril/valsartan (Sac/Val) when switching from other drugs and assessed whether brain natriuretic peptide (BNP) or plasma renin activity (PRA) before drug switching was a predictor of blood pressure lowering after switching to Sac/Val. In 92 patients with treated hypertension, clinic blood pressure, plasma BNP, and PRA were examined before and after switching to Sac/Val. Clinic systolic and diastolic blood pressures significantly decreased after drug switching to Sac/Val (p < .0001, respectively). The level before drug switching of BNP had no correlation with the change in systolic blood pressure (Δ-SBP) before and after switching to Sac/Val, but that of PRA was significantly correlated with Δ-SBP (r = .3807, p = .0002). A multiple regression analysis revealed that PRA before drug switching was an independent determinant of Δ-SBP. Our findings suggest that low PRA may become a useful marker to predict the antihypertensive effect of switching to Sac/Val in treated hypertensive patients.

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Primary aldosteronism (PA) is the most common cause of endocrine arterial hypertension, and the suggested screening test for case detection is the aldosterone-to-renin ratio (ARR) or aldosterone-to-direct renin ratio (ADRR) based on radio-immunoassay (RIA) and chemiluminescence assay (CLIA), respectively. The objective of our study was to evaluate the reliability of CLIA for aldosterone and renin measurement and the diagnostic performance of ADRR. A prospective cohort of 1110 patients referred to a single laboratory medicine center underwent measurement of aldosterone and direct renin concentration (DRC) by CLIA and measurement of aldosterone and plasma renin activity (PRA) by RIA. Of 1110 patients, 640 obtained a final diagnosis of hypertension, and 90 of these patients were diagnosed with PA. Overall, between-method correlation was highly significant for aldosterone concentrations (R = 0.945, p < 0.001) and less strong but significant for DRC/PRA (R = 0.422, p < 0.001). Among hypertensive patients, in PA cases, the areas under the receiver operator characteristics (ROC) curves were 0.928 (95% confidence interval 0.904-0.954) for ADRR and 0.943 (95% confidence interval 0.920-0.966) for ARR and were comparable and not significantly different. The highest accuracy was obtained with an ADRR cut-off of 25 (ng/L)/(mIU/L), displaying a sensitivity of 91% and a specificity of 85%. The chemiluminescence assay for aldosterone and DRC is a reliable method for PA diagnosis compared to the classical RIA method.

Asunto(s)

Aldosterona , Hiperaldosteronismo , Mediciones Luminiscentes , Renina , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/sangre , Aldosterona/sangre , Renina/sangre , Femenino , Persona de Mediana Edad , Masculino , Mediciones Luminiscentes/métodos , Adulto , Curva ROC , Estudios Prospectivos , Hipertensión/sangre , Hipertensión/diagnóstico , Anciano , Reproducibilidad de los Resultados

RESUMEN

BACKGROUND: In many practices, the screening for primary aldosteronism relies on a single-blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). ARR levels vary between expert centers and repeated assays in the same individual, emphasizing the potential variability of this screening approach. A suppressed PRA to <1 ng/mL per h has been proposed as an alternative test to the ARR. METHODS: We compared 2 potential screening approaches to identify probable primary aldosteronism (ARR≥30 or ARR≥20 versus PRA suppressed below 1 ng/mL per h) in a cohort of 94 829 paired PRA and PAC samples submitted by clinicians to evaluate the presence of primary aldosteronism. RESULTS: Of 94 829 patients, 20.3% tested positive based on ARR≥20 (95% CI, 20.0%-20.5%), 13.9% based on ARR≥30 (95% CI, 13.6%-14.1%), versus 45.9% based on suppressed PRA (<1 ng/mL per minute [95% CI, 45.5%-46.2%]). In the PRA group, a range of aldosterone levels was observed: 5.5% had PAC >15 ng/dL, 25.2% had PAC 5 to 15 ng/dL, and 15.2% had PAC <5 ng/dL, compared with 6%, 12.7%, and 1.6% in the ARR≥20 group and 4.7%, 8.5%, and 0.7% in the ARR≥30 group. CONCLUSIONS: In this cohort of individuals being screened for primary aldosteronism, substantially more individuals were identified using criteria focused on suppression of renin activity compared with using the aldosterone renin ratio as a screening tool.

RESUMEN

Background: The blood pressure (BP)-lowering effect of sacubitril/valsartan (Sac/Val) is greater than that of angiotensin II receptor blockers (ARBs) but in in real-world clinical practice, Sac/Val is used in a variety of patterns other than switching from ARBs. In the present study we investigated the effects of Sac/Val on BP and biochemical parameters when switching from or adding it to various antihypertensive drugs and examined what factors could be predictors of the antihypertensive effect of Sac/Val. Methods and Results: In 108 hypertensive patients treated with antihypertensive agents (including 4 naïve cases), clinic BP and various biochemical parameters were assessed before and after switching to/adding Sac/Val (200 mg/day). Systolic and diastolic BPs significantly decreased after treatment with Sac/Val (P<0.0001, respectively). As for biochemical parameters, alanine aminotransferase, triglycerides, C-reactive protein, and uric acid significantly decreased after administration of Sac/Val, but renal function, B-type natriuretic peptide, and plasma renin activity (PRA) did not change before or after treatment with Sac/Val. Multiple regression analysis revealed that low PRA and high baseline systolic BP were independent determinants of systolic BP reduction after Sac/Val treatment. Conclusions: Sac/Val is beneficial for poorly controlled hypertension in daily clinical practice and low PRA may be a predictor of the antihypertensive effect of switching to/adding Sac/Val.

RESUMEN

Introduction: Low-renin hypertension (LRH) accounts for approximately one-third of patients with hypertension and are more prevalent in women and the older adult population. Previous study has found a link between the renin-angiotensin-aldosterone system (RAAS) and sex hormones. However, there are insufficient data on the relationship between LRH and metabolic or musculoskeletal outcomes in older adults. Methods and materials: Among the 343 participants from a population-based cohort study conducted between May 2018 and August 2019, a total of 256 (86 men older than 50 years and 170 postmenopausal women) were included. The presence of LRH was defined as plasma renin activity (PRA) <1 ng/mL/h and systolic blood pressure (BP) ≥130 or diastolic BP ≥80 mmHg based on the 2017 ACC/AHA guidelines. Individuals with missing data, and those who had used medications that could affect PRA within the past six months were excluded. Bone mineral density (BMD), trabecular bone score (TBS), and appendicular lean mass (ALM) index were assessed using dual-energy X-ray absorptiometry; degraded TBS was defined as partially degraded to degraded levels (≤1.350). Muscle function was assessed according to the Asian Working Group for Sarcopenia guidelines. PRA was measured using radioimmunoassay. Results: The median age was 66 [61-72] years, and the body mass index (BMI) was 24.7 [23.0-26.4] kg/m2. Individuals with LRH, accounting for 34.8%, had lower diabetes mellitus; more dyslipidemia; and poorer muscle function, BMD, and TBS than those in the non-LRH group. In addition, PRA was positively correlated with C-peptide, HOMA-IR, TBS, and ALM index. After adjusting for covariates including age and BMI, LRH was negatively associated with femur neck T-score (adjusted ß = -0.30, 95% CI [-0.55 to -0.05], p = 0.021) and the presence of LRH was significantly associated with degraded TBS in women (adjusted odds ratio = 3.00, 95% CI [1.36-6.58], p = 0.006). Conclusion: Our findings suggest that LRH can influence clinical features and metabolic risk in older adults. Notably, LRH in postmenopausal women was linked to lower femur neck T-scores and degraded TBS, indicating sex-specific effects of LRH on bone health. Larger prospective studies are required to elucidate how changes in the RAAS affect metabolic and musculoskeletal outcomes in older adults.

Asunto(s)

Densidad Ósea , Renina , Masculino , Humanos , Femenino , Anciano , Estudios de Cohortes , Densidad Ósea/fisiología , Absorciometría de Fotón/métodos , República de Corea/epidemiología

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We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB2) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB2 was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.

Asunto(s)

Difenilamina , Histerectomía , Meloxicam , Ovariectomía , Dolor Postoperatorio , Fenilacetatos , Animales , Gatos , Femenino , Analgesia/veterinaria , Analgesia/métodos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Difenilamina/farmacología , Difenilamina/administración & dosificación , Difenilamina/análogos & derivados , Histerectomía/veterinaria , Riñón/efectos de los fármacos , Meloxicam/administración & dosificación , Meloxicam/farmacología , Meloxicam/uso terapéutico , Ovariectomía/veterinaria , Dolor Postoperatorio/veterinaria , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Fenilacetatos/administración & dosificación , Fenilacetatos/farmacología

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INTRODUCTION: Heart failure (HF) progression according to changes in the serum chloride concentration ([sCl-]) was recently proposed as the "chloride (Cl) theory" for HF pathophysiology. The present study examined the association of neurohormones and renal Cl avidity to determine their contribution to acute HF and their involvement to the "Cl theory." METHODS: Data from 29 patients with acute HF (48% men; 80.3 ± 12 years) were analyzed. Blood and urine samples were obtained before decongestive therapy. Clinical tests included peripheral blood, serum and spot urinary electrolytes, b-type natriuretic peptide (BNP), and plasma neurohormones. RESULTS: In the 29 patients, urinary Cl concentrations ([uCl-]) inversely correlated with log (plasma renin activity [PRA]) (r = -0.64, p = 0.0002) and log (plasma aldosterone concentration) (r = -0.50, p = 0.006). The [sCl-]‒[uCl-] difference positively correlated with log PRA (r = 0.63, p = 0.0002) and log (plasma aldosterone concentration) (r = 0.49, p = 0.008). Patients were divided into 2 groups according to the [sCl-]‒[uCl-] difference, an excretion (low renal Cl avidity) group and an absorption (high renal Cl avidity) group. Compared with the excretion group (-77 to ‒5 mEq/L; n = 14), the absorption group (1-84 mEq/L; n = 15) exhibited greater renal impairment (serum creatinine; 1.45 ± 0.63 vs. 1.00 ± 0.38 mg/d, p = 0.029) and cardiac burden (log BNP; 2.99 ± 0.3 vs. 2.66 ± 0.32 pg/mL, p = 0.008), higher log PRA (0.20 ± 0.58 vs. -0.25 ± 0.35 ng/mL/h, p = 0.018), and lower fractional urinary Cl excretion (1.34 ± 1.3 vs. 5.33 ± 4.1%, p < 0.001). CONCLUSION: Renal Cl avidity differs in acute HF, i.e., excretion (low renal Cl avidity) versus absorption (high renal Cl avidity) types, involving renin-aldosterone-angiotensin activity as the underlying mechanism, which provides the neurohormonal background for the "Cl theory." A version of this study was presented in part at the annual international scientific assembly (ACC.23) of the American College of Cardiology, March 4-6, 2023.

Asunto(s)

Aldosterona , Cloruros , Insuficiencia Cardíaca , Riñón , Péptido Natriurético Encefálico , Renina , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/metabolismo , Masculino , Femenino , Cloruros/metabolismo , Cloruros/sangre , Péptido Natriurético Encefálico/sangre , Péptido Natriurético Encefálico/metabolismo , Renina/sangre , Renina/metabolismo , Aldosterona/sangre , Aldosterona/metabolismo , Anciano , Anciano de 80 o más Años , Riñón/fisiopatología , Riñón/metabolismo , Enfermedad Aguda , Neurotransmisores/metabolismo , Sistema Renina-Angiotensina/fisiología

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PURPOSE: To summarize the available data on the prevalence, clinical repercussion, and diagnosis of primary aldosteronism (PA) and to discuss the SPAIN-ALDO registry's findings, which is the largest PA patient registry in Spain. METHODS: A comprehensive review of the literature focused on the prevalence, clinical presentation and diagnosis of PA was performed. RESULTS: PA is the most common cause of secondary arterial hypertension. In addition, PA patients have a higher cardio-metabolic risk than patients with essential arterial hypertension matched by age, sex, and blood pressure levels. However, despite its high prevalence and associated metabolic and cardiovascular complications, PA remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. The diagnostic investigation is a multistep process, including screening, confirmatory testing, and subtype differentiation of unilateral from bilateral PA forms. Data from the SPAIN-ALDO registry have shed light on the cardiometabolic impact of PA and about the limitations in the PA diagnosis of these patients in Spain. CONCLUSIONS: The most common cause of secondary hypertension is PA. One of the most challenging aspects of the diagnosis is the differentiation between unilateral and bilateral PA because adrenal venous sampling is a difficult procedure that should be performed in experienced centers. Data from the SPAIN-ALDO registry have provided important information on the nationwide management of this pathology.

Asunto(s)

Hiperaldosteronismo , Hipertensión , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiología , Aldosterona/metabolismo , España/epidemiología , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/etiología , Presión Sanguínea , Renina

RESUMEN

Background: Previous studies have reported the direct or indirect relationship between the renin-angiotensin-aldosterone system (RAAS) and atrial fibrillation (AF). However, in patients with "apparently" idiopathic AF without possible external influence, whether RAAS is dysregulated at an early stage of AF and its relationship with the recurrence of AF after ablation have not been studied. Methods: This single-center, prospective, case-control study included apparently healthy individuals with AF (the case group) or paroxysmal supraventricular tachycardia (PSVT, the control group) referred for catheter ablation at the same period. The primary outcome was RAAS activation in these two groups. The secondary outcome was the 1-year recurrence of AF after ablation. Results: This study included 51 "apparently" idiopathic AF and 91 patients with PSVT. A greater proportion of patients in the case group had plasma renin activity (PRA) levels < 1 ng/ml/h compared to the control group (25.5 % vs. 7.7 %, P = 0.003). PRA < 1 ng/ml/h was the only factor found to be associated with the diagnose of AF in both the univariate model (odds ratio [OR] 4.11, 95 % confidence interval [CI] 1.52-11.11, P = 0.005) and the model adjusted for age and sex (OR 3.98, 95 % CI 1.20-13.25, P = 0.024). A similar pattern was seen with paroxysmal AF. No significant difference in the components of RAAS was observed between 11 patients with the recurrence of AF and 40 without the recurrence at the 1-year follow-up. Conclusions: This observational study revealed an association between low renin activity and the diagnosis of "apparently" idiopathic AF, particularly paroxysmal AF.

RESUMEN

Background: Paracentesis-induced circulatory disturbance (PICD) occurs in 12-20% of patients receiving human albumin for large-volume paracentesis, and can occur at lower than five liter paracentesis in acute-on-chronic liver failure (ACLF). Albumin infusions are associated with higher costs and more prolonged daycare admissions. The aim of the study was to determine if oral midodrine-hydrochloride can prevent PICD in these patients by increasing the mean arterial pressure (MAP). Methods: This open-labeled randomized controlled trial included ACLF patients undergoing paracentesis between 3 and 5 L, who were randomized to receive either 20% human albumin or midodrine hydrochloride 7.5 mg thrice daily for three days, 2 h before paracentesis. MAP was recorded daily. The primary outcome was the plasma renin activity (PRA) on day six, and a 50% increase from baseline was considered PICD. Results: 183 consecutive patients of ACLF were screened, and 50 patients were randomized to either arms. Alcohol was the most common underlying cause of cirrhosis. On day 6, PRA was non-significantly (P = 0.056) higher in the midodrine group. The absolute change of PRA between the two groups was not significant (P = 0.093). Four (16%) patients in the albumin group and five (20%) in the midodrine group developed PICD. MAP increase was not different between the albumin and midodrine arms (P = 0.851). Midodrine was found to be more cost-effective. Conclusions: Three days of oral midodrine is as effective as a human-albumin infusion in preventing PICD in ACLF patients undergoing paracentesis lesser than that done in large volume paracentesis.

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Background: It is well-accepted that antihypertensive therapy is the cornerstone of treatment for abdominal aortic aneurysm (AAA) patients with hypertension. Direct-acting vasodilators were used in the treatment of hypertension by directly relaxing vascular smooth muscle but may have destructive effects on the aortic wall by activating the renin-angiotensin system axis. Their roles in AAA disease remain to be elucidated. In this study, we used hydralazine and minoxidil, two classical direct-acting vasodilators, to investigate their influence and potential mechanisms on AAA disease. Methods and results: In this study, we investigated the plasma renin level and plasma renin activity in AAA patients. Simultaneously, age and gender ratio-matched patients diagnosed with peripheral artery disease and varicose veins were selected as the control group using a ratio of 1:1:1. Our regression analysis suggested both the plasma renin level and plasma renin activity are positively associated with AAA development. In view of the well-established relationship between direct-acting vasodilators and increased plasma renin concentration, we established a porcine pancreatic elastase-infused AAA mouse model, followed by oral administration of hydralazine (250 mg/L) and minoxidil (120 mg/L) to investigate effects of direct-acting vasodilators on AAA disease. Our results suggested both hydralazine and minoxidil promoted the progression of AAA with increased aortic degeneration. Mechanistically, the vasodilators aggravated aortic inflammation by increased leukocyte infiltration and inflammatory cytokine secretion. Conclusion and relevance: The plasma renin level and plasma renin activity are positively associated with AAA development. Direct vasodilators aggravated experimental AAA progression, which raised cautionary concerns about their applications in AAA disease.

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(1) Background: The renal microcirculation is essential to maintain the renal function, but its determinants in humans have been poorly studied. Contrast-enhanced ultrasound (CEUS) allows the non-invasive quantification of the cortical micro-perfusion at the bedside using the perfusion index (PI). The aims of this study were to assess whether differences exist in PI between healthy males and females and to identify clinical determinants associated with cortical micro-perfusion. (2) Methods: Healthy, normotensive volunteers (eGFR > 60 mL/min/1.73 m2, no albuminuria) underwent CEUS under standardized conditions with the destruction-reperfusion (DR) technique. The mean PI of four DR sequences was reported as the primary outcome measure (3) Results: A total of 115 subjects (77 females and 38 males) completed the study; the mean ± SD age was, respectively, 37.1 ± 12.2 and 37.1 ± 12.7 years in females and males, and the mean eGFR was 105.9 ± 15.1 and 91.0 ± 17.4 mL/min/1.73 m2. The PI (median) was higher in females than in males, i.e., 2705 (IQR 1641-3777) vs. 1965 (IQR 1294-3346) arbitrary units (a.u), p = 0.02). A correlation analysis showed positive associations between PI and eGFR, female sex, heart rate, plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), negative associations with potassium, bicarbonate and systolic blood pressure, and no associations with age, body mass index and renal resistive index (RRI). In a multivariate linear regression analysis, only PRA remained significantly associated with PI. (4) Conclusions: Although the PI was higher among females, this association was no longer significant after adjustment for covariates. There was no difference in females tested during the follicular or the luteal phases. In conclusion, the PI was only weakly influenced by classic clinical variables, but was positively associated with PRA, suggesting that the renin-angiotensin system plays a role in the regulation of the cortical micro-perfusion in humans. Identifying which other factors contribute to the large variations in micro-perfusion across individuals needs further study.

RESUMEN

BACKGROUND: Examination of aldosterone to Renin Ratio (ARR) and plasma aldosterone concentration (PAC) or 24-h urinary aldosterone excretion (24-h UALD) was the necessary tests in confirmatory tests for primary aldosteronism (PA). We developed a combined liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for plasma renin activity (PRA), PAC, and angiotensin II (Ang II) and investigated their reference intervals (RIs) in northern Chinese Han population. The RIs of 24-h UALD excretion were also studied using LC-MS/MS. METHODS: A total of 309 healthy volunteers were recruited in 3 cities in China. PRA, PAC, Ang II, and 24-h UALD were measured using the laboratory-developed LC-MS/MS. Multiple linear regression and the variance component model were applied to determine if the RI needed to be split. The RIs of PRA, PAC, and Ang II were determined using the nonparametric percentile method. RESULTS: The laboratory-developed LC-MS/MS method was verified and showed good performance. Standard deviation ratio (SDR) sex for PAC and SDR region for Ang II are 0.466 and 0.407, respectively, indicating that the RIs of PAC and Ang II must be divided by sex and region, respectively. In addition, the SDR 24hUK for 24-h UALD is 0.579, indicating that the RI of 24-h UALD must be partitioned by urine potassium. CONCLUSION: RIs were established for tests related to the renin-angiotensin-aldosterone system in the apparently healthy northern Chinese Han population by the LC-MS/MS method.

Asunto(s)

Aldosterona , Angiotensina II , Cromatografía Liquida , Sistema Renina-Angiotensina , Renina , Espectrometría de Masas en Tándem , Humanos , Aldosterona/sangre , Aldosterona/orina , Angiotensina II/sangre , Pueblos del Este de Asia , Hiperaldosteronismo , Hipertensión , Hormonas Peptídicas , Renina/sangre , Espectrometría de Masas en Tándem/métodos , Valores de Referencia , Voluntarios Sanos

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Aldosterona , Hipertensión , Humanos , Renina , Hipertensión/tratamiento farmacológico , Potasio

RESUMEN

OBJECTIVE: Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist. DESIGN: We investigated the renin-angiotensin-aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy. METHODS: Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus standard GC therapy (n = 41). MC replacement therapy remained unchanged throughout the study. Blood pressure, serum potassium, serum sodium, plasma renin activity (PRA), and serum 17OHP and androstenedione concentrations were analyzed at baseline, 4, 12, and 24 weeks. RESULTS: The median serum 17OHP in the morning was significantly lower on MR-HC compared with standard GC at 24 weeks (2.5 nmol L-1 (IQR 8.3) versus 10.5 nmol L-1 (IQR 55.2), P = .001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 ng L-1 s-1 (IQR 1.0) to 0.48 ng L-1 s-1 (IQR 0.61), P = .012) but not in patients on standard GC (0.53 ng L-1 s-1 (IQR 0.66) to 0.52 ng L-1 s-1 (IQR 0.78), P = .613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol L-1 to 139.3 ± 1.8 mmol L-1, P = .047), but remained unchanged on standard GC (139.8 ± 1.6 mmol L-1 to 139.3 ± 1.9 mmol L-1, P = .135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels. CONCLUSION: 6 months of MR-HC therapy decreased PRA and increased sodium levels indicating a greater agonist action of the 9α-fluorocortisol dose, which may be due to the decreased levels of the MC-receptor antagonist 17OHP.

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Hiperplasia Suprarrenal Congénita , Hidrocortisona , Humanos , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Renina , Fludrocortisona/uso terapéutico , Glucocorticoides/uso terapéutico , 17-alfa-Hidroxiprogesterona , Potasio , Sodio

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Since the 1970s, when the initial reports of neonatal hypertension related to renal artery thromboembolism were published, other secondary causes of neonatal hypertension have been reported. Those infants with no identifiable cause of hypertension were labeled with a variety of terms. Herein, we describe such infants as having idiopathic neonatal hypertension (INH). Most, but not all, of these hypertensive infants were noted to have bronchopulmonary dysplasia (BPD). More recently, reports described common clinical characteristics seen in INH patients, whether or not they had BPD. This phenotype includes low plasma renin activity, presentation near 40 weeks postmenstrual age, and a favorable response to treatment with spironolactone. A small prospective study in INH patents showed evidence of mineralocorticoid receptor activation due to inhibition of 11ß-HSD2, the enzyme that converts cortisol to the less potent mineralocorticoid-cortisone. Meanwhile, phthalate metabolites have been shown to inhibit 11ß-HSD2 in human microsomes. Premature infants can come in contact with exceptionally large phthalate exposures, especially those infants with BPD. This work describes a common low-renin phenotype, commonly seen in patients categorized as having INH. Further, we review the evidence that hypertension in INH patients with the low-renin phenotype may be mediated by phthalate-associated inhibition of 11ß-HSD2. Lastly, we review the implications of these findings regarding identification, treatment, and prevention of the low-renin hypertension phenotype seen in premature infants categorized as having INH.

Asunto(s)

Hipertensión , Renina , Recién Nacido , Lactante , Humanos , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , Estudios Prospectivos , Hipertensión/etiología , Hipertensión Esencial , Recien Nacido Prematuro , Fenotipo

RESUMEN

BACKGROUND: Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children. METHODS: We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days-2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA). RESULTS: Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3-4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, p < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤2, p < 0.05). CONCLUSIONS: Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter. CLINICAL TRIAL REGISTRATION: The trials are registered on the EU Clinical Trials Register (https://www.clinicaltrialsregister.eu). TRIAL REGISTRATION NUMBERS: EudraCT 2015-002335-17, EudraCT 2015-002396-18.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Cardíaca , Humanos , Recién Nacido , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/uso terapéutico , Enalapril/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Renina/metabolismo , Sistema Renina-Angiotensina , Lactante , Preescolar

RESUMEN

Background: Renal dynamic scans (RDS) despite being considered the gold standard for the diagnosis of pelvic ureteric junction obstruction (PUJO), fail to help resolve the dilemma about management issues in many patients. Multiple invasive and noninvasive methods are being studied to help the decision-making in these patients. We did this study to find correlation of plasma renin activity (PRA) values and resistive index (RI) on Doppler ultrasound with findings of RDS in patients with the Society for Fetal Urology (SFU) Grades 3 and 4 unilateral hydronephrosis (HDN) and also to determine the cut-off values of PRA and RI that could categorically acknowledge the success of pyeloplasty. Methodology: Twenty patients with SFU Grades 3 and 4 unilateral HDN due to PUJO were enrolled. Demographic details were recorded. All underwent Anderson-Hynes dismembered pyeloplasty. Based on the follow-up RDS scans, these patients could fall into one of three categories- improved (successful), status quo, or deteriorated (unsuccessful). Outcomes were compared based on RDS (split renal function [SRF]), ultrasonography, and Doppler findings were done at 3 months of postoperative period. Results: Follow up period was 3 months after Pyeloplasty. Seventeen patients had successful outcomes based on RDS findings, 12 had improvement in SRF (>5%), and 6 had normal drainage curves (t-t1/2<10 min). Three patients had indeterminate curves (t-t1/2between 10 to 20 min). Four had improvement on both the criteria, i.e., SRF and drainage curves. Among the three patients who showed no improvement in RDS, two were in "status quo" category and one patient showed deterioration. Seventeen patients also showed improvement in PRA and RI. No significant correlation between PRA and RI with SRF could be established. However, PRA was found to have good concordance with RDS (90%). Conclusion: No significant correlation could be demonstrated between SRF and the respective values of PRA and RI. However, PRA could act as an adjunct to predict the early success of pyeloplasty in view of good concordance with RDS. A larger trial with bigger cohort of patients is required to confirm our contention.

RESUMEN

INTRODUCTION: The present study examined the possible estimation of plasma renin activity (PRA) by serum and urinary concentrations of chloride versus sodium in acute and chronic heart failure (HF). METHODS: Data from 29 patients with acute HF (48% men; 80.3 ± 12 years) and 26 patients with recovery of HF after decongestive therapy (50% men; 81.2 ± 12 years) were analyzed. Blood and urine samples were obtained immediately before decongestive therapy in acute HF patients. Clinical tests included peripheral blood tests, serum and spot urinary electrolytes, and plasma neurohormones. Sodium- or chloride-related indices included serum ([sNa+] or [sCl-]) and urinary ([uNa+] or [uCl-]) concentrations, their differences, and their ratio. Linear regression analysis was used for correlation coefficients. RESULTS: PRA levels higher than the normal range were detected in only 5 (17%) of 29 patients with acute HF, but in as many as 11 (42%) of 26 patients with chronic HF. In the 29 patients with acute HF, all the chloride- and sodium-related indices except for [sNa+] were correlated with PRA: the [sCl-]/[uCl-] ratio was best correlated with PRA (R2 = 0.84, p < 0.0001) followed by the [sNa+]/[uNa+] ratio (R2 = 0.64, p < 0.0001). In the 26 patients with chronic HF, however, both the [sCl-] (R2 = 0.36, p = 0.001) and [sNa+] (R2 = 0.22, p = 0.016) were only weakly correlated with PRA. CONCLUSION: In acute HF, chloride-related indices derived from serum and urinary concentrations were firmly associated with PRA or better than sodium-related indices. In chronic HF, either chloride- or sodium-related indices were not firmly associated with PRA, presumably due to influence of cardiovascular medication.

Asunto(s)

Insuficiencia Cardíaca , Sodio , Masculino , Humanos , Femenino , Sodio/orina , Renina/uso terapéutico , Cloruros/uso terapéutico , Sistema Renina-Angiotensina