Aldosterone Activity Research Articles

Are Anxiety and Depression Mediated by Different Mineralocorticoid Receptor Pathways? Results From Primary Aldosteronism

The mineralocorticoid receptor (MR) and its ligand aldosterone play a major role in the pathophysiology of depression. Both could be target of therapeutic interventions. The action of aldosterone is confined to anatomical areas, which co-express MR and the enzyme 11beta-hydroxysteroiddehydrogenase, i.e. the nucleus of the solitary tract.

Mineralocorticoid Receptor Antagonists Eplerenone and Spironolactone Modify Adrenal Cortex Morphology and Physiology.

Mineralocorticoid receptor antagonists (MRAs) are a class of anti-hypertensive drugs that act by blocking aldosterone action. The aim of this study was to evaluate whether the MRAs spironolactone and eplerenone influence adrenal cortical physiology and morphology. Spontaneous hypertensive rats (SHR, n = 18) and normotensive rats (WKY, n = 18) were randomly exposed to a daily dose of spironolactone (n = 6), eplerenone (n = 6), or no drug (n = 6) over 28 days. After that, aldosterone, corticosterone, and 11-deoxycorticosterone plasma concentrations were quantified. Adrenal glands were subjected to morphological analysis to assess lipid droplets content, capsular width, cell proliferation, and steroidogenic proteins expression. The adrenal cortex in untreated SHR showed higher lipid droplet content as than in WKY. In SHR, MRA treatment was associated with higher circulating aldosterone levels and Ki-67 expression in aldosterone-secreting cells. In WKY, the only difference observed after MRA spironolactone treatment was a narrower capsule. There was no difference in abundance of steroidogenic enzyme between groups. In conclusion, MRAs modify adrenal gland function and morphology in SHR. The effects observed within the adrenal glomerulosa with aldosterone-secreting cell proliferation and higher circulating aldosterone levels suggests that MRA treatment provokes activation of the renin angiotensin system. The prognostic value of hyperaldosteronism secondary to MRAs blockade requires further investigation.

Activation of autosomal recessive Pseudohypoaldosteronism1 ENaC with aldosterone

The mineralocorticoid hormone aldosterone stimulates sodium reabsorption in the collecting ducts by increasing the activity of the epithelial sodium channel (ENaC). Being a rate-liming channel the loss of function mutations caused Pseudohypoaldosteronism 1 (PHA1). Despite elevated plasma aldosterone in PHA 1 patients the modulation of PHA 1 causing ENaC mutants with hormone has never been studied. After recording control ENaC current in PHA1 causing ENaC stop codon mutants we demonstrated the activation of aldosterone in the whole cell as well as single channel patch clamp assays. Single channel recoding experiments demonstrated that aldosterone can increase the open probability of all analyzed PHA 1 stop codon mutants and WT. Additionally, we demonstrated by western blot experiments that aldosterone can increase the expression of WT and PHA 1 stop codon mutants. Extensive whole cell patch clamp experiments demonstrated that C-terminal γ ENaC domain is necessary for aldosterone to activate whole cell current in HEK-293 cells. This novel finding of γ ENaC C-terminus dependent activation of whole cell current by aldosterone could alter our understanding of ENaC-mediated sodium reabsorption in the aldosterone-sensitive distal nephron (ASDN).

A HIGH ALDOSTERONE TO RENIN RATIO MEDIATES MICROVASCULAR AND MACROVASCULAR DAMAGE IN NEWLY-DIAGNOSED, TREATMENT-NAÏVE ESSENTIAL HYPERTENSION

Objective: The role of aldosterone in hypertension was generally considered in the context of primary hyperaldosteronism, an uncommon condition (less than 2% in the hypertensive population). However, based on an increased ambulant aldosterone-to-renin ratio (ARR), a marker of inappropriate aldosterone activity, the prevalence of primary hyperaldosteronism in the hypertensive population may be as high as 10% to 15%. There is increasing evidence to suggest a BP-independent effect of aldosterone on left ventricular structure, increased collagen deposition with fibrosis, diastolic dysfunction and arterial stiffness. We hypothesized that aldosterone and renin will be associated with microvascular and macrovascular alterations in never treated essential hypertension. Design and method: We prospectively studied newly diagnosed, untreated essential hypertensive and normotensive subjects (n = 1482, 47% females, mean age 51 ± 0.77, SEM). Pulse wave velocity (PWV), augmentation index (AIx), aortic systolic BP and pulse pressure amplification were measured with applanation tonometry(SphygmoCor). Albumin-creatinine ratio, urine sodium and potassium concentrations were determined from spot urine samples. Laboratory tests included serum creatinine and clearance, plasma renin activity, serum aldosterone, and high-sensitivity C-reactive protein(hs-CRP). Aldosterone to renin ratio(ARR) was divided into tertiles. Results were analysed using JMP Pro(Version 13, SAS for Windows). The patients gave informed consent and the study had Institutional ethics committee permission. Results: The top ARR tertile was associated with the highest levels of brachial BP, aortic systolic BP, AIx, pulse pressure amplification and PWV(P < 0.001 for all). Stepwise regression analysis showed that the positive association between PWV and increasing ARR tertiles remained significant after adjustment for BP, age and other potential confounders(R2 = 0.39, p < 0.05). The top ARR tertile was also associated with high potassium and low sodium urinary excretion, high ACR, low creatinine clearance and high hs-CRP (All p < 0.01). Conclusions: In untreated hypertensive subjects with mild to moderate hypertension, there are significant interactions between ARR and indices of microvascular and macrovascular damage. Our findings indicate that aldosterone and renin adversely modulate microvascular and macrovascular function very early in the evolution of hypertension. While aldosterone antagonism is recommended currently for treatment-resistant hypertension, our findings suggest that it should be initiated early in hypertension.

Associations of excess myocardial mass, echoreflectiveness and aldosterone synthase gene polymorphism in men with hypertension

Hypertensive remodeling of the left ventricle (LV) is largely due to the influence of a number of control genes. In particular, the regulatory gene CYP11B2, which is responsible for the activity of aldosterone in blood plasma, affects the processes of cardiomyocyte hypertrophy, myocardial fibrosis and microcirculation. This study is devoted to the search for the effect of polymorphic aldosterone synthase carriers on the severity of the components of left ventricular hypertrophy in men with essential hypertension (EH) and representatives of the control group, residents of Podyllia region. The aim of the study was to determine associations between excess (inappropriate) myocardial mass, parameters of standard echocardiography and parameters of echoreflectivity in men with essential hypertension, carriers of different polymorphic variants of aldosteronesynthase gene. The study involved 150 men, aged 45-60 years, residents of the Podyllia region, who had no irreversible damage of target organs. Among them, 50 were in the control group, 58 – had EH of 1st stage and 42 men had EH of 2nd stage. All participants were measured for office blood pressure, performed a standard echocardiographic examination with the addition of standard EchoCG protocol by determination of the parameters of echoreflectivity and evaluation of appropriateness of left ventricular l mass (LVM) to hemodynamic load, according to the formula de Simone et al. and calculating the excessiveness ratio (ER) and determined the C-344T polymorphism of the CYP11B2 gene in venous blood samples by PCR. Statistical processing of the obtained results is performed using a specialized statistical application “Statistica 12.0”. It was found that the prevalence of CC polymorphism of the CYP11B2 gene in men with inappropriate LVM was almost twice higher than in men with appropriate to hemodynamic load LVM (p=0.015 by criterion χ2). At the same time, men with inappropriate LVM were characterized by higher values of echoreflectivity parameters BB and mCSV. In contrast to patients of the control group and patients with EH of 1st stage, patients with EH of 2nd stage, actual LVM (287.4 (53.9) g) significantly (p<0.001) exceeded the predicted values (189 (37.8) g). According to the results of Spearman's rank correlation analysis, it was found that the carrier of the CC genotype of aldosterone synthase gene is associated with higher values of the LVM ER. Thus, patients carrying the polymorphic CC variant of CYP11B2 gene are characterized by more pronounced cardiomyocyte hypertrophy, greater excess of LV mass relative to individual hemodynamic needs, more aggressive processes of myocardial fibrosis.

A systematic review and meta-analysis of effects of spironolactone on blood pressure, glucose, lipids, renal function, fibrosis and inflammation in patients with hypertension and diabetes

Purpose Hypertension commonly co-exists with diabetes mellitus (DM), and both are closely related to adverse health outcomes. The activation of aldosterone and mineralocorticoid receptor (MR) may play important roles in this process. Therefore, we aim to evaluate the efficacy of MR antagonists on cardiovascular risk factors, including blood pressure (BP), glucose, lipids, renal function, fibrosis and inflammatory and its safety in patients with both hypertension and DM. Methods We searched PubMed, Embase, Web of Science and Cochrane databases for clinical trials published until December 31, 2019. Studies comparing the effect of spironolactone to placebo in patients with hypertension and DM were included. Mean difference with 95% confidence intervals was used to report outcomes. Results Eleven randomised placebo-controlled trials with 640 participants were finally included with mean follow-up of 5 months. Compared to placebo, spironolactone significantly reduced office systolic (–6.57, 95%CI: −9.21, −3.93) and diastolic BP (–2.63, 95%CI: −4.25, −1.02) as well as ambulatory BP; increased glycosylated haemoglobin by 0.3 but no clear effect on fasting glucose. Spironolactone induced a significantly reduction of urinary albumin but increased serum creatinine (7.60, 95%CI: 4.94, 10.27) and decreased glomerular filtration rate (–4.28, 95%CI: −6.38, −2.18). Markers of fibrosis and inflammation, including NIIINP, PICP, hs-CRP and TNF-α were also decreased after spironolactone therapy. For lipid metabolism, there was no significant difference between groups. Spironolactone mildly increased serum potassium (0.30, 95%CI: 0.23, 0.37). 2.5% subjects treated with spironolactone experienced mild to moderate hyperkalaemia and received medication or dietary advice and another 1.6% developed severe hyperkalaemia and withdrawn from the studies. Conclusion Spironolactone reduced BP and urinary albumin, improve fibrosis and inflammation, whereas slightly increases the glycosylated haemoglobin and serum creatinine in patients with hypertension and diabetes. Long-term RCTs to assess the effects of spironolactone on cardiovascular events in this population are warranted.

Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model

We investigated the role of aldosterone (ALDO) in the development of arterial thrombosis in streptozotocin-induced diabetic rats. To evaluate the effect of endogenous ALDO, the rats underwent adrenalectomy (ADX). ADX reduced the development of arterial thrombosis. A 1 h infusion of ALDO (30 μg/kg/h) enhanced thrombosis in adrenalectomized rats, while this effect was potentiated in diabetic rats. ALDO shortened bleeding time, increased plasma levels of tissue factor (TF) and plasminogen activator inhibitor, decreased plasma level of nitric oxide (NO) metabolites, and increased oxidative stress. Moreover, 2 h incubation of human umbilical vein endothelial cells (HUVECs) with ALDO (10−7 M) disrupted hemostatic balance in endothelial cells in normoglycemia (glucose 5.5 mM), and this effect was more pronounced in hyperglycemia (glucose 30 mM). We demonstrated that the acute ALDO infusion enhances arterial thrombosis in rats and hyperglycemia potentiates this prothrombotic effect. The mechanism of ALDO action was partially mediated by mineralocorticoid (MR) and glucocorticoid (GR) receptors and related to impact of the hormone on primary hemostasis, TF-dependent coagulation cascade, fibrinolysis, NO bioavailability, and oxidative stress balance. Our in vitro study confirmed that ALDO induces prothrombotic phenotype in the endothelium, particularly under hyperglycemic conditions.

Association of Serum Aldosterone and Plasma Renin Activity With Ambulatory Blood Pressure in African Americans: The Jackson Heart Study.

The renin-angiotensin-aldosterone system (RAAS) is an important driver of blood pressure (BP), but the association of the RAAS with ambulatory BP (ABP) and ABP monitoring phenotypes among African Americans has not been assessed. ABP and ABP monitoring phenotypes were assessed in 912 Jackson Heart Study participants with aldosterone and plasma renin activity (PRA). Multivariable linear and logistic regression analyses were used to analyze the association of aldosterone and PRA with clinic, awake, and asleep systolic BP and diastolic BP (DBP) and ABP monitoring phenotypes, adjusting for important confounders. The mean age of participants was 59±11 years and 69% were female. In fully adjusted models, lower log-PRA was associated with higher clinic, awake, and asleep systolic BP and DBP (all P<0.05). A higher log-aldosterone was associated with higher clinic, awake, and asleep DBP (all P<0.05). A 1-unit higher log-PRA was associated with lower odds of daytime hypertension (odds ratio [OR] 0.59 [95% CI, 0.49-0.71]), nocturnal hypertension (OR, 0.68 [95% CI, 0.58-0.79]), daytime and nocturnal hypertension (OR, 0.59 [95% CI, 0.48-0.71]), sustained hypertension (OR, 0.52 [95% CI, 0.39-0.70]), and masked hypertension (OR 0.75 [95% CI, 0.62-0.90]). A 1-unit higher log-aldosterone was associated with higher odds of nocturnal hypertension (OR, 1.38 [95% CI, 1.05-1.81]). Neither PRA nor aldosterone was associated with percent dipping, nondipping BP pattern, or white-coat hypertension. Patterns for aldosterone:renin ratio were similar to patterns for PRA. Suppressed renin activity and higher aldosterone:renin ratios were associated with higher systolic BP and DBP in the office and during the awake and asleep periods as evidenced by ABP monitoring. Higher aldosterone levels were associated with higher DBP, but not systolic BP, in the clinic and during the awake and asleep periods. Further clinical investigation of novel and approved medications that target low renin physiology such as epithelial sodium channel inhibitors and mineralocorticoid receptor antagonists may be paramount in improving hypertension control in African Americans.

Hypertension Editors' Picks: Hyperaldosteronism.

Hypertension Editors' Picks: Hyperaldosteronism.

Pathology of Aldosterone Biosynthesis and its Action.

Aldosterone plays pivotal roles in renin-angiotensin-aldosterone system in order to maintain the equilibrium of liquid volume and electrolyte metabolism. Aldosterone action is mediated by both mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Its excessive actions directly induced tissue injuries in its target organs such as myocardial and vascular fibrosis in addition to chronic kidney diseases. Excessive aldosterone actions were also reported to be involved in unbalanced electrolyte metabolism in inflammatory bowel disease and development of pulmonary diseases. Hyperaldosteronism is tentatively classified into primary and secondary types. Primary aldosteronism is more frequent and has been well known to result in secondary hypertension with subsequent cardiovascular damages. Primary aldosteronism is also further classified into distinctive subtypes and among those, aldosterone-producing adenoma is the most frequent one accounting for the great majority of unilateral primary aldosteronism cases. In bilateral hyperaldosteronism, aldosterone-producing diffuse hyperplasia and aldosterone-producing micronodules or nodules are the major subtypes. All these aldosterone-producing lesions were reported to harbor somatic mutations including KCNJ5, CACNA1D, ATP1A1 and ATP2B3, which were all related to excessive aldosterone production. Among those mutations above, somatic mutation of KCNJ5 is the most frequent in aldosterone-producing adenoma and mostly composed of clear cells harboring abundant aldosterone synthase expression. In contrast, CACNA1D-mutated aldosterone-producing micronodules or aldosterone-producing nodules were frequently detected not only in primary aldosteronism patients but also in the zona glomerulosa of normal adrenal glands, which could eventually lead to an autonomous aldosterone production resulting in normotensive or overt primary aldosteronism, but their details have remained unknown.

Aldosterone is a possible new stimulating factor for promoting vascular calcification.

Background: Aldosterone is an important hormone in the renin-angiotensin-aldosterone system (RAAS), and playing a pivotal role in the development of hypertension, heart failure, and other cardiovascular diseases. Material and method: In this study, the role of the aldosterone in vascular calcification was underwent in rat model compared with other drugs. Vascular calcification, calcium concentration, activity of alkaline phosphatase (ALP), aldosterone, Urotensin II, mineralocorticoid receptor (MR) and Osteopontin (OPN) were detected or confirmed by the von Kossa staining, colorimetric assays, immunohistochemistry and radioimmunoassay, separately. Result: Results revealed that the aldosterone was significantly increased compared calcification + aldosterone group with calcification group, whereas it was notably decreased in calcification + Spironolactone group in the aortic wall. Compared with control group and aldosterone group, calcium content in vascular tissues was increased in calcification group and calcification + aldosterone group. As the immunoreactivity of the MR, OPN, Urotensin II, IL-6, monocyte chemoattractant protein-1, and deposition of collagen in calcification group and aldosterone group, they all were increased slightly, but were significantly increased in calcification + aldosterone group. Conclusion: It is implied that aldosterone may be involved in the development of vascular calcification, however, the mechanism needs to be further studied.

Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone-sensitive HSD2 neurons or sodium appetite.

Restricting dietary sodium promotes sodium appetite in rats. Prolonged sodium restriction increases plasma potassium (pK), and elevated pK is largely responsible for a concurrent increase in aldosterone, which helps promote sodium appetite. In addition to increasing aldosterone, we hypothesized that elevated potassium directly influences the brain to promote sodium appetite. To test this, we restricted dietary potassium in sodium‐deprived rats. Potassium restriction reduced pK and blunted the increase in aldosterone caused by sodium deprivation, but did not prevent sodium appetite or the activation of aldosterone‐sensitive HSD2 neurons. Conversely, supplementing potassium in sodium‐deprived rats increased pK and aldosterone, but did not increase sodium appetite or the activation of HSD2 neurons relative to potassium restriction. Supplementing potassium without sodium deprivation did not significantly increase aldosterone and HSD2 neuronal activation and only modestly increased saline intake. Overall, restricting dietary sodium activated the HSD2 neurons and promoted sodium appetite across a wide range of pK and aldosterone, and saline consumption inactivated the HSD2 neurons despite persistent hyperaldosteronism. In conclusion, elevated potassium is important for increasing aldosterone, but it is neither necessary nor sufficient for activating HSD2 neurons and increasing sodium appetite.

Urinary sodium potassium ratio is associated with clinical success after adrenalectomy in patients with unilateral primary aldosteronism.

Background:The urinary sodium potassium (NaK) ratio is associated with dietary sodium and potassium intake and blood pressure, and it also reflects the activity of aldosterone. Herein we evaluated the value of the urinary NaK ratio in predicting the surgical outcomes of patients with unilateral primary aldosteronism (uPA).Methods:This non-concurrent prospective cohort study was conducted from 2011 to 2017 and included 241 uPA patients who had undergone adrenalectomy. Predictors of successful clinical outcomes were analyzed using logistic regression.Results:Among the 241 uPA patients, 197 (81.7%) achieved clinical complete or partial success. A urinary sodium potassium ratio <3 (odds ratio (OR): 2.5; 95% confidence interval (CI): 1.2–5.4; p = 0.015), body mass index <25 kg/m2 (OR: 2.82; 95% CI: 1.31–6.06; p = 0.008), renin <1 ng/mL/h (OR: 2.51; 95% CI: 1.01–6.21; p = 0.047) and mean preoperative blood pressure >115 mmHg (OR: 5.02; 95% CI: 2.10–11.97; p < 0.001) could predict clinical success after adrenalectomy. Furthermore, higher pre-treatment plasma aldosterone (OR: 1.014; 95% CI 1.005–1.024; p = 0.002) or lower serum potassium (OR: 0.523; 95% CI: 0.328–0.836; p = 0.007) were correlated with lower urinary NaK ratio (<3), and log urinary NaK ratio was positively correlated with serum C-reactive protein (β value 2.326; 95% CI 0.029–4.623; p = 0.047).Conclusions:uPA patients with a lower urinary NaK ratio, due to high plasma aldosterone and low serum potassium concentrations, were more likely to have clinical success after adrenalectomy. uPA patients with a higher urinary NaK ratio were associated with more severe inflammatory status, and possibly more resistant hypertension post-operatively.

Non-coding RNAs and the mineralocorticoid receptor in the kidney

The final steps in the Renin-Angiotensin-Aldosterone signaling System (RAAS) involve binding of the corticosteroid hormone, aldosterone to its mineralocorticoid receptor (MR). The bound MR interacts with response elements to induce or repress the transcription of aldosterone-regulated genes. Along with the classic genomic targets of aldosterone that alter mRNA and protein expression, aldosterone also regulates the expression of non-coding RNAs (ncRNAs). Short ncRNAs termed microRNAs (miRs) have been shown to play a role in transducing aldosterone's actions via MR signaling. The role of miRs in homeostatic regulation of aldosterone signaling, and the potential for aldosterone-regulated miRs to act as feedback regulators of MR have been recently reported. In this review, the role of miRs in RAAS signaling and feedback regulation of MR in kidney epithelial cells will be discussed.

Masked Uncontrolled Hypertension Is Accompanied by Increased Out-of-Clinic Aldosterone Secretion.

Masked uncontrolled hypertension (MUCH) in treated patients is defined as controlled office blood pressure (BP) but uncontrolled out-of-clinic ambulatory BP. Previously, we have shown that patients with MUCH have evidence of heightened out-of-clinic sympathetic nervous system activity. The aim is to test the hypothesis that MUCH patients have higher aldosterone secretion compared with patients with true controlled hypertension. Two hundred twenty-two patients were recruited after having controlled office BP readings at ≥3 clinic visits. Patients taking MR (mineralocorticoid receptor) antagonists and epithelial sodium channel blockers were excluded. All patients were evaluated by clinic automated office BP and morning serum aldosterone and plasma renin activity. Out-of-clinic ambulatory BP monitoring and 24-hour urinary aldosterone, catecholamines, and metanephrines were also measured. Sixty-four patients had MUCH, and the remaining 48 patients had true controlled hypertension. MUCH patients had significantly higher out-of-clinic levels of 24-hour urinary aldosterone, catecholamines, and metanephrines compared with true controlled hypertension. The 2 groups did not differ in serum aldosterone, plasma renin activity, or aldosterone-renin ratio collected in clinic. In addition, 32.8% of MUCH patients had high out-of-clinic 24-hour urinary aldosterone (≥12 µg) but normal clinic serum aldosterone (<15 ng/dL) and aldosterone-renin ratio (<20). Further, in correlation matrix analysis, higher 24-hour urinary catecholamines and metanephrines were associated with higher 24-hour urinary aldosterone and plasma renin activity levels in MUCH patients. Patients with MUCH have higher out-of-clinic urinary aldosterone levels compared with patients with true controlled hypertension. This study suggests that patients with MUCH likely have higher out-of-clinic sympathetic nervous system tone increases aldosterone secretion mediated by increased renin release that may contribute to their higher out-of-clinic BP.

Clinical Evaluation of Assays for Plasma Renin Activity and Aldosterone Measurement by Liquid Chromatography-Tandem Mass Spectrometry.

Aldosterone and renin are pivotal hormones in the regulation of salt and water homeostasis and blood pressure. Measurement of renin and aldosterone in serum/plasma is essential for the investigation of primary hyperaldosteronism (PA) and monitoring of glucocorticoid replacement therapy. We report 2 LC-MS/MS methods developed to measure aldosterone and plasma renin activity (PRA). PRA was determined by endogenous enzymatic generation of angiotensin I using 150 µL of sample. Generated angiotensin I was purified by solid phase extraction prior to chromatographic separation and mass spectrometry. Aldosterone measurement required 300 μL of sample extracted with MTBE prior to LC-MS/MS analysis. The PRA method was linear (1.2-193 nmol/L), sensitive (LLOQ = 1.2 nmol/L), precise (CV = 4.1%), and specific (no cross reactivity for a number of structurally similar steroids). Dilutional linearity and recovery (84%) were acceptable. Accuracy was confirmed by comparison against our current RIA method. The aldosterone method had equally acceptable performance characteristics. Reference ranges in 110 healthy normotensive subjects were: PRA 0.2-3.7 nmol/L/h and aldosterone 50-950 pmol/L. Consecutive patients (n = 62) with adrenal incidentalomas shown to have no functional adrenal disease; their post overnight 1 mg dexamethasone test values were: PRA 0.2-2.6 nmol/L/h and aldosterone 55-480 pmol/L. Serum aldosterone values after 2 liter saline suppression were-normal subjects (n = 17): 78-238 pmol/L and confirmed primary hyperaldosteronism (n = 25): 131-1080 pmol/L. We have developed robust assays for PRA and aldosterone with appropriate clinical evaluation. These assays are now in routine practice in the UK.

Effect of spironolactone on cardiovascular morbidity and mortality in patients with hypertension and glucose metabolism disorders (ESCAM): a study protocol for a pragmatic randomised controlled trial

IntroductionHypertension combined with diabetes and hypokalemia is more likely to develop hyperaldosteronism and is at higher risk of cardiovascular events. There is evidence that activation of aldosterone and mineralocorticoid receptors...

A multi-centre study of neutrophil-to-lymphocyte ratio in primary aldosteronism

BackgroundHypertensive patients with primary aldosteronism (PA) have a higher risk of cardiovascular complications than those with blood pressure–matched essential hypertension. The excess cardiovascular consequences of PA can be attributed to the proinflammatory effect of excessive aldosterone and mineralocorticoid receptor activation in a range of peripheral tissues and cell types. The neutrophil-to-lymphocyte ratio (NLR) is a widely available marker of inflammation which has been shown to predict cardiovascular outcome in the general population. This study aims to evaluate the use of NLR as a potential biomarker of PA and PA severity.MethodsPatients with PA (n = 355) were identified from 2 large PA databases in Australia and China, while controls (n = 222) were patients with hypertension who were referred for assessment but did not meet the diagnostic criteria for PA. The NLR was retrospectively collected from routine full blood examination, prior to commencement of targeted treatment for PA.ResultsThe NLR did not differ between PA patients and hypertensive controls (median 2.3 and 2.4, P = 0.563). However, among patients with PA, the NLR was positively correlated with baseline and post-saline aldosterone levels (r = 0.22 and P < 0.001 for both) and negatively correlated with serum potassium (r = −0.15, P = 0.006). Furthermore, in a logistic regression analysis of data from patients with PA, the NLR predicted the presence of comorbid chronic kidney disease (CKD) (defined as estimated glomerular filtration rate <60 mL/min/1.73m2) with an odds ratio of 1.5 (P = 0.003).ConclusionWhile the NLR did not distinguish PA from controls, it was a marker of PA severity, being associated with aldosterone concentration as well as the presence of CKD. A prospective study is needed to further clarify the role of NLR in predicting end-organ damage associated with PA.

Enfermedades de la secreción de aldosterona

Hyper- and hypoaldosteronism are caused by an excessive or insufficient adrenal secretion of aldosterone, respectively. Idiopathic bilateral hyperplasia and aldosterone-producing adenoma are the commonest causes of primary hyperaldosteronism. Primary hyperaldosteronism is characterized by hypertension, hypokalemia and metabolic alkalosis; in turn, hypoaldosteronism presents hyperkalemia and metabolic acidosis. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test of primary hyperaldosteronism. Functional tests are recommended if ARR is high (salt-loading, intravenous or oral, and fludrocortisone or captopril suppression). Once diagnostic is confirmed, imaging studies (abdominal computed tomography —CT—) and adrenal vein catheterization (in patients for surgery) have to be performed. Plasma levels of aldosterone and renin activity have to be determined by stimulatory functional tests (response to posture and volume depletion tests). Unilateral laparoscopic adrenalectomy is recommended in primary hyperaldosteronism caused by unilateral hyperplasia or adenoma; mineralocorticoid (spironolactone) receptor antagonists are the first-choice treatment for bilateral cases and in patients considered unfit for surgery. Potassium restriction and mineralocorticoid replacement therapy with fludrocortisone is the treatment of hypoaldosteronism.

Mineralocorticoid Receptor Antagonists: a Comprehensive Review of Finerenone.

We aim to review the mechanism of action and safety profile of mineralocorticoid receptor antagonists (MRAs) and discuss the differences between selective and non-selective MRAs. More specifically, finerenone is a new medication that is currently under investigation for its promising cardiovascular and nephrological effects. MRAs are well known for their utility in treating heart failure, refractory hypertension, and diverse nephropathies, namely, diabetic nephropathy. As their name denotes, MRAs inhibit the action of aldosterone at the mineralocorticoid receptor, preventing receptor activation. This prevents remodeling, decreases inflammation, and improves proteinuria. There are not significant differences in outcomes between selective and non-selective MRAs. A new selective MRA named finerenone (originally BAY 94-8862) has shown promising results in several trials (ARTS-HF and ARTS-DN) and smaller studies. Finerenone may have a dose-dependent benefit over older MRAs, decreasing rates of albuminuria and levels of BNP and NT-ProBNP without causing a significant increase in serum potassium levels. This medication is not yet approved as it is still in phase 3 clinical trials (FIGARO-DKD and FIDELIO-DKD trials). MRAs are beneficial in several disease states. Newer medications, such as finerenone, should be considered in patients with heart failure and diabetic nephropathy who may benefit from a reduction in albuminuria and BNP/NT-ProBNP. Data surrounding finerenone are limited to date. However, results from ongoing clinical trials, as well as new trials to evaluate use in other pathologies, could validate the implementation of this medication in daily practice.