Aldosterone Research Articles

Hyperaldosteronismus

Aldosterone is produced in the adrenal cortex and governs volume and electrolyte homeostasis. Hyperaldosteronism can occur either as primary aldosteronism (renin-independent) or secondary aldosteronism (renin-dependent). As the commonest cause of secondary hypertension, primary aldosteronism is associated with increased cardiovascular risk. Its most prevalent subtypes are aldosterone-producing adenomas as the most frequent unilateral form and bilateral hyperaldosteronism. Unilateral hyperplasia, familial hyperaldosteronism and aldosterone-producing carcinoma are rare. The aldosterone/renin ratio serves as ascreening parameter for primary aldosteronism. If this ratio is elevated, confirmatory testing and adrenal imaging are performed. Adrenal venous sampling is considered the gold standard for the distinction of unilateral from bilateral disease. Unilateral disease can potentially be cured by adrenalectomy, whereas patients that are not candidates for surgery or have bilateral disease are treated with mineralocorticoid receptor antagonists. Over the past 10years, somatic mutations in ion channels or transporters have been identified as causes of aldosterone-producing adenomas and so-called aldosterone-producing cell clusters (potential precursors of adenomas and correlates of bilateral hyperplasia, but also of subclinical hyperaldosteronism). In addition, germline mutations in overlapping genes cause familial hyperaldosteronism. Secondary hyperaldosteronism can occur in patients with hypertension treated with diuretics or in renal artery stenosis.

Endocrine and Electrolyte Balances during Periovulatory Period in Cycling Mares.

Simple SummaryThis study provides new evidence on the physiological mechanisms involved in the electrolyte balance during periovulatory period in cycling mares. The interrelationships among adrenocorticotropic hormone (ACTH), cortisol (CORT), aldosterone (ALD) and electrolytes (sodium—Na+, potassium—K+ and chloride—Cl−) were evaluated. The simultaneous increase in ACTH, CORT and ALD toward the time of ovulation could suggest the involvement of the adrenocortical pituitary axis in the ovulatory mechanisms, contributing at the same time to the maintenance of electrolyte homeostasis.In cycling females, the periovulatory period is characterized by stimulation of the hypothalamic pituitary adrenal (HPA) axis. The aim of present study was to analyze the pattern and interrelationships among adrenocorticotropic hormone (ACTH), cortisol (CORT), aldosterone (ALD) and electrolytes (sodium—Na+, potassium—K+ and chloride—Cl−) during periovulatory period in cycling mares. Venous blood samples were obtained daily from a total of 23 Purebred Spanish broodmares, aged 7.09 ± 2.5 years, from day −5 to day +5 of estrous cycle, considering day 0, the day of ovulation. Plasma ACTH was measured by a fluorescent immunoassay kit, serum CORT and ALD by means of a competitive ELISA immunoassay, and plasma Na+, K+ and Cl− were quantified by an analyzer with selective electrodes for the three ions. ACTH showed higher concentrations at day 0 compared to days −5 to −1 and +1 to +3 (p < 0.05). CORT showed higher concentrations at day 0 compared to days −5 to −2 and +1 to +5 (p < 0.05). ALD showed higher concentrations at day 0 compared to days −5 to −2 (p < 0.05) and +2 (p < 0.05). Na+ and Cl− showed higher concentrations at day 0, compared to day −5 and +5. K+ showed lower concentrations at day 0 compared to day +1 (p < 0.05). The significant correlations obtained between ACTH and CORT (r = 0.20) and between ACTH and ALD (r = 0.32) suggest that although ACTH may have an effect both on CORT and ALD, there are other very important determinants that could be considered. Hence, it is possible to presume that the pituitary adrenocortical response and ALD may be involved in the ovulatory mechanisms without a direct relation with electrolyte pattern.

Relationship of plasma aldosterone levels and carbohydrate metabolism in heart failure with preserved ejection fraction

Aim. To determine the relationship between the blood aldosterone levels and parameters of carbohydrate metabolism in patients with heart failure (HF) with preserved ejection fraction (HFpEF).Material and methods. This cross-sectional study included 158 patients with stable HFpEF. HFpEF was established in the presence of symptoms and/or signs of HF, left ventricular ejection fraction &gt;50%, increased blood NT-proBNP levels, and characteristic structural cardiac changes according to echocardiography. The study did not include patients with primary hyperaldosteronism and those taking mineralocorticoid receptor antagonists within the previous 6 weeks. In all patients, the blood aldosterone and carbohydrate metabolism parameters were assessed. The aldosterone levels were determined by the enzyme immunoassay and the concentration of 40-160 pg/ml was considered the reference values. Diabetes was diagnosed in the following cases: history of diabetes, treatment with antidiabetic drugs, blood glucose level ≥7,0 mmol/L in two samples or glycated hemoglobin (HbA1c) &gt;6,5%. Prediabetes was recorded if the blood glucose level in a patient without diabetes was in the range of ≥5,6 mmol/L and&lt;7,0 mmol/L.Results. In 99 patients (62,7%, group 1), the aldosterone levels were within the normal range, while in the remaining 59 patients (37,3%, group 2), it exceeded the upper limit. Patients with hyperaldosteronemia compared with those with normal aldosterone levels had significantly higher fasting plasma glucose levels (6,60 (6,00-7,90) mmol/L vs 5,80 (5,25-6,80) mmol/L, p&lt;0,001) and HOMA value (5,86±1,12 vs 4,46±1,02, p=0,01). HbA1c levels did not differ significantly between groups. Patients of the 2nd group more often suffered from diabetes (39,0% vs 19,2%, p&lt;0,001) and hyperglycemia in general (89,8% vs 61,6%, p=0,011) compared with patients of the 1st group. Correlation analysis showed a significant relationship between the level of aldosterone and blood glucose (r=0,29), HbA1c (r=0,17) and HOMA (r=0,23) values. After standardization by age, HF class, body mass index, blood pressure, cholesterol and blood potassium levels in multivariate analysis, the presence of hyperaldosteronemia was significantly correlated with diabetes (odds ratio, 1,64, 95% confidence interval, 1,14-3,32, p=0,013) and hyperglycemia (odds ratio, 2,84, 95% confidence interval, 1,94-14,2, p=0,008). Conclusion. The development of secondary hyperaldosteronism in patients with HFpEF is associated with a significant increase in the risk of hyperglycemia and diabetes.

Testing for Primary Aldosteronism in Patients with Treatment-Resistant Hypertension

Approximately one in five hypertensive patients has treatment-resistant hypertension — defined as inadequately controlled blood pressure (BP) with 3

Antifungal therapy with azoles and the syndrome of acquired mineralocorticoid excess

The syndromes of mineralocorticoid excess describe a heterogeneous group of clinical manifestations leading to endocrine hypertension, typically either through direct activation of mineralocorticoid receptors or indirectly by impaired pre-receptor enzymatic regulation or through disturbed renal sodium homeostasis. The phenotypes of these disorders can be caused by inherited gene variants and somatic mutations or may be acquired upon exposures to exogenous substances. Regarding the latter, the symptoms of an acquired mineralocorticoid excess have been reported during treatment with azole antifungal drugs. The current review describes the occurrence of mineralocorticoid excess particularly during the therapy with posaconazole and itraconazole, addresses the underlying mechanisms as well as inter- and intra-individual differences, and proposes a therapeutic drug monitoring strategy for these two azole antifungals. Moreover, other therapeutically used azole antifungals and ongoing efforts to avoid adverse mineralocorticoid effects of azole compounds are shortly discussed.

A Teenager Presents With Hypokalemia and Metabolic Alkalosis

Hypokalemia is one of the most common electrolyte disorders in hospitalized patient. Causes of hypokalemia include impaired renal potassium (K+) excretion, gastrointestinal losses or transcelluar shifts. Assessments of urinary K+excretion, acid-base status, and blood pressure are three major components to the causes ofhypokalemia.A random urine K+-to-creatinine (K+/Cr) less than 13 mEq/g Cr ( 1.5 mEq/mmol indicates primary and secondary hyperaldosteronism, Liddle syndrome, or apparent mineralocorticoid excess. By contrast, in the absence of hypertension, a urine K+ /Cr>1.5, is usually suggestive of surreptitious use of diuretic, Bartter syndrome or Gitelman syndrome. Measurements of the plasma renin activity and plasma aldosterone concentration are necessary to differentiate these conditionsfrom one another.Severe or symptomatic hypokalemia, if not recognized early or treated appropriately can lead to significant mortality and morbidity. In this article the basic principles of normal K+homeostasis and the pathophysiology that can disturb this balance are discussed. A selected case report focusing on the essential aspect of patient’s presentation, signs and laboratory data followed by series of questions with particular attention to the diagnosis and management of hypokalemia needed to assist in the differential diagnosis and treatmentare also discussed.Each question is followed by detailed discussion and reviews the recent publications that are useful at thebedside. Keywords:Hypokalemia; Metaboloc alkalosis; Causes; Diagnoses; Treatment.

Clinical presentation of incidentally discovered adrenal tumors ‒ our experience

Background/Aim. Incidentalomas of the adrenal gland are adrenal masses commonly discovered by chance on imaging not performed for suspected adrenal disease. The aim o f t his study was to analyze clinical, hormonal and histopathological characteristics of adrenal incidentalomas. Methods. This retrospective study included 85 patients (32 men and 53 women) examined for adrenal incidentalomas at the Clinic for Endocrinology, Military Medical Academy in Belgrade, from January 2013 to December 2017. The age of the patients, gender, size, and localization of adrenal tumors, functional activity, as well as the presence of comorbidities were analyzed. Adrenalectomy was performed in 35 patients due to its size and functional activity, and histological findings were analyzed. Results. The largest number (56.4%) of the adrenal tumors, was detected by ultrasound examination of the abdomen, 23 (27.2%) by abdominal computed tomography (CT) scan, 13 (15.2%) by chest CT scan and 1 (1.2%) by magnetic resonance (MR) imaging of the abdomen. The average tumor size was 3.8 ? 2.3 cm (range from 1 to 1 5 c m). Adrenal tumors were bilateral in 20 (23%) patients, in 39 (46%) patients, the tumors were localized in the right adrenal gland, and in 26 (31%) in the left gland. Subclinical hypercortisolism, defined as insufficient cortisol suppression during overnight dexamethasone test (1 mg), was observed in 34 (40%) patients, while the absence of cortisol suppression (autonomous cortisol secretion) was found in 4 (4.7%) patients. In the remaining 47 (55.3%) patients, complete overnight suppression of cortisol secretion was achieved. Thirty-five (41%) patients underwent adrenalectomy; among them, in 4 (11.4%) cases, adrenocortical carcinoma was found, 15 (42.9%) were adenomas, pheochromocytoma was found in 4 (11.4%) cases, nodular hyperplasia in 5 (14.3%) cases, distant metastasis in one (2.8%) case and the remaining were different benign masses. Conclusion. For patients with adrenal incidentalomas, two fundamental questions on determining the functionality of the tumor and/or the presence of malignancy need to be clarified. All patients with adrenal incidentaloma should undergo hormonal evaluation for autonomous or possible autonomous cortisol secretion, as well as for autonomous, adrenergic, and mineralocorticoid excess. In patients with autonomous adrenal secretion, surgery is indicated even if the typical clinical manifestation is absent.

Sekundarni hiperaldosteronizam i hipertenzija

Introduction: Arterial hypertension is a major cardiovascular risk factor affecting about 10-40% of the adult population. Secondary endocrine hypertension most often results from excessive aldosterone secretion. Complications related to excessive aldosterone secretion include atrial fibrillation, myocardial infarction, myocardial fibrosis, left ventricular hypertrophy, stroke, and increased cardiovascular mortality. Case report: This report presents a hypotensive woman with hypertensive reactions, newly diagnosed unilateral hyperplasia of the left adrenal gland and secondary hyperaldosteronism. Due to good blood pressure and normalized electrolyte status as a result of antihypertensive drug therapy and absence of damage to target organs, surgical treatment of unilateral adrenal hyperplasia was postponed. Conclusion: In case of midlife and late-life hypertension, it is necessary to consider a cause in the patient's endocrine system. AUTHORS SUMMARY SRPSKI 2021; 50 (1,2) 51-54

Abnormal neonatal sodium handling in skin precedes hypertension in the SAME rat

We discovered high Na+ and water content in the skin of newborn Sprague–Dawley rats, which reduced ~ 2.5-fold by 7 days of age, indicating rapid changes in extracellular volume (ECV). Equivalent changes in ECV post birth were also observed in C57Bl/6 J mice, with a fourfold reduction over 7 days, to approximately adult levels. This established the generality of increased ECV at birth. We investigated early sodium and water handling in neonates from a second rat strain, Fischer, and an Hsd11b2-knockout rat modelling the syndrome of apparent mineralocorticoid excess (SAME). Despite Hsd11b2−/− animals exhibiting lower skin Na+ and water levels than controls at birth, they retained ~ 30% higher Na+ content in their pelts at the expense of K+ thereafter. Hsd11b2−/− neonates exhibited incipient hypokalaemia from 15 days of age and became increasingly polydipsic and polyuric from weaning. As with adults, they excreted a high proportion of ingested Na+ through the kidney, (56.15 ± 8.21% versus control 34.15 ± 8.23%; n = 4; P < 0.0001), suggesting that changes in nephron electrolyte transporters identified in adults, by RNA-seq analysis, occur by 4 weeks of age. Our data reveal that Na+ imbalance in the Hsd11b2−/− neonate leads to excess Na+ storage in skin and incipient hypokalaemia, which, together with increased, glucocorticoid-induced Na+ uptake in the kidney, then contribute to progressive, volume contracted, salt-sensitive hypertension. Skin Na+ plays an important role in the development of SAME but, equally, may play a key physiological role at birth, supporting post-natal growth, as an innate barrier to infection or as a rudimentary kidney.

Species-specific differences in the inhibition of 11β-hydroxysteroid dehydrogenase 2 by itraconazole and posaconazole

11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) converts active 11β-hydroxyglucocorticoids to their inactive 11-keto forms, thereby preventing inappropriate mineralocorticoid receptor activation by glucocorticoids. Disruption of 11β-HSD2 activity by genetic defects or inhibitors causes the syndrome of apparent mineralocorticoid excess (AME), characterized by hypokalemia, hypernatremia and hypertension. Recently, the azole antifungals itraconazole and posaconazole were identified to potently inhibit human 11β-HSD2, and several case studies described patients with acquired AME. To begin to understand why this adverse drug effect was missed during preclinical investigations, the inhibitory potential of itraconazole, its main metabolite hydroxyitraconazole (OHI) and posaconazole against 11β-HSD2 from human and three commonly used experimental animals was assessed. Whilst human 11β-HSD2 was potently inhibited by all three compounds (IC50 values in the nanomolar range), the rat enzyme was moderately inhibited (1.5- to 6-fold higher IC50 values compared to human), and mouse and zebrafish 11β-HSD2 were very weakly inhibited (IC50 values above 7 μM). Sequence alignment and application of newly generated homology models for human and mouse 11β-HSD2 revealed significant differences in the C-terminal region and the substrate binding pocket. Exchange of the C-terminus and substitution of residues Leu170,Ile172 in mouse 11β-HSD2 by the corresponding residues His170,Glu172 of the human enzyme resulted in a gain of sensitivity to itraconazole and posaconazole, resembling human 11β-HSD2. The results provide an explanation for the observed species-specific 11β-HSD2 inhibition by the studied azole antifungals. The obtained structure-activity relationship information should facilitate future assessments of 11β-HSD2 inhibitors and aid choosing adequate animal models for efficacy and safety studies.

Hyperaldosteronemia as a risk factor of renal dysfunction in patients with heart failure with preserved ejection fraction

Objective: To assess the relationship between plasma aldosterone levels and renal function in patients with heart failure with preserved ejection fraction (HFpEF).Materials and methods: A cross-sectional study included 158 patients with confirmed HFpEF. Patients with primary hyperaldosteronism, edema syndrome, end stage renal disease and taking mineralocorticoid receptor antagonists were excluded. Renal function was assessed by determining daily urinary albumin excretion (UAE) and calculating the glomerular filtration rate (GFR). Plasma aldosterone was measured by enzyme immunoassay.Results: The patients were divided into two groups: 99 patients had normal (40-160 pg/ml) aldosterone plasma level (nAld) and 59 patients had high (&gt; 160 pg/ml) aldosterone level (hAld). hAld patients had significantly higher UAE (median 342 mg/day [interquartile value 253; 453] versus 116 mg/day [32; 255], p &lt; 0.001), and lower GFR (52 ml/min/1.73 m2 [46; 67.5] versus 66 ml/min/1.73 m2 [53; 79]) compared to nAld. The prevalence of impaired renal filtration function and severe albuminuria was higher in hAld group then in nAld (p &lt; 0.001). In binomial logistic regression models adjusted for age, severity of HFpEF and comorbidities high aldosterone plasma level were independent risk factors of significant (&lt; 60 ml/min/1.73 m2) decrease in GFR (odds ratio 4.25, 95% confidence interval 2.01-16.6) and very high (&gt; 300 mg/day) albuminuria (odds ratio 2.23, 95% confidence interval 1.24-9.63).Conclusion: In HFpEF plasma aldosterone levels are closely related to renal function. Secondary hyperaldosteronism is associated with an increased risk of impaired renal filtration and severe albuminuria.

The effect of renin-angiotensin system blockers on aldosterone levels in patients with chronic heart failure with preserved ejection fraction

Objective: to evaluate the effect of renin-angiotensin-aldosterone system (RAAS) blockers on aldosterone level in patients with chronic heart failure with preserved ejection fraction (HFpEF).Materials and methods: the prospective study included 158 patients (58 men and 100 women, mean age 62,3 ± 7,4 years) with HFpEF (&gt; 50 %) and left ventricular diastolic dysfunction. All patients had no history of primary aldosteronism and did not use the mineralocorticoid receptor antagonists during the last 6 weeks. We evaluated the duration of treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-2 receptor antagonists (ARA-2) and its average daily dose. The dose of RAAS blockers was assessed during previous 6 months as a percentage of target. Aldosterone plasma concentration was measured and the normal level was 40 – 160 pg/ml.Results: according to laboratory results 99 patients (62,7 %) had normal aldosterone level (nAld) and 59 patients (37,3 %) had high aldosterone level (hAld). hAld patients had significantly higher duration of RAAS blockers treatment (6 (3; 8) versus 4 (2; 5) years, p &lt; 0,001) and dose (50 (25; 50) % vs 25 (12,5; 50) % of target, р=0,01). Multiple regression analysis showed that after standartization for age, severity of HFpEF, duration of arterial hypertension and comorbidity only long-term (more than 5 years) treatment with RAAS blockers remained the independent risk factor of high aldosterone level (odds ratio 3,16, 95 % confidence interval 2,08 – 8,24).Conclusions: in HFpEF patients’ plasma aldosterone level is closely associated with RAAS blockers treatment. Long-term (more than 5 years) therapy with ACE inhibitors or ARA-2 is the independent risk factor of secondary hyperaldosteronism.

Effects of enzymatically hydrolysed poultry byproduct meal in extruded diets on serum angiotensin-converting enzyme activity and aldosterone in cats

ABSTRACT Several peptides found in hydrolysed poultry byproduct meal can inhibit angiotensin-converting enzyme (ACE) activity, a property that indicates potential antihypertensive and health-promoting effects. This study aimed to assess the effects of extruded diets containing enzymatically hydrolysed poultry byproduct meal (HPM) on cat serum ACE activity and aldosterone (ALD) concentration, nutrient digestibility, and faecal characteristics. On the basis of a preliminary in vitro ACE inhibitory activity assay, a commercial HPM and a commercial conventional poultry byproduct meal (CPM) were selected for further investigation. Two isoenergetic and isonitrogenous diets were formulated: CPM diet (25.7% CPM) and HPM diet (24.7% HPM). In trial 1, the effect of diet on serum ACE activity and ALD concentration was evaluated using 8 healthy cats (4 female and 4 male, 4.1 ± 0.38 kg BW) in a crossover design, with 5 d of adaptation and blood collection on d 6. In trial 2, apparent total tract digestibility and faecal characteristics were evaluated using 12 cats (6 female and 6 male, 4.0 ± 0.72 kg BW) in a completely randomised design. Serum ACE and ALD were analysed using a mixed model, with diet as the fixed effect and cat as the random effect. Data from trial 2 were subjected to analysis of variance, and means were compared by Tukey’s test. In vitro ACE inhibitory activity of HPM (90.4%) was higher than that of CPM (52.0%). Cats fed the HPM diet tended to have lower serum ACE activity than those fed the CPM diet (126 versus 142 U/l, p = 0.09). Serum ALD was not influenced by diet. Diets had similar digestibility values, and faecal consistency scores tended to be higher (firmer faeces) in cats fed the CPM diet than in cats fed the HPM diet (4.6 versus 4.0, p = 0.09). Inclusion of HPM in extruded diets may reduce cat serum ACE activity and promote good faecal consistency without affecting digestibility. Further investigations are needed to explore the potential health benefits of HPM in hypertensive cats.

Reninoma: A Rare Cause of Endocrine Hypertension

Juxtaglomerular tumours are rare causes of secondary hypertension. They typically present with difficult-to-manage hypertension, hypokalemia, hyperreninemia and secondary hyperaldosteronism. The authors describe a clinical case of a 45 years old female patient, with personal history of difficult-to-manage hypertension and hypokalemia since age 35, medicated with four types of anti-hypertensive agents. An analytical study was performed, which revealed secondary hyperaldosteronism [aldosterone 44.3 ng/dL (4 - 28 ng/dL), renin > 1000 mIU/mL (4.4 - 46.2 mIU/mL)]. Abdominal computed tomography scan identified a heterogeneous nodule located in the middle third of the right kidney, with 3.7 cm. Partial nephrectomy was performed and histological analysis confirmed the diagnosis of reninoma. After surgery, the patient had normal levels of aldosterone (9.2 ng/dL) and renin (1.20 mIU/mL), as well as normal blood pressure. The authors want to highlight this potentially curable cause of endocrine hypertension. Surgical resection is the treatment of choice and leads to normalization of blood pressure.

Maxingxiongting mixture attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the rho-kinase signaling pathway.

To explore the mechanism of Maxingxiongting mixture (MXXTM) on pulmonary hypertension in a rat model established by intraperitoneal injection of monocrotaline solution, smoking and forced swimming. A total of 30 male Sprague-Dawley rats were randomly divided into five groups: control group, model group, high-dose of MXXTM group (HM), low-dose of MXXTM group (LM), and fasudil group. The mean pulmonary artery pressure (mPAP) was measured by using a miniature catheter. Lung tissue and right ventricular tissue sections were stained with hematoxylin-eosin. The right ventricle (RV) and left ventricle + septum (LV + S) were weighted. RV/(LV+S) was calculated to reflect the degree of right ventricular hypertrophy. Rho/Rho-kinase signaling pathway key proteins (RhoA, ROCK Ⅰ and ROCK Ⅱ) in rat right ventricular tissue were measured by Western blot analysis. The levels of serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and the levels of plasma renin activity (PRA), angiotensin Ⅱ (ANG-Ⅱ), aldosterone (ALD) in rat anticoagulated plasma were all measured by enzyme-linked immunosorbent assay. Compared with the control group, the mPAP and RV/(LV+S) in the model group were significantly increased. Administration of fasudil resulted in a significant decrease of mPAP and RV/ (LV+S). In the HM group and LM group, mPAP and RV/ (LV+S) were significantly lower than the model group. Compared with the control group, the contents of HIF-1α, VEGF, PRA, ANG-Ⅱ and ALD in the model group were significantly increased. The administration of fasudil and high-dose MXXTM significantly reduced the contents of HIF-1α, VEGF, PRA, ANG-II and ALD. Compared with the control group, the expression of RhoA, ROCK Ⅰ and ROCK Ⅱ in the right ventricle of the model group were significantly increased. The administration of fasudil and high-dose MXXTM significantly reduced the expression of RhoA and Rock Ⅱ proteins. Our results indicated that high-dose of MXXTM had similar effects on reducing pulmonary artery pressure and improving right ventricular remodeling to fasudil. However, MXXTM was unable to restore parameters above to control levels. MXXTM attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the Rho-kinase signaling pathway.

Protective effects of recombinant human brain natriuretic peptide on the myocardial injury induced by acute carbon monoxide poisoning.

To investigate the protective effect of recombinant human brain natriuretic peptide (rhBNP) on myocardial injury after acute carbon monoxide poisoning (ACOP). We retrospectively reviewed medical records of patients with ACOP and high risk of cardiac events admitted to our hospital, and grouped them into rhBNP group and control group according treatments they received. Patients in control group received conventional treatment while those in rhBNP group were treated with rhBNP intravenously for 72 hours on the basis of conventional treatment. Levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), serum creatine kinase MB fraction (CK-MB), aldosterone (ALD), angiotensin II (AT II), and endothelin-1 (ET-1) prior to and after treatment of rhBNP or conventional treatment were collected. Corrected QT dispersion (QTcd) results were calculated based on the electrocardiography data. The left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVS), left ventricular ejection fraction (LVEF), and stroke output (SV) were measured using color Doppler echocardiography. Major adverse cardiovascular events (MACEs) that occurred within 1 month after treatment were recorded. A total of 135 patients in the rhBNP group and 136 patients in the control group were enrolled. Baseline characteristics between the two groups were similar at admission. Levels of cTnI, CK-MB, and ET-1 in the rhBNP group were significantly lower than those in the control group at day 1, 2 and 3 after treatment (P<0.05). Compared with the control group, levels of QTcd, ALD and AT II in the rhBNP group were significantly lower at day 3 after treatment (P<0.05). After 7 days of treatment, the reduction of NT-proBNP in the rhBNP group was significantly greater than that in the control group at each day (P<0.05), and LVEF, SV and LVEDD in the rhBNP group were all greater than those in the control group. After 1 month of treatment, the incidence of MACEs in the rhBNP group was significantly lower than that in the control group. For patients with ACOP and high risk of cardiac events, early treatment of rhBNP can protect injured cardiomyocytes, prevent the injury of carbon monoxide on heart, and reduce the incidence of MACE.

Impaired Distal Tubular Acidification, Renal Cysts and Nephrocalcinosis in Monogenic Hypertension.

Monogenic defects in tubular sodium handling contribute a small proportion to hypertension in childhood. Presentation varies from severe hypertension manifesting at birth to asymptomatic hypertension and hypokalemic metabolic alkalosis detected incidentally in adulthood. A 12-y-old girl presenting with polyuria, polydipsia, severe hypertension and seizures, was found to have hypokalemia, renal medullary cysts and nephrocalcinosis. Clinical exome revealed a homozygous variation of unknown significance in exon 5 of the HSD11B2 gene, indicating the diagnosis of apparent mineralocorticoid excess. Therapy with spironolactone was associated with resolution of hypokalemia and normal blood pressure during two-year follow up.

Diuretic Effect and Metabolomics Analysis of Crude and Salt-Processed Plantaginis Semen.

Plantaginis Semen (PS) is well recognized in traditional Chinese medicine (TCM) and health products. Crude PS (CPS) and salt-processed CPS (SPS) are the two most commonly used decoction pieces of PS, and are included in the 2020 edition of Chinese Pharmacopoeia. Although they all have multiple effects, the mechanisms for treating diseases are different and remain unclear, the processing mechanism of SPS is also indeterminate, which hinders their clinical application to a certain extent. In order to solve these problems and further develop PS in the clinical application. Here, we used saline-loaded model rats for experiments, and utilized an integrated approach consisting of pharmacological methods and metabolomics, which could assess the diuretic impact of CPS and SPS ethanol extracts on saline-loaded rats and elucidate the underlying mechanism. The results showed that CPS and SPS both produced increased urine volume excretion and urine electrolyte excretion, but the levels of aldosterone (ALD) and aquaporin 2 (AQP2) were decreased. And 30 differential metabolites such as linoleic acid, lysoPC(O-18:0), sphingosine-1-phosphate, lysoPC(18:0) were found, mainly involving three metabolic pathways. In conclusion, CPS and SPS both have a diuretic effect, and that of SPS is better. This work investigated the possible diuretic mechanisms of CPS and SPS which may also be the mechanism of PS for anti-hypertension. In addition, a holistic approach provided novel and helpful insights into the underlying processing mechanisms of TCM.

A Potential New Treatment for Diabetic Renal Disease

The mineralocorticoid aldosterone has inflammatory and fibrotic effects on myocardium, which is one reason that the mineralocorticoid-receptor

Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer.

Prostate cancer (PCa) is the commonest non-cutaneous malignancy worldwide and the second cause of cancer death among males in the USA. Approval of the new androgen receptor axis-targeted (ARAT) agents (abiraterone acetate, enzalutamide, apalutamide, and darolutamide) has altered the course of advanced PCa. We aimed to assess the endocrine and metabolic adverse events associated with treatment using ARAT compounds. We searched the PubMed, Cochrane Library, and Scopus databases from database inception to August 2020. We included randomized controlled trials reporting the endocrine and metabolic side effects of ARAT agents compared to each other or to placebo. Although metastatic PCa remains incurable, ARAT medications combined with androgen deprivation therapy improve overall metastasis-free and progression-free survival in metastatic hormone-sensitive PCa, non-metastatic castration-resistant PCa, and metastatic castration-resistant PCa patients. This benefit comes at the cost of certain endocrine and metabolic consequences. Treatment with abiraterone acetate induces mineralocorticoid excess, hypokalemia, hypertension, elevated liver function tests, insulin resistance, and hyperglycemia. Enzalutamide may induce or worsen hypertension and increase the risk of falls and fractures in elderly patients, while common endocrine adverse events of apalutamide include hypothyroidism, hypertension, and skin rash. On the other hand, darolutamide seems to have a somewhat safer endocrine and metabolic profile. Treatment of advanced PCa should be personalized, with administration of a combination of androgen deprivation therapy, ARAT agents, and chemotherapy being based on the patient's safety profile and the risk of side effects.