Aldosterone Research Articles

Endocrine Hypertension: Overview of Current Understanding

Hypertension is a leading cardiovascular risk factor with significant morbidity and mortality. Sometimes it remains difficult to find out the actual cause and to manage in a large segment of population. So, the ability to identify a contributing or secondary cause that is potentially curable for all patient with hypertension is of great importance and challenging. Endocrine hypertension is one of the common forms of secondary hypertension. Primary aldosteronism, pheochromocytoma, and other causes of mineralocorticoid excess are among the common causes of endocrine hypertension. Published literature were reviewed about their prevalence, clinical presentation, screening methods and specific management. Now day by day it’s become more challenging for the clinicians to understand the pathophysiology, clinical spectrum of these diseases and improvement of the management protocol because of newer clinical, biochemical, and modern radiological approach. Cardiovasc j 2023; 15(2): 159-174

Sodium depletion and secondary hyperaldosteronism in outpatients with an ileostomy: a cross-sectional study

Objective Patients with an ileostomy may experience postoperative electrolyte derangement and dehydration but are presumed to stabilise thereafter. We aimed to investigate the prevalence of sodium depletion in stable outpatients with an ileostomy and applied established methods to estimate their fluid status. Methods We invited 178 patients with an ileostomy through a region-wide Quality-of-Life-survey to undergo outpatient evaluation of their sodium and fluid status. The patients delivered urine and blood samples, had bioelectrical impedance analysis performed and answered a questionnaire regarding dietary habits. Results Out of 178 invitees, 49 patients with an ileostomy were included; 22 patients (45%, 95% CI, 31–59%) had unmeasurably low urinary sodium excretion (<20 mmol/L), indicative of chronic sodium depletion, and 26% (95% CI, 16–41%) had plasma aldosterone levels above the reference value. Patients with unmeasurably low urinary sodium excretion had low estimated glomerular filtration rates (median 76, IQR 63–89, mL/min/1.73m2) and low venous blood plasma CO2 (median 24, IQR 21–26, mmol/L), indicative of chronic renal impairment and metabolic acidosis. Bioelectrical impedance analysis, plasma osmolality, creatinine and sodium values were not informative in determining sodium status in this population. Conclusion A high proportion of patients with an ileostomy may be chronically sodium depleted, indicated by absent urinary sodium excretion, secondary hyperaldosteronism and chronic renal impairment, despite normal standard biochemical tests. Sodium depletion may adversely affect longstanding renal function. Future studies should investigate methods to estimate and monitor fluid status and aim to develop treatments to improve sodium depletion and dehydration in patients with an ileostomy. IMPACT AND PRACTICE RELEVANCE STATEMENT Sodium depletion in otherwise healthy persons with an ileostomy was identified in a few publications from the 1980s. The magnitude of the problem has not been demonstrated before. The present study quantifies the degree of sodium depletion and secondary hyperaldosteronism in this group, and the results may help guide clinicians to optimise treatment. Sodium depletion is easily assessed with a urine sample, and sequelae may possibly be avoided if sodium depletion is detected early and treated. This could ultimately help increase the quality of life in patients with an ileostomy.

Gitelman Syndrome – A Case Report

Hypokalaemia is an electrolyte disorder, commonly encountered in clinical practice. Sometimes, it may present with severe life-threatening complications. We present here a case of 22-year-old female, who was admitted to intensive care unit, for severe hypokalaemia associated with cardiac and neurological complications. She had recurrence of such episodes. On detailed clinical and biochemical evaluation, she was diagnosed to have Gitelman syndrome (GS). She was treated with intravenous potassium and magnesium supplementation under cardiac monitoring and other supportive management. She was discharged in stable condition, on oral supplements, and remained stable on follow-up visits. GS is an autosomal recessive and renal tubular disorder characterised by hypokalaemic metabolic alkalosis with hypomagnesaemia, hypocalciuria, secondary hyperreninemic aldosteronism and hypotension. The disease is caused by biallelic inactivating mutations within the SLC12A3 gene encoding the thiazide-sensitive sodium chloride cotransporter expressed within the apical membrane of cells, lining the distal convoluted tubule. Since GS is an autosomal recessive trait, the recurrence risk for people with an affected child is 25%. It is very important to completely evaluate a patient with hypokalaemia to find the underlying cause. There can be various etiological factors for hypokalaemia ranging from common to rare disorders. If underlying aetiology remains undiagnosed, there may be recurrence as well as increased morbidity and mortality. GS is one such disorder, which needs prompt diagnostic evaluation and treatment.

Artificial intelligence with a deep learning network for the quantification and distinction of functional adrenal tumors based on contrast-enhanced CT images.

Functional adrenal tumors (FATs) are mainly diagnosed by biochemical analysis. Traditional imaging tests have limitations and cannot be used alone to diagnose FATs. In this study, we aimed to establish an artificially intelligent diagnostic model based on computed tomography (CT) images to distinguish different types of FATs. A cohort study of 375 patients diagnosed with hyperaldosteronism (HA), Cushing's syndrome (CS), and pheochromocytoma in our center between March 2015 and June 2020 was conducted. Retrospectively, patients were randomly divided into three data sets: the training set (270 cases), the testing set (60 cases), and the retrospective trial set (45 cases). An artificially intelligent diagnostic model based on CT images was established by transferring data from the training set into the deep learning network. The testing set was then used to evaluate the accuracy of the model compared to that of physicians' judgments. The retrospective trial set was used to evaluate the quantification and distinction performance. The deep learning model achieved an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.915, and the AUCs in all three FAT types were greater than 0.882. The AUC of the model tested on the retrospective dataset reached above 0.849. In the quantitative evaluation of tumor lesion area recognition, the diagnostic model also obtained a segmentation Dice coefficient of 0.69. With the help of the proposed model, clinicians reached 92.5% accuracy in distinguishing FATs, compared to 80.6% accuracy when using only their judgment (P<0.05). The result of our study shows that the diagnostic model based on a deep learning network can distinguish and quantify three common FAT types based on texture features of contrast-enhanced CT images. The model can quantify and distinguish functional tumors without any endocrine tests and can assist clinicians in the diagnostic procedure.

Urinary extracellular vesicles carry valuable hints through mRNA for the understanding of endocrine hypertension.

Urinary extracellular vesicles (uEVs), released from cells of the urogenital tract organs, carry precious information about originating tissues. The study of molecules transported through uEVs such as proteins, lipids and nucleic acids provides a deeper understanding of the function of the kidney, an organ involved in the pathogenesis of hypertension and a target of hypertension-mediated organ damage. Molecules derived from uEVs are often proposed for the study of disease pathophysiology or as possible disease diagnostic and prognostic biomarkers. Analysis of mRNA loading within uEVs may be a unique and readily obtainable way to assess gene expression patterns of renal cells, otherwise achievable only by an invasive biopsy procedure. Interestingly, the only few studies investigating transcriptomics of hypertension-related genes through the analysis of mRNA from uEVs are inherent to mineralocorticoid hypertension. More specifically, it has been observed that perturbation in human endocrine signalling through mineralcorticoid receptors (MR) activation parallels changes of mRNA transcripts in urine supernatant. Furthermore, an increased copy number of uEVs-extracted mRNA transcripts of the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene were detected among subjects affected by apparent mineralocorticoid excess (AME), a hypertension-inducing autosomal recessive disorder due to a defective enzyme function. Moreover, by studying uEVs mRNA, it was observed that the renal sodium chloride cotransporter (NCC) gene expression is modulated under different conditions related to hypertension. Following this perspective, we illustrate here the state of the art and the possible future of uEVs transcriptomics towards a deeper knowledge of hypertension pathophysiology and ultimately more tailored investigational, diagnostic-prognostic approaches.

Age-related Hearing Loss and Aldosterone Treatment

Hearing loss is a common cause of disability in the global population. The prevalence of hearing loss is estimated to dramatically increase in the next decades with an increase in the number of older people. The fact that hearing loss correlates with aging suggests that age-related hearing loss (presbycusis) will be a critical issue and hearing care will be required. Untreated hearing loss has negative effects at multiple levels, such as hearing loss affecting the quality of life of hearing-impaired individuals, deteriorating family relationships, and interfering with economic growth. Unfortunately, treatments for hearing loss are limited to the use of hearing devices. Studies have shown that the number of hearing aid users is approximately 20% of all hearing-impaired individuals. Therefore, having alternative treatments is critical to reduce the number of people with hearing loss and to prevent a dramatic increase in the number of hearing-impaired individuals. In the future, a potential medication may be aldosterone (ALD). Studies have reported positive effects of ALD treatments on hearing loss in aged mice. ALD treatment in aged mice shows an improvement in hearing sensitivity and a healthier cochlear structure. Although higher ALD concentrations are associated with better hearing sensitivity and hearing in noise ability than lower concentrations, there is no clinical trial in ALD treatment in human has been reported.

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

IN THE PRACTICE OF AN ENDOCRINOLOGIST: A CLINICAL CASE

The article presents a clinical case of secondary hyperaldosteronism in a patient with gouty and diabetic nephropathy. A number of diagnostic procedures are described to differentiate secondary hyperaldosteronism from primary hyperaldosteronism.

Phase 1/2a study of PRL-02, a long-acting intramuscular (IM) depot injection of abiraterone decanoate in patients (pts) with advanced prostate cancer.

141 Background: PRL-02 (abiraterone decanoate) is a novel, long-acting IM depot prodrug of abiraterone. In non-clinical models, PRL-02 provided high and durable concentrations of prodrug and abiraterone to target tissues including adrenal glands, lymph nodes and bone. Single doses of PRL-02 suppressed testosterone (T) through 14 weeks in a castrate monkey model to concentrations comparable to oral abiraterone acetate (AA) with lower and less variable plasma abiraterone exposures. Clinically, PRL-02 blocks androgens with minimal increases in mineralocorticoids or depletion of glucocorticoids via inhibition of CYP17 lyase and minimal inhibition of CYP17 hydroxylase. PRL-02 has the potential for a superior therapeutic index and safety profile compared to oral AA. Methods: Phase 1 is a standard 3+3 design intended to identify a recommended phase 2 dose (RP2D). Pts with metastatic castrate resistant or sensitive prostate cancer (mCRPC/mCSPC) and a screening T of 2 - 50 ng/dL were administered IM PRL-02 every 12 weeks with daily oral dexamethasone. Results: As of 8Sep22, 17 pts (6 mCRPC, 11 mCSPC) were treated across 5 dose cohorts (180, 360, 720, 1260, 1800mg). Generally, there was a dose-proportional increase in abiraterone concentrations following a single dose of PRL-02 with a Tmax of 14 - 28 days and a plasma half-life of 18.3 days. The median baseline T level was 7.45ng/dL. Among pts dosed at 720mg and above, 9 of 11 had a 90% reduction in T or values ≤ 1ng/dL at day 28, including 2 pts with T≤LLOQ of 0.1 ng/dL, and PSA50 responses were observed in 8 of 10 with post-baseline results. There were no treatment related serious adverse events (AEs) or dose limiting toxicities. G3 AEs related to PRL-02 included hip and shoulder pain. G2 related AEs included fatigue, decreased appetite, insomnia and hot flush; symptoms of mineralocorticoid excess were not reported. Minimal and transient changes in ‘up-stream’ steroids (e.g., progesterone (P) and corticosterone (C)) were observed through the 1800mg dose. Although serial radiology was not prospectively required, there was radiographic improvement in 6 pts with data available. Conclusions: PRL-02 was well tolerated. Dose-dependent T suppression was associated with clinical benefit including PSA responses and radiographic improvement. Based on a historical comparison, the levels of P and C are significantly lower than seen with AA + prednisone which appear to be due to greater CYP17 lyase selectivity. The 1260mg or 1800mg dose will be the RP2D. Clinical trial information: NCT04729114 . [Table: see text]

Effects of Long-Term Intervention with Losartan, Aspirin and Atorvastatin on Vascular Remodeling in Juvenile Spontaneously Hypertensive Rats

Hypertension in adolescents is associated with adverse cardiac and vascular events. In addition to lowering blood pressure, it is not clear whether pharmacological therapy in early life can improve vascular remodeling. This study aimed to evaluate the effects of long-term administration of losartan, aspirin, and atorvastatin on vascular remodeling in juvenile spontaneously hypertensive rats (SHRs). Losartan, aspirin, and atorvastatin were administered via gavage at doses of 20, 10, and 10 mg/kg/day, respectively, on SHRs aged 6-22 weeks. Paraffin sections of the blood vessels were stained with hematoxylin-eosin (H&E) and Sirius Red to evaluate the changes in the vascular structure and the accumulation of different types of collagen. The plasma levels of renin, angiotensin II (Ang II), aldosterone (ALD), endothelin-1 (ET-1), interleukin-6 (IL-6), and neutrophil elastase (NE) were determined using ELISA kits. After the 16-week treatment with losartan, aspirin, and atorvastatin, the wall thickness of the thoracic aorta and carotid artery decreased. The integrity of the elastic fibers in the tunica media was maintained in an orderly manner, and collagen deposition in the adventitia was retarded. The plasma levels of renin, ALD, ET-1, IL-6, and NE in the SHRs also decreased. These findings suggest that losartan, aspirin, and atorvastatin could improve vascular remodeling beyond their antihypertensive, anti-inflammatory, and lipid-lowering effects. Many aspects of the protection provided by pharmacological therapy are important for the prevention of cardiovascular diseases in adults and older adults.

Urine sodium excretion is related to extracellular water volume but not to blood pressure in 510 normotensive and never-treated hypertensive subjects

Purpose High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. Materials and methods Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. Results The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4–44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p = .003), and 24-h Na+ excretion was not related with extracellular water volume. Conclusion In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.

Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay

Screening for possible interferences from steroidal compounds other than the target analytes (endogenous or exogenous) is well established in LC-MS/MS assay development for steroid quantification in a routine clinical setting. However, interferences from non-steroidal substances have, hitherto, not been explored. After screening more than 150 pharmaceuticals and their metabolites by analyzing commercial quality control samples from TDM analysis kits (Recipe, Chromsystems) with a multisteroid LC-MS/MS assay (protein precipitation followed by HybridSPE filtration, biphenyl column, methanol-water gradient with NH4F additive), we can report the finding of two newly discovered potential interferences from non-steroidal drugs. Antidepressant paroxetine (PX) was identified as an interference to 17-hydroxyprogesterone (17P), and α-hydroxytriazolam (α-OH-TZM)-a major metabolite of benzodiazepine triazolam (TZM)-was identified as an interference to aldosterone (ALDO). Despite different elemental and structural compositions and nominal masses, the M+1 isotopologues of PX and α-OH-TZM produced overlapping signals in ion traces monitored for the respective analytes (m/z 331 → 109/97 and 361→315/343, respectively). PX and TZM are frequently prescribed drugs, and their therapeutic ranges are far exceeding the reference ranges of 17P or ALDO (µmol vs nmol); therefore, these interferences should be considered clinically relevant. Striving for faster multi-analyte methods with high sample turnover, especially in the field of steroid quantification, can limit assay selectivity and specificity. Therefore, supported by the findings of this study, screening for potential interferences in multi-analyte LC-MS/MS method development should not cover only substances of the same class but also include a set of common drugs.

Lysine specific demethylase 1 deficiency modifies aldosterone synthesis in a sex-specific manner.

Biologic sex influences the development of cardiovascular disease and modifies aldosterone (ALDO) and blood pressure (BP) phenotypes: females secrete more ALDO, and their adrenal glomerulosa cell is more sensitive to stimulation. Lysine-specific demethylase 1 (LSD1) variants in Africans and LSD1 deficiency in mice associate with BP and/or ALDO phenotypes. This study, in 18- and 40-week-old wild type (WT) and LSD1+/- mice, was designed to determine whether: 1) sex modifies ALDO biosynthetic enzymes; 2) LSD1 deficiency disrupts the effect of sex on these enzymes; 3) within each genotype, there is a positive relationship between ALDO biosynthesis (proximate phenotype), plasma ALDO (intermediate phenotype) and BP levels (distant phenotype); and 4) sex and LSD1 genotype interact on these phenotypes. In WT mice, female sex increases the expression of early enzymes in ALDO biosynthesis, but not ALDO levels or SBP. However, enzyme expressions are shifted downward in LSD1+/- females vs. males, so that early enzyme levels are similar but the late enzymes are substantially lower. In both age groups, LSD1 deficiency modifies the adrenal enzyme expressions, circulating ALDO levels and SBP in a sex specific manner. Finally, significant sex/LSD1 genotype interactions modulate the three phenotypes in mice. In conclusion, biologic sex in mice interacts with LSD1 deficiency to modify several phenotypes: 1) proximal (ALDO biosynthetic enzymes); 2) intermediate (circulating ALDO); and 3) distant (SBP). These results provide entrée to better understand the roles of biologic sex and LSD1 in: 1) hypertension heterogeneity and 2) in providing more personalized treatment.

Correlative study on retinal microvascular changes and sex hormones in male patients with central serous chorioretinopathy

Central serous chorioretinopathy (CSC) is a disease in which the outer retinal barrier is damaged with high incidence in young adult males. We aimed to analyze the correlations between retinal microvascular changes and sex hormone levels. The vascular density of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP), foveal avascular zone (FAZ) area, choriocapillary blood flow area, and the subfoveal choroidal thickness (SCT) were investigated by optical coherence tomography angiography (OCTA). We also determined the levels of sex hormones (adrenaline (AD), norepinephrine (NE), dopamine (DA), corticosteroids (Cor), aldosterone (ALD), estradiol (E2) and total testosterone (TT)). The relationship between sex hormone levels and OCTA parameters was then determined. We detected significantly higher levels of NE, Cor and TT in serum from the observation group than in the control group (p &lt; 0.05). Significant correlations were identified between SCT and choriocapillary blood flow area in the affected eyes, contralateral eyes and healthy eyes in the control group (p &lt; 0.05). SCT levels of both eyes in the observation group were higher and the choriocapillary blood flow area was smaller than in the control group. The SCT in affected eyes from the observation group were higher than the contralateral eyes (p &lt; 0.05). The choriocapillary blood flow area was significantly smaller than in the contralateral eyes (p &lt; 0.05). Correlation analysis unveiled that NE, Cor and TT levels were positively correlated with SCT in CSC patients and negatively correlated with choriocapillary blood flow area (p &lt; 0.05). The serum levels of sex hormone levels in male CSC patients were different from those in healthy men of the same age. Our findings suggest that the serum levels of NE, Cor and TT levels may influence the pathogenesis of CSC by affecting SCT thickness and choriocapillary blood flow.

Post-Hypercapnic Alkalosis: A Brief Review.

Metabolic alkalosis is a common acid-base imbalance frequently observed in intensive care unit (ICU) patients and is associated with increased mortality. Post-hypercarbia alkalosis (PHA) is a type of metabolic alkalosis caused by sustained high serum bicarbonate levels following a rapid resolution of hypoventilation in patients with chronic hypercapnia due to prolonged respiratory disturbance. Common causes of chronic hypercapnia include chronic obstructive pulmonary disease (COPD), central nervous system disorders, neuromuscular disorders, and narcotic abuse. Rapid correction of hypercapnia through hyperventilation leads to a swift normalization of pCO2, which lacks renal compensation, consequently causing an increase in plasma HCO3- levels and severe metabolic alkalosis. Most of PHA occurs in the ICU setting requiring mechanical ventilation and can progress severe alkalemia due to secondary mineralocorticoid excess from volume depletion or decreased HCO3- excretion from decreased glomerular filtration rate and increased proximal tubular reabsorption. PHA is associated with increased ICU stay, ventilator dependency, and mortality. Acetazolamide, a carbonic anhydrase inhibitor, has been utilized for managing PHA by inducing alkaline diuresis and reducing tubular reabsorption of bicarbonate. While acetazolamide effectively improves alkalemia, its impact on hard outcomes may be limited by factors such as patient complexity, co-administered medications, and underlying conditions contributing to alkalosis.

In vitro methods to assess 11β-hydroxysteroid dehydrogenase type 2 activity.

11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) converts active 11β-hydroxyglucocorticoids to their inactive 11-keto forms, fine-tuning the activation of mineralocorticoid and glucocorticoid receptors. 11β-HSD2 is expressed in mineralocorticoid target tissues such as renal distal tubules and cortical collecting ducts, and distal colon, but also in placenta where it acts as a barrier to reduce the amount of maternal glucocorticoids that reach the fetus. Disruption of 11β-HSD2 activity by genetic defects or inhibitors causes the syndrome of apparent mineralocorticoid excess (AME), characterized by hypernatremia, hypokalemia and hypertension. Secondary hypertension due to 11β-HSD2 inhibition has been observed upon consumption of excessive amounts of licorice and in patients treated with the azole fungicides posaconazole and itraconazole. Furthermore, inhibition of 11β-HSD2 during pregnancy with elevated exposure of the fetus to cortisol can cause neurological complications with a lower intelligence quotient, higher odds of attention deficit and hyperactivity disorder as well as metabolic reprogramming with an increased risk of cardio-metabolic disease in adulthood. This chapter describes in vitro methods for the determination of 11β-HSD2 activity that can be applied to identify inhibitors that may cause secondary hypertension and characterize the enzyme's activity in disease models. The included decision tree and the list of methods with their advantages and disadvantages aim to enable the reader to select and apply an in vitro method suitable for the scientific question and the equipment available in the respective laboratory.

JS-NG-10: A RARE CAUSE OF TREATMENT-RESISTANT HYPERTENSION

Objective: To present an educational case report. Design and method: In a 22-year old female arterial hypertension was diagnosed and she was treated to blood pressure target values with a combination of candesartan and lercanidipine. At the age of 27 years she planned a pregnancy, therefore antihypertensive treatment was switched to alpha-methyl-dopa and metoprolol. Blood pressure control was no longer achieved, the patient was symptomatic, mostly headaches. A diagnostic work-up for secondary causes of hypertension was performed. Results: There were no signs of kidney disease, renal artery stenosis was ruled out by color-coded duplex-ultrasound, plasma metanephrines were normal, sleep apnea syndrome and hypercortisolism were clinically very unlikely and not formally ruled out. No signs of hypertensive end-organ damage (left ventricular hypertrophy, microalbuminuria, carotid artery alterations) were detected. The only pathologic finding confirmed was a marked secondary hyperaldosteronism. Plasma renin concentration was 230 pg/ml, plasma aldosterone concentration 508 pg/ml, along with low normal serum potassium (3.5 to 4 mmol/l). Addition of nifedipine and low-dose HCT did not achieve blood pressure control, daytime ABPM mean was 144/102 mmHg, nighttime ABPM mean 127/86 mmHg. Because of suspected missed renal artery stenosis (fibromuscular dysplasia) an MR-angiography of the renal arteries was performed revealing normal renal arteries and normal adrenal glands but a left kidney tumor - not observed in the previous ultrasound examination but confirmed with contrast-enhanced ultrasound. Surgical removal of the tumor was performed. The histology was suggestive for a juxtaglomerular cell tumor (reninoma). After surgery, plasma aldosterone normalized to 57 pg/ml and plasma renin concentrations were low (3.4 pg/ml). Within 3 months after surgery, all antihypertensive medication could be discontinued and home blood pressure measurements averaged 119/78 mmHg. Soon thereafter the patient became pregnant and delivered a healthy girl. There were no pregnancy related complications and the patient remained normotensive. A juxtaglomerular cell tumor represents a rare curable cause of hypertension. The first report dates for 1967, until 2019 only about 100 cases were reported in the literature. It may be suspected that the diagnosis juxtaglomerular cell tumors is missed in many cases since these tumors are not easy to detect in standard diagnostic workup of hypertension and many antihypertensive drugs interfere with plasma renin concentrations.

PS-BPR02-4: RENOVASCULAR HYPERTENSION FROM FIBROMUSCULAR DYSPLASIA WITHOUT ABNORMALITIES IN RENAL DOPPLER ULTRASOUND: A CASE REPORT.

Background: Renovascular hypertension (RVH) is one of the most common forms of secondary hypertension, and accounts for nearly 1% of all hypertension cases. It is characterized by compromised renal perfusion pressure, resultant renin secretion, and hypokalemia due to secondary hyperaldosteronism. Arteriosclerosis is a common underlying pathogenesis in middle-aged and older adults, whilst fibromuscular dysplasia is occasionally seen in younger patients with RVH. Since cardiovascular complications are of grave concern in RVH, early detection and appropriate therapeutic intervention are particularly important. Here, we report a case of renovascular hypertension from fibromuscular dysplasia which was incidentally unveiled during close examination of an adrenal tumor. Case report: A 55-year-old woman was being treated for hypertension by her primary care physician. She was referred to our hospital for a thorough examination of her right ureteral stone, which necessitated a CT scan incidentally revealing an left adrenal nodule measuring 8 mm in size. Primary aldosteronism was unlikely based on the lack of renin suppression (active renin concentration, 36.5 pg/mL; plasma aldosterone levels, 263 pg/mL and aldosterone-renin ratio &lt; 40 under treatment with nifedipine 40 mg/day. Ultrasound of the kidney demonstrated a notable difference in size between the right and left kidneys of 87 mm and 106 mm, respectively, albeit Renal Artery Doppler failed to suggest the renal artery stenosis. CT scan with contrast material revealed the remarkable irregularity and “string on beads” sign on the distal main trunk of the right renal artery. Renovascular hypertension from fibromyalgia dysplasia was suspected, and percutaneous renal artery angioplasty was performed. After the pressure gradient across the stenotic lesion (105/99 mmHg on the distal side and 125/67 mmHg on the proximal side of the renal artery) was verified, balloon dilation was applied. The procedure was successful as the pressure gradient virtually resolved (105/95 mmHg on the distal side and 109/101 mmHg on the proximal side of the renal artery). Digital subtraction angiography indeed reaffirmed improvement in blood flow. Conclusion: Renovascular hypertension can go unnoticed solely based on renal Doppler Ultrasound. This was a case in which renovascular hypertension from fibromuscular dysplasia was incidentally identified in CT scan designated as a work-up for an adrenal tumor.

Obstructive and secretory complications of diverting ileostomy

This review aimed to highlight the etiology, diagnosis, treatment, and prevention of obstructive and secretory complications associated with diverting ileostomy (DI). Obstructive complications at the stoma site are termed stoma outlet obstruction (SOO) or stoma-related obstruction (SRO). The incidence of SOO/SRO is 5.4%-27.3%, and the risk factors are multifactorial; however, the configuration of the stoma limb and the thickness of the rectus abdominis muscle (RAM) may be of particular concern. Trans-stomal tube decompression is initially attempted with a success rate of 33%-86%. A thick RAM may carry the risk of recurrence. Surgical refinement, including a wider incision of the anterior sheath and adequate stoma limb length, avoids tension and immobility and may decrease SOO/SRO. Secretory complications of DI are termed high output stoma (HOS). Persistent HOS lead to water and sodium depletion, and secondary hyperaldosteronism, resulting in electrolyte imbalances, such as hypomagnesemia. The incidence of HOS is 14%-24%, with an output of 1000-2000 mL/d lasting up to three days. Treatment of HOS is commenced after excluding postoperative complications or enteritis and includes fluid intake restriction, antimotility and antisecretory drug therapies, and magnesium supplementation. Intensive monitoring and surveillance programs have been successful in decreasing readmissions for dehydration.

Exosome‑encapsulated miR‑26a attenuates aldosterone‑induced tubulointerstitial fibrosis by inhibiting the CTGF/SMAD3 signaling pathway.

Renal tubulointerstitial fibrosis (TIF) is a hallmark in the continuous progression of chronic kidney disease (CKD), in which excessive activation of the renin‑angiotensin‑-aldosterone system serves a crucial role. Currently, there are no targeted therapies for the progression of TIF. microRNA (miR)‑26a may be an ideal anti‑fibrosis candidate molecule; however, the effect of miR‑26 on aldosterone (ALD)‑induced TIF remains unclear. This study aimed to elucidate the role of miR‑26a in ALD‑induced TIF. In the present study, we hypothesized that delivery of miR‑26a by exosomes could attenuate ALD‑induced TIF. miR‑26a expression was downregulated in the kidney of ALD‑induced mice compared with the mice in the sham group. Exosome‑encapsulated miR‑26a (Exo‑miR‑26a) was manufactured and injected into ALD‑treated mice through the tail vein. Invivo experiments showed that Exo‑miR‑26a alleviated the downregulated miR‑26a expression in the kidney, tubular injury and ALD‑induced TIF, which was determined using Masson's trichrome staining and assessment of lipocalin 2, α‑smooth muscle actin, collagenI and fibronectin expression. Moreover, invitro experiments revealed that Exo‑miR‑26a inhibited epithelial‑mesenchymal transition and extracellular matrix deposition in mouse tubular epithelial cells. Mechanistically, overexpressing miR‑26a led to decreased expression levels of connective tissue growth factor by directly binding to its 3'‑UTR and inhibiting the activation of SMAD3. These findings demonstrated that the exosomal delivery of miR‑26a may alleviate ALD‑induced TIF, which may provide new insights into the treatment of CKD.