Renin Activity Research Articles

Abstract 102: Targeted Disruption Of Ctcf Binding Near The Ren Gene Alters Local Gene Expression In Response To Dietary Salt

Blood pressure regulation and hypertension risk may be impacted by changes in chromatin conformation (CC) caused by common genetic variations. CCCTCF-binding factor (CTCF) is a DNA architecture protein that regulates CC and thereby gene expression. We hypothesized that disruption of local CC surrounding the renin gene can alter local gene expression and influence blood pressure changes to dietary salt. Three mutant rat models were created using CRISPR-Cas9 in the Dahl salt-sensitive rat with mutations in one or more CTCF motifs surrounding the renin gene. Disruption of CTCF binding was confirmed at specific mutated sites in all three models. Plasma renin activity (PRA) was measured and RNA-seq analysis was performed in multiple tissues of wild-type (WT) and mutant rats fed a 0.1%, 0.4% or 4.0% NaCl diet for four days. While PRA in WT males responded as expected (17.52±0.81, 12.87±1.00, and 7.13±0.19 ng/mL; p<0.05 for 0.1% and 4.0% vs. 0.4%) on these diets respectively, males from two of three mutant strains failed to increase their PRA on 0.1% NaCl diet. Females were unaffected. At the transcriptional level in kidney cortex, one mutant strain failed to increase renin mRNA expression on 0.1% NaCl diet, while another did not decrease expression on 4.0% NaCl diet. Other local genes Kiss1 and Snrpe were also significantly disrupted in kidney cortex. Renin expression was also disrupted in liver and adrenal gland in two of three mutant strains. Blood pressure and urinary protein excretion were measured in CTCF mutant and WT littermates over the course of 28 days at baseline (3 days, 0.4% NaCl diet), followed by seven days on 0.1% NaCl, then 21 days 4.0% NaCl diet. While no significant effects were observed between WT and mutant males or females on 0.4% or 0.1% NaCl diet, mean arterial pressure response to 4.0% NaCl diet was significantly attenuated in females of one of three mutant strains on days 16, 17 and 20 (169.6±7.09 vs. 144.2±2.69 mmHg at Day 20; p<0.005). No changes in urinary albumin or protein excretion in mutants of either sex were detected. Collectively, these data suggest that disruption of CTCF binding around the renin gene alters PRA and local gene expression in multiple tissues in response to dietary salt.

Elevated Blood Pressure and Aldosterone Dysregulation in Young Black Women Versus White Women on Controlled Sodium Diets.

Black women have a higher prevalence of hypertension as compared to White women. Differences in dietary sodium intake have been implicated as a contributing factor for the disparities in hypertension. Our objective was to understand whether young Black women would have higher systolic blood pressure (SBP) than White women even on controlled sodium diets and to determine whether SBP differences were due to differences in dietary sodium intake and/or aldosterone regulation. The analyses included 525 hypertensive and normotensive women (ages 18-71) from the International Hypertensive Pathotype consortium, who were maintained on liberal sodium (LIB; >200 mEq sodium/day) and restricted sodium (RES; 10 mEq sodium/day) diets. Multivariate regression analyses (adjusted for age, race, study site, body mass index) found that Black women (ages 18-50) had significantly higher SBP than White women on both sodium diets: +8.7 ± 2.7 mmHg (P-value = .002) on a LIB diet and +8.5 ± 2.5 mmHg (P-value = .001) on a RES diet. Even among 18- to 35-year-olds-who were normotensive and nonobese-Black women had higher SBP: +7.9 ± 2.4 mmHg (P-value = .001) on a LIB diet and +7.6 ± 2.7 mmHg (P-value = .005) on a RES diet. Younger Black women also had higher plasma aldosterone concentration to plasma renin activity ratio (ARR) on both LIB and RES diets as well as a higher sodium-modulated aldosterone suppression-stimulation index-an indicator of aldosterone dysregulation. In younger Black women-but not in White women-there was a significant association between SBP and ARR on both LIB and RES diets. Young Black women had increased SBP and ARR as compared to White women on LIB and RES diets, which offers insights into the possible mechanisms for the increased hypertension and cardiovascular disease risk in an at-risk and understudied population.

Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma.

Metyrosine (alpha-methyl-para-tyrosine) effectively reduces catecholamine levels in patients with pheochromocytoma/paraganglioma. However, improvements in physiological and metabolic parameters and changes in endocrine function associated with metyrosine administration should be validated in comparison to surgery. This study was performed to confirm the effects of metyrosine on the physiological, metabolic, and endocrinological functions of patients with pheochromocytoma/paraganglioma in the perioperative period. This retrospective cohort study was performed at a single university hospital. We included ten patients with pheochromocytoma/paraganglioma who received oral metyrosine after α-blocker therapy and consecutive surgeries. Urinary catecholamine metabolite levels and other clinical parameters were evaluated before and after metyrosine administration, and 1 week after surgery. The mean age was 53.1 ± 16.1 years. Of the ten participants (four men and six women), nine had pheochromocytoma and one had paraganglioma. The median maximum metyrosine dose was 750 mg/day. Urinary catecholamine metabolite levels significantly decreased in a dose-dependent manner after metyrosine administration. Both systolic and diastolic blood pressure significantly decreased after metyrosine and surgical treatment. Metyrosine administration significantly improved insulin sensitivity, although surgery improved the the basal insulin secretion. Additionally, serum prolactin and thyroid-stimulatory hormone levels were significantly increased by metyrosine treatment, whereas plasma renin activity was decreased. Metyrosine significantly reduced catecholamines in patients with pheochromocytoma/paraganglioma and ensured the safety of the surgery. Adjustment of metyrosine administration may make surgical pretreatment more effective in achieving stabilized blood pressure and improving glucose metabolism. Endocrine parameters may manifest as the systemic effects of metyrosine administration.

META-ANALYSIS OF DEPENDENCE OF THE DEVELOPMENT OF EXPERIMENTAL RENOVASCULAR HYPERTENSION “2 KIDNEYS, 1 CLAMP” ON LIFESTYLE FACTORS

Background. According to WHO controllable hypertension risk factors include an unhealthy diet, physical inactivity, and wrong daily routine. To date, a large number of experimental studies in rats have studied the effect on the development of unilateral renovascular hypertension (URH) of dietary supplements (minerals, vitamins, flavonoids, caffeine, fats, carbohydrates), physical activity and melatonin therapy.Objective. To conduct a meta- analysis of studies on risk factors for the development of URH.Design and methods. The search for publications was carried out in the PubMed, Scopus, Google Scholar databases. A total of 52 publications were selected.Results. The severity of hypertension decreases when the diet is enriched with potassium, as well as with various antioxidants (vitamin C, flavonoids, melatonin), which reduce oxidative stress in the ischemic kidney. In addition, physical activity can help reduce blood pressure in URH, but at the same time, it increases myocardial hypertrophy. There was no hypertensive effect of increased sodium chloride intake in renal artery stenosis, and no effect of calcium or magnesium supplementation on the URH development. At the same time, caffeine intake significantly increases plasma renin activity and blood pressure in URH.Conclusion. The majority of experimental studies included in our meta-analysis investigated the influence of factors on the development of URH, but not their effect on blood pressure in the chronic stage of URH.

Diagnostic Utility of Aldosterone/Direct Renin Concentration Ratio in Iraqi Patients with High Arterial Blood Pressure: A Pilot Study


 
 
 Objectives: Primary aldosteronism is a prevalent contributor to secondary hypertension, posing an elevated risk of morbidity and mortality. The initial step in diagnosing this condition involves screening individuals suspected of having it.
 Methods: In our study, we enrolled 50 patients who were suspected of having hyperaldosteronism. We provided specific recommendations and instructions to these patients concerning drug therapy and implemented measures to enhance testing accuracy. The tests were conducted using the Chemiluminescence Immunoassay (CLIA) system procedure, relying on plasma direct renin concentration rather than activity. Our findings were meticulously validated, compared, and aligned with the references from ARUP laboratories.
 Results: Among our participants, 4 patients (8%) were unequivocally diagnosed with primary aldosteronism based on the Aldosterone Direct Renin Concentration (ADRR) criteria. These patients exhibited the trifecta of hypokalemia, elevated aldosterone levels, and diminished renin levels, obviating the need for further confirmatory testing. Furthermore, 13 patients (26%) were deemed likely candidates for primary aldosteronism, given their plasma aldosterone levels exceeding 15 ng/dl and renin levels below 2.5 pg/ml. Additionally, 7 patients (14%) displayed strong indications of primary aldosteronism, characterized by plasma aldosterone levels surpassing 21 ng/dl and plasma renin concentrations below 2.5 pg/ml, accompanied by high ADRR values. However, both the "likely" and "strong indication" groups necessitated confirmatory testing. Notably, our results revealed no significant disparities in age, gender, personal or family history of atherosclerotic cardiovascular disease (ASCVD), or the presence of adrenal adenomas between patients diagnosed with primary aldosteronism and those in the non-aldosteronism group within the study.
 Conclusion: Primary aldosteronism is a prevalent health concern, warranting the screening of highly suspicious patients. Utilizing direct renin concentration, instead of renin activity, offers a straightforward, cost-effective, rapid, and reproducible method for diagnosis.
 
 

Regulation of the renin-angiotensin-aldosterone system by cyclic nucleotides and phosphodiesterases.

The renin-angiotensin-aldosterone system (RAAS) is one of the key players in the regulation of blood volume and blood pressure. Dysfunction of this system is connected with cardiovascular and renal diseases. Regulation of RAAS is under the control of multiple intracellular mechanisms. Cyclic nucleotides and phosphodiesterases are the major regulators of this system since they control expression and activity of renin and aldosterone. In this review, we summarize known mechanisms by which cyclic nucleotides and phosphodiesterases regulate renin gene expression, secretion of renin granules from juxtaglomerular cells and aldosterone production from zona glomerulosa cells of adrenal gland. We also discuss several open questions which deserve future attention.

Activation of the Renin-Angiotensin-Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy.

Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin-angiotensin-aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.

Genetic Ablation of Prorenin Receptor in the Rostral Ventrolateral Medulla Influences Blood Pressure and Hydromineral Balance in Deoxycorticosterone-Salt Hypertension.

Non-enzymatic activation of renin via its interaction with prorenin receptor (PRR) has been proposed as a key mechanism of local renin-angiotensin system (RAS) activation. The presence of renin and angiotensinogen has been reported in the rostral ventrolateral medulla (RVLM). Overactivation of bulbospinal neurons in the RVLM is linked to hypertension (HTN). Previous studies have shown that the brain RAS plays a role in the pathogenesis of the deoxycorticosterone (DOCA)-salt HTN model. Thus, we hypothesized that PRR in the RVLM is involved in the local activation of the RAS, facilitating the development of DOCA-salt HTN. Selective PRR ablation targeting the RVLM (PRRRVLM-Null mice) resulted in an unexpected sex-dependent and biphasic phenotype in DOCA-salt HTN. That is, PRRRVLM-Null females (but not males) exhibited a significant delay in achieving maximal pressor responses during the initial stage of DOCA-salt HTN. Female PRRRVLM-Null subsequently showed exacerbated DOCA-salt-induced pressor responses during the "maintenance" phase with a maximal peak at 13 d on DOCA-salt. This exacerbated response was associated with an increased sympathetic drive to the resistance arterioles and the kidney, exacerbated fluid and sodium intake and output in response to DOCA-salt, and induced mobilization of fluids from the intracellular to extracellular space concomitant with elevated vasopressin. Ablation of PRR suppressed genes involved in RAS activation and catecholamine synthesis in the RVLM but also induced expression of genes involved in inflammatory responses. This study illustrates complex and sex-dependent roles of PRR in the neural control of BP and hydromineral balance through autonomic and neuroendocrine systems. Graphical abstract.

Circulating renin-angiotensin systems mediated feedback controls over the mean-arterial pressure

The renin-angiotensin systems play pivotal role in cardiovascular physiology through its effects on regulating blood pressure and electrolyte homeostasis. Components of circulating RAS (cRAS) that include precursor angiotensinogen, two critical enzymes (renin and angiotensin-converting enzyme, ACE), their bioactive products, angiotensin- I, II together with its receptors (AT1R and AT2R) essentially determine this homeostasis. Most classical studies, however, showed the deleterious role of cRAS in elevating the blood pressure. Contemporary discovery of non-canonical components of the RAS has challenged this classic hypothesis that it can only exert deleterious effects on the cardiovascular systems. Using the classic cRAS model, we have designed in-silico experiments to test the hypothesis that AT2R-mediated feedback effects play pivotal role for maintaining the normal variation of the mean-arterial pressure (MAP).Beside the AT2R-mediation of downstream singling pathways consisting of several non-canonical RAS components, this study first time illustrated AT2R mediated feedback controls over the blood pressure regulation: one that impedes AT1R activity, and the other that downregulates renin. It has been shown that relatively stronger suppression of renin activity significantly contributes in maintaining the normal MAP and that tight AT2R-mediated regulation is relaxed in hyper-and hypotension. This control mechanism is noted to be robustly maintained with the MAP variations through an established linear steady-state relationship among renin, angiotensin I and angiotensin II. This examination suggests that AT2R-mediated downregulation of renin activities potentially counteracts the AT1R-mediated deleterious actions of Ang II. This study, therefore, provides a solid ground for considering different AT2 receptor adaptor protein and direct agonism at AT2R that can cause greater effects along with contemporary approaches of blocking AT1R mediation to attenuate hypertension or other cardiovascular disorders.

What are the Best Drugs and Combinations in Afro-Descendant Hypertensive Patients?

Hypertension in African descendants occurs early, with high rates of cardiovascular events compared to Caucasians. In addition, genetic influence, low levels of plasma renin activity, greater sensitivity to salt, low sodium secretion, and other mechanisms are involved and discussed in this article. For pharmacological treatment, several studies were evaluated, such as CREOLE, ALLHAT, CARDIA, JHS, REGARDS, AASK, ACCOMPLISH, review articles and meta-analyzes and some guidelines, such as European, American, Brazilian to compare treatment indication. Several pharmacological classes, such as calcium channel blockers, Β-blockers, renin angiotensin system inhibitors, aldosterone and diuretics were included in present review in order to compare utilization and indication for Afro-descendant hypertensive patients. We concluded that several relevant points should be considered in the pharmacological treatment of African descendants that include pathophysiological characteristics, early development of lesions in target organs, in addition to higher rates of cardiovascular and renal events. In addition to lifestyle changes, improved nutrition, combined treatment, probably as a first-line treatment, should be considered as an approach, and the drugs used should aim at blood pressure control and inhibition of the inflammatory process, which results in worse outcomes. It is important to highlight that the representativeness of the Afro-descendant population was unsatisfactory for a robust conclusion. in this population, we can infer from the initial pharmacological treatment the use of thiazide-like diuretics, or dihydropyridine calcium channel blocker should be considered, although the institution of fixed combinations with angiotensin enzyme conversion inhibitors or angiotensin receptor blockers are important in the protection of target organs that occurs earlier and more seriously.

Commutability assessment of candidate reference materials for plasma renin activity measurement: current challenges.

This study aims to evaluate the commutability of external quality assessment (EQA) materials and candidate reference materials (RMs) for plasma renin activity (PRA) assay. Commutabilities of 16 candidate RMs were measured along with 40 clinical samples by the four different routine PRA assays, including three LC‒MS/MS assays and onechemiluminescence immunoassay. Sixteen candidate RMs included native/spiked human plasma pools (small-scale pools with <50 individuals) and current EQA materials (large-scale pools with >1,000 individuals). Difference inbias approach and linear regression with prediction interval approach were adopted to determine the commutability. Two-way variance analysis was used to estimate the effects of spiked and pool size on the commutability. Stability and homogeneity studies were performed. Precision and correlation performance of all assays was acceptable. In the difference in bias approach, thecommutability results were not satisfactory (noncommutability: 14/16) and significant sample-specific effects were detected in assay pairs using different incubation buffers. For the prediction interval approach, no commutability was observed in the spiked small-scale pools; EQA materials (4/9) had more satisfactory commutability among all assays than the small-scale pools (2/7); RMs of large-scale pools tend to have better commutability no matter spiked ornot. Commutable RMs were obtainable but challenging. Current EQA materials with relatively good commutability, stability, and homogeneity were appropriate RMs. Large-scale pools are tending to be commutable. Spiking in small-scale pools was not suggested to prepare RMs. MPs adopting a uniform incubation buffer would be preferable for further commutability research.

Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations

Inappropriate activation of intrarenal renin–angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

Association of Reversal of Renin Suppression With Long-Term Renal Outcome in Medically Treated Primary Aldosteronism.

Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/mL per hour; otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/mL per hour) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/mL per hour). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (-0.46 [95% CI, -0.63 to -0.28] mL/min per 1.73 m2 per year) than those with suppressed posttreatment renin (-1.41 [95% CI, -1.56 to -1.27] mL/min per 1.73 m2 per year; difference, 0.96 [95% CI, 0.72-1.20] mL/min per 1.73 m2 per year). Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

Hyporeninemic hypoaldosteronism in RMND1-related mitochondrial disease

BackgroundRMND1 is a nuclear gene needed for proper function of mitochondria. A pathogenic gene will cause multiple oxidative phosphorylation defects. A renal phenotype consisting of hyponatremia, hyperkalemia, and acidosis is frequently reported, previously considered to be due to aldosterone insensitivity.MethodsClinical features and pathophysiology of three patients will be reported. DNA of these patients was subjected to exome screening.ResultsIn the first family, one pathogenic heterozygous and one highly probable heterozygous mutation were detected. In the second family, a homozygous pathogenic mutation was present. The electrolyte disbalance was not due to aldosterone insensitivity but to low plasma aldosterone concentration, a consequence of low plasma renin activity. This disbalance can be treated. In all three patients, the kidney function declined. In the first family, both children suffered from an unexplained arterial thrombosis with dire consequences.ConclusionsHyporeninemic hypoaldosteronism is the mechanism causing the electrolyte disbalance reported in patients with RMND1 mutations, and can be treated.

Evidence for Impaired Renin Activity in Postural Orthostatic Tachycardia Syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive symptom diversity implies multi-organ involvement that interacts in ways still requiring full exploration. Current understanding of POTS pathophysiology suggests alterations in the renin-angiotensin-aldosterone system as a possible contributing factor. Therefore, we investigated the relationship between the activity of the renin-angiotensin-aldosterone system and hemodynamic parameters in a cohort of POTS patients and controls recruited at a tertiary referral center. The case-control study included 46 patients with POTS (27 ± 9 years), and 48 healthy controls (30 ± 9 years) without orthostatic intolerance. Plasma renin activity, expressed as angiotensin I generation, and plasma aldosterone were measured by enzyme-linked immunosorbent assay and were correlated with hemodynamic parameters obtained during active standing tests. Renin activity was significantly downregulated in POTS patients compared to healthy individuals (median, 3406 ng/mL vs. 9949 ng/mL, p < 0.001), whereas aldosterone concentration did not differ between POTS and healthy controls (median, 218 pmol/L vs. 218 pmol/L, p = 0.26). A significant inverse correlation between renin activity and supine and orthostatic blood pressure levels was observed in healthy individuals (p < 0.05 for all), but not in POTS patients. Renin activity, but not aldosterone concentration, is downregulated in patients with POTS. Moreover, renin activity in POTS is dissociated from supine and standing blood pressure levels in contrast to healthy individuals. These findings suggest impaired renin function in POTS, which may direct future therapeutic approaches.

Improvement of hypertension control and left-ventricular function after cure of primary hyperparathyroidism.

Cardiovascular mortality is significantly higher in patients with primary hyperparathyroidism (PHPT) compared to the general population. The role of the renin-angiotensin-aldosterone system (RAAS) as a mediator of cardiovascular pathology in PHPT is unclear, as is the question whether successful parathyroidectomy (PTX) mitigates hypertension (HT), and left-ventricular (LV) dysfunction. In 45 consecutive, hypercalcemic PHPT patients (91% female, 20 normotensive, mean age 54.6 ± 14.6), laboratory examinations, and 24h ambulatory blood pressure monitoring (ABPM) were performed before, one and six months after successful PTX, while transthoracic echocardiography (TTE) pre- and six months post-PTX. Both in patients with normotension (NT) and HT, lower calcemia and parathyroid hormone (PTH) as well as higher phosphatemia were observed on follow-up, while B-type natriuretic peptide, aldosterone, plasma renin activity, and aldosterone-to-renin ratios were comparable. Six months post-PTX, only in patients with HT, median 24-hour SBP/DBP decreased by 12/6 mmHg, daytime SBP by 10, and nighttime DBP by 5 mmHg. Improvement in BP was observed in approximately 78% of patients with HT. Six months post-PTX, TTE revealed: 1) decrease in median LV mass index (by 2 g/m2) and end-diastolic dimension (by 3mm) among patients with HT; 2) normalization of global longitudinal strain in 22% of patients (comparable between those with NT and HT); 3) a mean 12.7% reduction in left-atrium volume index among patients with HT, which underlay normalization of indeterminate diastolic function in 3 out of 6 patients with HT, who exhibited it at baseline (dysfunction persisted in 2). PTX was shown to significantly reduce BP, LV hypertrophy and diastolic dysfunction parameters in PHPT patients with HT, and improve systolic function in all PHPT patients.

Correlation with renin-angiotensin-aldosterone and glomerular filtration rate in chronic renal failure patients

Background: One of the more significant hormonal systems, the renin-angiotensin-aldosterone system, controls the kidney function, adrenal gland through its effect on the balance of sodium and potassium, blood pressure, fluid volume, and also manages the functions of cardiovascular.&#x0D; Objective: To clarify the interrelationship between renal dysfunction and renin-angiotensin-aldosterone system.&#x0D; Patients and Methods: One hundred samples were collected from December 1, 2022, to February 18, 2023, from Al Shams Medical Laboratories (56 male, and 44) female, age range (of 45-60 years), all of them were volunteers suffering from chronic renal failure in the third stage the average glomerular filtration rate was 35. 70 ± 0.37 125 mL/min/1.73m2. and under conservative treatment. Kidney function test, active renin, angiotensin II, and aldosterone were assessed in the serum of all subjects. The p - value of differences less than 0.05 is measured significant, and uses the statistical package for the social sciences (23) software to calculate the correlation coefficient between various parameters.&#x0D; Results: The result shows relationship between the changes in GFR with creatinine, urea and active renin, the mean GFR showed significant negative correlated with mean creatinine (R = -0.76, p &lt; 0.01. As well as the mean GFR with mean urea (R = -0.64, p &lt; 0.01). The mean GFR also showed significant negative correlated with mean active renin in (R = -0.41, p &lt; 0.01). Also, the mean serum active renin level was significantly positive correlated with mean aldosterone (R =0.33, p &lt; 0.05).&#x0D; Conclusion: Renin enzyme is inversely related to renal dysfunction, so when the glomerular filtration rate decrease, the higher the renin increased, and as a result, the increase in blood pressure in chronic renal failure patients.

Assessing the Activity of Renin and GST in the Serum of Ladies Suffering from Polycystic Ovary Syndrome and COVID-19 to Predict the Danger of Cardiac Disease

The coronavirus-pandemic has a major impact on women's-mental and physical-health. Polycystic-ovary-syndrome (PCOS) has a high-predisposition to many cardiometabolic-risk factors that increase susceptibility to severe complications of COVID-19 and also exhibit an increased likelihood of subfertility. The study includes the extent of the effect of COVID-19-virus on renin-levels, glutathione-s-transferase-activity and other biochemical parameters in PCOS-women. The study included 120 samples of ladies that involved: 80 PCOS-patients, and 40 healthy-ladies. Both main groups were divided into subgroups based on COVID-19 infected or not. Blood-samples were collected from PCOS-patients in Kamal-Al-Samara Hospital, at the period between December until June. Some biochemical parameters were measured for all study-groups, which included: determination of serum renin levels by using the ELISA-technique, GST-activity, lipid-profile. FBS was assessed manually, and hormones were assessed using VIDAS-analyzer-hormones. The result showed a possible relationship between FBS-levels and renin in PCOS-ladies (Stein-Leventhal-Syndrome), while GST-activity were inversely associated with BMI in PCOS-ladies. Also, it was found that the renin-levels were higher in PCOS-patients groups compared with healthy-groups. On the other hand, the renin levels and Glutathione-S-Transferase-activity were lower in PCOS-patients-infected-with-COVID-19 than female-patients-without-COVID-19. The statistical-data-displayed that the level of renin is associated negatively with glutathione-s-transferase-activity in PCOS-cases. Renin level was higher in PCOS-ladies, this may lead to increase renal-dysfunction and risk of cardiovascular-disease that may be expected in patients. A decrease in the antioxidant-capacity may be because the high number of free-radicals that enter the body by the virus and high levels of renin which lead to a higher risk of PCOS-complication like cardiovascular-disease.

Determinants of Renal Micro-Perfusion as Assessed with Contrast-Enhanced Ultrasound in Healthy Males and Females.

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

Associations of Diabetic Retinopathy Severity With High Ambulatory Blood Pressure and Suppressed Serum Renin Levels.

The relationships between serum renin levels, severity of diabetic retinopathy (DR), and 24-hour blood pressure (BP) have not been previously reported. To explore causes for DR and the relationships of 24-hour ambulatory BP, and hormone levels with the severity of DR. The diabetic patients were classified as having no DR, simple DR, or severe DR (preproliferative DR plus proliferative DR) based on funduscopic examination, and we measured 24-hour BP, serum active renin (ARC), aldosterone (SAC), adrenocorticotropic hormone, and cortisol levels in each group. Compared to those with no DR or simple DR, patients with severe DR showed significantly higher 24-hour BPs, including daytime and nighttime systolic and diastolic BP levels, independent of diabetic duration and HbA1c levels. The variability of nighttime systolic BP was greater in patients with severe DR than in those with nonsevere DR, although nocturnal BP reduction was similar between the groups. The ambulatory BPs were significantly inversely associated with ARC. The ARC was significantly lower in severe DR patients than in those with no DR or simple DR (3.2 [1.5-13.6] vs 9.8 [4.6-18.0] pg/mL, P < .05), but there were no differences in SAC in patients taking calcium channel blockers and/or α-blockers. No associations were found between DR severity and other hormone levels. Severe DR was associated with higher 24-hour BPs and suppressed ARC. These findings suggest that mineralocorticoid receptor overactivation may play a role in higher BP levels and severe DR in diabetic patients.