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

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

Abstract The authors investigated the antihypertensive effect of sacubitril/valsartan (Sac/Val) when switching from other drugs and assessed whether brain natriuretic peptide (BNP) or plasma renin activity (PRA) before drug switching was a predictor of blood pressure lowering after switching to Sac/Val. In 92 patients with treated hypertension, clinic blood pressure, plasma BNP, and PRA were examined before and after switching to Sac/Val. Clinic systolic and diastolic blood pressures significantly decreased after drug switching to Sac/Val (p

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

Primary aldosteronism (PA) is the most common form of endocrine hypertension with a frequency between 6 and 20% depending on the severity. It is characterized by renin-independent aldosterone hypersecretion. It is relatively autonomous from the main regulators (angiotensin II, potassium concentration) and is not suppressed by sodium loading. There is a continuum of renin- independent (autonomous) aldosteronism. Even normal aldosterone levels, with suppressed plasma renin activity (PRA), activate the mineralocorticoid receptor (MCR). Therefore, the risk of developing arterial hypertension increases not only among hypertensives, but also in the normotensive population. Aldosterone producingcell clusters (APCCs) in morphologically normal adrenal glands are the histopathological basis for normotensive aldosteronism. Timely treatment of renin-independent aldosteronism makes it possible to prevent cardiovascular complications at an early stage. This extends the use of mineralocorticoid receptor antagonists not only at resistant hypertension. In case of lateralization (unilateral form of PA), surgical treatment is applied (laparoscopic adrenalectomy). [ABSTRACT FROM AUTHOR]

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

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

IntroductionLow-renin hypertension (LRH) accounts for approximately one-third of patients with hypertension and are more prevalent in women and the older adult population. Previous study has found a link between the renin-angiotensin-aldosterone system (RAAS) and sex hormones. However, there are insufficient data on the relationship between LRH and metabolic or musculoskeletal outcomes in older adults.Methods and materialsAmong the 343 participants from a population-based cohort study conducted between May 2018 and August 2019, a total of 256 (86 men older than 50 years and 170 postmenopausal women) were included. The presence of LRH was defined as plasma renin activity (PRA)

Background: Previous studies have reported the direct or indirect relationship between the renin-angiotensin-aldosterone system (RAAS) and atrial fibrillation (AF). However, in patients with “apparently” idiopathic AF without possible external influence, whether RAAS is dysregulated at an early stage of AF and its relationship with the recurrence of AF after ablation have not been studied. Methods: This single-center, prospective, case-control study included apparently healthy individuals with AF (the case group) or paroxysmal supraventricular tachycardia (PSVT, the control group) referred for catheter ablation at the same period. The primary outcome was RAAS activation in these two groups. The secondary outcome was the 1-year recurrence of AF after ablation. Results: This study included 51 “apparently” idiopathic AF and 91 patients with PSVT. A greater proportion of patients in the case group had plasma renin activity (PRA) levels

Is any specific organ protection by blocking the renin-angiotensin system? What is the role of the renin-angiotensin system (RAS) in progressive renal disease? The renoprotective effect of ACE-inhibitors and angiotensin II (Ang II) receptor blockers is not only mediated via their renal hemodynamic effects, but also through non-hemodynamic mechanisms? What is the clinical evidence for the importance of local renin-angiotensin system (RAS)? These are several questions of a medical reality: that pharmacological blockade of reninangiotensin system (RAS) is paradoxically effective although circulating plasma renin activity (PRA) is low. An overview of the normal function of the system, as well as ramifications of its dysfunction (overactivity) and potentials for therapeutic blockade, is provided below. [ABSTRACT FROM AUTHOR]

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

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

(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. [ABSTRACT FROM AUTHOR]

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

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

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

Abstract Background Reninoma is a rare, benign renal neoplasm. Typical clinical features include severe hypertension, secondary hyperaldosteronism, hypokalaemia and metabolic alkalosis caused by the overproduction of renin. Case presentation A 25-year-old lean Chinese woman with no family history of hypertension was hospitalized for stage 1 hypertension that gradually developed over two years. Endocrine investigation showed hyperreninemia without hyperaldosteronism and hypokalaemia. Interestingly, although the patient had an elevated plasma renin concentration (PRC), her plasma renin activity (PRA) was in the normal range. Abdominal contrast-enhanced computed tomography (CT) scanning revealed a solid, low-density, renal cortical mass with delayed enhancement. Selective renal vein sampling (SRVS) was performed, and a lateralization of the renin secretion from the left kidney was found. Enucleation of the tumour led to a rapid remission of hypertension and hyperreninemia. Based on pathological findings, the patient was diagnosed with reninoma. Immunohistochemical staining of the tumour was positive for Renin, CD34, Vimentin, and synaptophysin (Syn) and negative for somatostatin receptor 2 (SSTR2) and chromogranin A (CgA). Conclusions Reninoma can present as mild hypertension without hyperaldosteronism and hypokalaemia. The clinical features of reninoma may depend on the degree of activation of the renin-angiotensin-aldosterone system (RAAS). PRC should be incorporated in the differential diagnosis of secondary hypertension.

Abstract Background Information regarding changes in renin‐angiotensin‐aldosterone system (RAAS) during cardiac remodeling after mitral valvuloplasty (MVP) in dogs remains lacking. Hypothesis/Objectives To assess the longitudinal effects of MVP on circulating RAAS activity. Animals Eight client‐owned dogs receiving MVP for myxomatous mitral valve disease (MMVD). Methods This is a cohort study. Plasma renin activity (PRA), angiotensin II (AT2), aldosterone (PAC), blood urea nitrogen (BUN), and creatinine concentrations, were measured in these dogs before (baseline) and at 3 consecutive monthly follow‐ups (Post‐1M, Post‐2M, Post‐3M). Echocardiography was concomitantly used to assess the process of cardiac recovery after MVP. Results The echocardiography revealed a significant decrease in LVIDDN, LA/Ao, FS, E velocity, E/A, E′ sep, S′ lat, E′ lat, and A′ lat after MVP compared with baseline (P

Background: Renal dynamic scans (RDS) despite being considered the gold standard for the diagnosis of pelvic ureteric junction obstruction (PUJO), fail to help resolve the dilemma about management issues in many patients. Multiple invasive and noninvasive methods are being studied to help the decision-making in these patients. We did this study to find correlation of plasma renin activity (PRA) values and resistive index (RI) on Doppler ultrasound with findings of RDS in patients with the Society for Fetal Urology (SFU) Grades 3 and 4 unilateral hydronephrosis (HDN) and also to determine the cut-off values of PRA and RI that could categorically acknowledge the success of pyeloplasty. Methodology: Twenty patients with SFU Grades 3 and 4 unilateral HDN due to PUJO were enrolled. Demographic details were recorded. All underwent Anderson-Hynes dismembered pyeloplasty. Based on the follow-up RDS scans, these patients could fall into one of three categories- improved (successful), status quo, or deteriorated (unsuccessful). Outcomes were compared based on RDS (split renal function [SRF]), ultrasonography, and Doppler findings were done at 3 months of postoperative period. Results: Follow up period was 3 months after Pyeloplasty. Seventeen patients had successful outcomes based on RDS findings, 12 had improvement in SRF (>5%), and 6 had normal drainage curves (t-t1/2

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

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Science for Health issued approval reference number 2022-10-06-01, dated October 22, 2022. Written informed consent was deemed as not necessary as the study involved retrospective data analysis – medical record review only. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Garg et al.)

Objective: Mineralocorticoid receptor antagonists are the recommended medical therapy for bilateral primary aldosteronism (BPA). Patients with BPA have higher risk of cardiocerebrovascular disease (CCVD) than those with essential hypertension. There is no consensus on the criteria to assess the effectiveness of medical therapy for BPA. This study aimed to investigate the incidence of and risk factors for CCVD after medical therapy of BPA., Methods: We conducted a retrospective cohort study including 240 patients with BPA treated with mineralocorticoid receptor antagonists. The posttreatment plasma renin activity (PRA) was defined as unsuppressed (PRA, ≥1 ng/mL/h); otherwise, it was defined as suppressed. We analyzed the association of posttreatment PRA status with CCVD outcomes., Results: Of patients with BPA, 7.1% (17/240) developed CCVD at a median follow-up of 5.0 (range, 2.96-7.66) years. Moreover, 57.1% of patients had a PRA of ≥1 ng/mL/h after treatment. Patients with a PRA of <1 ng/mL/h had a higher incidence of CCVD (12.6% vs 2.9%, P < .05) and were at higher risk than those with a PRA of ≥1 ng/mL/h (hazard ratio, 4.50 [95% CI, 1.47-13.83; P < .05]; adjusted hazard ratio, 3.98 [95% CI, 1.22-13.02; P < .05])., Conclusion: Patients with BPA who receive pharmacologic treatment have a high incidence of CCVD. PRA may be an indicator that mineralocorticoids are being adequately antagonized., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Abstract Background The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. Methods Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. Results Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. Conclusions In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

Background: Reninoma is a rare, benign renal neoplasm. Typical clinical features include severe hypertension, secondary hyperaldosteronism, hypokalaemia and metabolic alkalosis caused by the overproduction of renin. Case presentation: A 25-year-old lean Chinese woman with no family history of hypertension was hospitalized for stage 1 hypertension that gradually developed over two years. Endocrine investigation showed hyperreninemia without hyperaldosteronism and hypokalaemia. Interestingly, although the patient had an elevated plasma renin concentration (PRC), her plasma renin activity (PRA) was in the normal range. Abdominal contrast-enhanced computed tomography (CT) scanning revealed a solid, low-density, renal cortical mass with delayed enhancement. Selective renal vein sampling (SRVS) was performed, and a lateralization of the renin secretion from the left kidney was found. Enucleation of the tumour led to a rapid remission of hypertension and hyperreninemia. Based on pathological findings, the patient was diagnosed with reninoma. Immunohistochemical staining of the tumour was positive for Renin, CD34, Vimentin, and synaptophysin (Syn) and negative for somatostatin receptor 2 (SSTR2) and chromogranin A (CgA). Conclusions: Reninoma can present as mild hypertension without hyperaldosteronism and hypokalaemia. The clinical features of reninoma may depend on the degree of activation of the renin-angiotensin-aldosterone system (RAAS). PRC should be incorporated in the differential diagnosis of secondary hypertension. [ABSTRACT FROM AUTHOR]

Background: Information regarding changes in renin‐angiotensin‐aldosterone system (RAAS) during cardiac remodeling after mitral valvuloplasty (MVP) in dogs remains lacking. Hypothesis/Objectives: To assess the longitudinal effects of MVP on circulating RAAS activity. Animals: Eight client‐owned dogs receiving MVP for myxomatous mitral valve disease (MMVD). Methods: This is a cohort study. Plasma renin activity (PRA), angiotensin II (AT2), aldosterone (PAC), blood urea nitrogen (BUN), and creatinine concentrations, were measured in these dogs before (baseline) and at 3 consecutive monthly follow‐ups (Post‐1M, Post‐2M, Post‐3M). Echocardiography was concomitantly used to assess the process of cardiac recovery after MVP. Results: The echocardiography revealed a significant decrease in LVIDDN, LA/Ao, FS, E velocity, E/A, E′ sep, S′ lat, E′ lat, and A′ lat after MVP compared with baseline (P <.05). There was a significant reduction in the PRA (2.45, 3.05, 2.74 vs 8.8 ng/mL/h; P =.002), AT2 (466, 315, 235 vs 1200 pg/mL; P =.009), and PAC (39.88, 47, 54.62 vs 179.5 pg/mL; P =.01), respectively at Post‐1M, Post‐2M, Post‐3M compared to the baseline. Additionally, BUN and creatinine concentrations decreased from Post‐1M. The RAAS variables showed significant, weak to moderate, relationship with selected echocardiographic variables. Conclusions and Clinical Importance: Mitral valvuloplasty contributes to decreased RAAS activity in MMVD dogs, which paralleled the process of cardiac reverse remodeling up to Post‐3M. This information facilitates formulating strategies to optimize clinical outcomes for dogs after MVP. [ABSTRACT FROM AUTHOR]

Background: To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA). Methods: The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols. Results: When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management. Conclusion: With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients.

Purpose Excessive aldosterone secretion causes a high risk of cardio-cerebrovascular events. Mineralocorticoid receptor antagonist (MRA) is 1 of the treatment strategies for primary aldosteronism (PA). However, current MRA treatment is insufficient because MRA-treated patients with suppressed plasma renin activity (PRA) < 1 ng/mL/h still had a higher risk of cardiovascular disease than those with unsuppressed PRA. This is a prospective interventional study to determine the effects of an increase in MRA dosage on blood pressure (BP) control and urinary albumin excretion (UAE) in MRA-treated PA patients. Methods Thirty-four PA patients were recruited, and 24 patients (6 male, 18 female) completed this study. Serum potassium concentration was assessed every two months to adjust the dosage of MRA safely for 6 months. The primary outcomes were the changes in BP and UAE between baseline and 6 months. Results Systolic BP (SBP) and log10UAE decreased significantly as the daily dose of MRA increased. Diastolic BP (DBP) tended to decrease. We divided the PA patients into two groups (baseline PRA < 1 ng/mL/h and baseline PRA ≥ 1 ng/mL/h) according to PRA. In the group with baseline PRA < 1 ng/mL/h but not that with baseline PRA ≥ 1 ng/mL/h, SBP, DBP and log10UAE after 6 months were significantly lower than those at baseline. Conclusions The increase in MRA dosage improved BP and UAE in PA patients with suppressed PRA. [ABSTRACT FROM AUTHOR]

Abstract Background To study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia. Methods A single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction. Results Renin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07–55.58)] and AGT [OR = 3.53; 95% CI (1.02–12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03–27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21–22.30), р = 0.029]. Conclusion An in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control.

Abstract Background Large-volume paracentesis (LVP) is a main pillar in treating patients with tense ascites. Without plasma expanders use, paracentesis-induced circulatory dysfunction (PICD) is a common complication with decreased survival. The aim was to compare low-dose albumin (2 g/L ascitic fluid removed n = 85) with standard-dose albumin (6 g/L ascitic fluid removed, n = 25) for prevention of PICD. Liver function tests, urea, creatinine, CBC, and abdominal ultrasonography were done. Plasma renin activity (PRA) was measured at baseline and on the 6th day post-LVP. The delta change (Δ) = day 6 variable minus baseline variable value. PICD was defined as increase in PRA of > 50% of the baseline value. Results Patients in low-dose albumin group were mainly Child B compared with Child C (85.9% vs. 52%; p = 0.001), underwent less paracentesis volume (9.78 ± 3.56 vs. 12.52 ± 3.6 L; p = 0.001), but had higher baseline PRA (859.62 ± 1151.34 vs. 165.93 ± 95.34 pg/mL; p = 0.001). In both groups, the PRA increased at day 6 compared with the baseline (1141.57 ± 1433.01 vs. 859.62 ± 1151.34 pg/mL; p = 0.01) and (192.21 ± 80.99 vs. 165.93 ± 95.34 pg/mL; p = 0.01) respectively. Both groups were comparable for Δ PRA (281.95 ± 851.4 vs. 26.28 ± 30.2 pg/mL; p = 0.102) and PRA percent increase (10.97 ± 30.77 vs. 12.57 ± 14.87; p = 0.844). They had comparable PICD incidence (24.7% vs. 12%; p = 0.27). Females were more liable for PICD occurrence than males (OR 2.91, 95% CI 1.125–7.547, p = 0.028) and so Child B patients than Child C (OR 8.4, 95% CI 1.072–65.767, p = 0.043). Conclusion Low-dose albumin infusion is comparable to the standard-dose albumin for the prevention of PICD.

Background: The blood pressure (BP)-lowering effect of sacubitril/valsartan (Sac/Val) is greater than that of angiotensin II receptor blockers (ARBs) but in in real-world clinical practice, Sac/Val is used in a variety of patterns other than switching from ARBs. In the present study we investigated the effects of Sac/Val on BP and biochemical parameters when switching from or adding it to various antihypertensive drugs and examined what factors could be predictors of the antihypertensive effect of Sac/Val. Methods and Results: In 108 hypertensive patients treated with antihypertensive agents (including 4 naïve cases), clinic BP and various biochemical parameters were assessed before and after switching to/adding Sac/Val (200 mg/day). Systolic and diastolic BPs significantly decreased after treatment with Sac/Val (P<0.0001, respectively). As for biochemical parameters, alanine aminotransferase, triglycerides, C-reactive protein, and uric acid significantly decreased after administration of Sac/Val, but renal function, B-type natriuretic peptide, and plasma renin activity (PRA) did not change before or after treatment with Sac/Val. Multiple regression analysis revealed that low PRA and high baseline systolic BP were independent determinants of systolic BP reduction after Sac/Val treatment. Conclusions: Sac/Val is beneficial for poorly controlled hypertension in daily clinical practice and low PRA may be a predictor of the antihypertensive effect of switching to/adding Sac/Val., Competing Interests: T. Horio received personal fees for lectures from Novartis Pharma and Otsuka Pharmaceutical. D.F. received personal fees for lectures from Novartis Pharma and Otsuka Pharmaceutical, and received a scholarship grant from Otsuka Pharmaceutical. M.Y. is a member of Circulation Reports’ Editorial Team. The other authors have no conflicts of interest to disclose., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Background: The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.Objectives: The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.Methods: Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.Results: Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.Conclusions: Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749). [ABSTRACT FROM AUTHOR]

Aims: Plasma renin activity (PRA) is regarded as a marker of sodium and fluid homeostasis in patients with primary hypertension. Whether effects of diuretics on PRA differ according to class of diuretic, whether diuretics lead to a sustained increase in PRA, and whether changes in PRA relate to those in blood pressure (BP) is unknown. We performed a systematic review and meta‐analysis of trials investigating the antihypertensive effects of diuretic therapy in which PRA and/or other biomarkers of fluid homeostasis were measured before and after treatment. Methods: Three databases were searched: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials. Titles were firstly screened by title and abstract for relevancy before full‐text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria. Results: A total of 1684 articles were retrieved of which 61 met the prespecified inclusion/exclusion criteria. PRA was measured in 30/61 studies. Diuretics led to a sustained increase in PRA which was similar for different classes of diuretic (standardised mean difference [95% confidence interval] 0.481 [0.362, 0.601], 0.729 [0.181, 1.28], 0.541 [0.253, 0.830] and 0.548 [0.159, 0.937] for thiazide, loop, mineralocorticoid receptor antagonists/potassium‐sparing and combination diuretics respectively, Q = 0.897, P =.826), and did not relate to the average decrease in blood pressure. Conclusion: In antihypertensive drug trials, diuretics lead to a sustained increase in average PRA, which is similar across different classes of diuretic and unrelated to the average reduction in blood pressure. [ABSTRACT FROM AUTHOR]

Background: The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. Methods: Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. Results: Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. Conclusions: In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Plasma renin activity (PRA) has been related to all-cause mortality and cardiovascular events in patients with cardiovascular disease. However, data from patients with acute coronary syndromes (ACS) are sparse. Determination of PRA was made in 550 patients with ACS, including a subgroup of 287 patients not on treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or diuretics, and without heart failure. We evaluated the relations between PRA and all-cause mortality after three years and long-term, and to cardiovascular events after median 8.7 years. Adjustments were made for variables that influenced the hazard ratio (HR) > 5% for the relation between PRA and outcome. Baseline PRA was associated with all-cause mortality during three-years (unadjusted HR 1.74 per 1 SD increase in logarithmically transformed PRA; 95% confidence interval (CI) 1.39–2.16, p < 0.0001) and long-term (HR 1.12, CI 1.00–1.25, p = 0.046). After adjustments, only the three-year association remained significant. In unadjusted analyses, PRA was associated with cardiovascular death, but not with nonfatal cardiovascular events. In the subgroup there was an inverse relation between PRA and long-term all-cause mortality. Higher PRA was a significant independent predictor of all-cause mortality after three years, but not at long-term follow-up and not significantly associated with cardiovascular incidence. The renin-angiotensin-system pathophysiology is of great interest, not least due to its association with the COVID-19 pandemic. Our findings indicate a need for further research on the prognostic/predictive aspects of the renin-angiotensin-system in ACS. • PRA is associated with three-year mortality in patients with ACS. • This association appears to be inverse in ACS patients without need for RAS-blocking drugs or diuretics. • PRA levels is associated with markers of inflammation and myocardial injury. • With better understanding of the role of RAS in CV disease more effective end-organ protection will be possible. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the relations between plasma renin activity (PRA), serum aldosterone concentration (ALDO) and selected asymptomatic organ damage (AOD) indices in mild primary arterial hypertension (AH).Material and Methods: We measured PRA, ALDO, and selected AOD indices (carotid-femoral pulse wave velocity (cfPWV), central aortic pulse pressure (cPP), estimated glomerular filtration rate (eGFR)) in 122 patients with untreated AH.Results: Patients with high PRA (≥ 0.65 ng/ml/h) were characterized by lower plasma sodium and aldosterone to renin ratio (ARR), higher ALDO, but a similar level of AOD indices compared to patients with low PRA. cfPWV (p = 0.04) and cPP (p = 0.019) increased with ARR, while eGFR decreased with ALDO (p = 0.008). Only eGFR was independently correlated with ALDO. In subjects with simultaneously high PRA and ARR values, we found significantly higher cfPWV (p = 0.02) and cPP (p = 0.04) and lower eGFR (p = 0.02) than in those with high PRA but low ARR values.Conclusions: Assessment of the influence of the renin-angiotensin-aldosterone system (RAAS) on AOD should include the relationship between renin and aldosterone. The PRA itself has no predictive value for AOD. More advanced arterial stiffness and renal impairment are associated with increased PRA and ARR. The RAAS activity might be useful in AOD prediction and hypertension severity assessment. [ABSTRACT FROM AUTHOR]

Background: To update information about the internationally accepted standards and clinical recommendations for the detection and diagnosis of primary aldosteronism (PA).Methods: The Taiwan Society of Aldosteronism (TSA) Task Force reviewed the latest literature and reached a consensus after group meetings. The nine critical issues were recognized to provide updated information and internationally acceptable protocols.Results: When screening for PA by using the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR), withdrawal or adjustment of antihypertensive medication is not always necessary on the first patient visit. Hypokalemia should be corrected before ARR screening. In spontaneous hypokalemia, plasma renin below detection levels, and PAC higher than 20 ng/dL (550 pmol/L), further confirmatory testing is unnecessary for PA diagnosis. Direct renin concentration (DRC) could be used for PA diagnosis if PRA is unavailable. Although additional confirmatory tests are suggested, the result of a single test is still reliable. For patient safety, discontinuation or adjustment of antihypertensive medications is indicated before adrenal venous sampling (AVS). ACTH could be beneficial for successful adrenal vein cannulation but is not necessary for determining lateralization in AVS. Simultaneous technique is preferred for AVS. Adrenal NP-59 scintigraphy integrated with SPECT/CT could guide PA management.Conclusion: With introduction of these new concepts to the clinicians, we expect better identification, management and treatment of PA patients. [ABSTRACT FROM AUTHOR]

BackgroundAlthough higher plasma renin activity (PRA) is associated with poor clinical outcomes including higher death and cardiovascular events, its association with prevalence of chronic kidney disease (CKD) is not clear. We hypothesized that higher levels of PRA and lower levels of aldosterone-to-PRA ratios (ARRs) are associated with greater CKD prevalence in a large and ethnically diverse population of southern California who underwent uniform healthcare.MethodsDuring the period 1 January 1998 to 31 October 2009, the adult population who was under the care of Kaiser Permanente Southern California with documented outpatient values of PRA and minimum of 6 months continuous enrollment were examined. CKD defined by an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2. PRA levels and ARR were categorized into quartiles. Multivariate logistic regressions were used to calculate odds ratios for CKD based on PRA controlling for age, sex, black race, diabetes status, hypertension, and type of medication use.ResultsWe identified 9495 individuals including 7887 with hypertension. Study population included 60% women, 35% whites, 20% blacks, 20% Hispanics, and 26% diabetic patients. Adjusted odds ratios (95% confidence interval) for CKD across second, third, and fourth quartiles of PRA quartile (reference: first quartile) were 1.5 (1.2-1.7), 1.5 (1.3-1.8), and 2.2 (1.9-2.6), respectively. Each 10-unit increase in PRA was associated with odds ratio for CKD of 1.3 (1.2-1.4). ARR showed a similar but inverse trend with CKD.ConclusionHigher levels of PRA are associated with greater rates of CKD in our large ethnically diverse population of primarily hypertensive patients. Whether modulation of PRA can mitigate prevalence of CKD needs to be studied in interventional trials.

The purpose of this systematic review was to investigate the scientific evidence to support the use of direct renin inhibitors (DRIs) in diabetic nephropathy (DN). MEDLINE was searched for articles reported until 2018. A standardized dataset was extracted from articles describing the effects of DRIs on plasma renin activity (PRA) in DN. A total of three clinical articles studying PRA as an outcome measure for DRIs use in DN were identified. These clinical studies were randomized controlled trials (RCTs): one double-blind crossover, one post hoc of a double-blind and placebo-controlled study, and one open-label and parallel-controlled study. Two studies reported a significant decrease of albuminuria associated with PRA reduction. One study had a DRI as monotherapy compared with placebo, and two studies had DRI as add-in to an angiotensin II (Ang II) receptor blocker (ARB). Of 10,393 patients with DN enrolled in five studies with DRI, 370 (3.6%) patients had PRA measured. Only one preclinical study was identified that determined PRA when investigating the effects of aliskiren in DN. Moreover, most of observational preclinical and clinical studies identified report on a low PRA or hyporeninemic hypoaldosteronism in DM. Renin inhibition has been suggested for DN, but proof-of-concept studies for this are scant. A small number of clinical and preclinical studies assessed the PRA effects of DRIs in DN. For a more successful translational research for DRIs, specific patient population responsive to the treatment should be identified, and PRA may remain a biomarker of choice for patient stratification.

The clinical characteristics and surgical prognosis of glucocorticoid-remediable aldosteronism (GRA, also known as familial hyperaldosteronism type 1, FH-I) have not been widely studied. Using data from the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry retrospectively, we describe the associated clinical factors for GRA and clinical predictors of surgical outcomes among identified GRA patients. We found 79 GRA-positive (51.2 ± 13.8 years; women 39 (49.4%)) and 114 GRA-negative primary aldosteronism (PA) patients matched with age, gender, and body mass index. Lower plasma aldosterone concentrations (PACs) and aldosterone-renin ratios were found among GRA-positive individuals. Multivariable logistic regression demonstrated that a PAC ≤ 40 ng/dL could predict concealed GRA individuals (OR 0.523, p = 0.037). Low serum potassium (OR 0.285, p = 0.008), but not the presence of GRA, was associated with hypertension-remission. Of note, PRA (OR 11.645, p = 0.045) and hypokalemia (OR 0.133, p = 0.048) were associated with hypertension-remission in GRA patients. Unilateral primary aldosteronism patients harboring concomitant GRA were not associated with inferior hypertension-remission after an adrenalectomy. Low serum potassium and high PRA were positively associated with hypertension-remission in GRA patients.

The Phase Plane method enables the dynamic processes to be explored without the need to solve the differential equations describing them. This is due to the fact that the phase plane provides ways to present the experimental data that underlines the dynamic behavior of the system. The plasma renin activity following a treatment with nifedipine is analyzed in the present study. The phase trajectories are built for different drug doses, while the equilibrium points and their type are determined. Graphs of the state-space variables are constructed and their parameters -- the extreme values and the area under the curve - are calculated. The results show that extreme values are obtained at doses of nifedipine ranging from 40.5 mg/kg b.w. to 42.25 mg/kg b.w. The results reported are obtained by the KORELIA program. This approach contributes to the enrichment of the tools used by the biology scientists by enabling them to use a complex mathematical theory for the characterization of the dynamic behavior of the studied systems by using a program with a friendly graphical interface. [ABSTRACT FROM AUTHOR]

Background: Despite advances in non‐invasive vascular imaging, detection of renal artery stenosis via catheter angiography is the criterion standard for the diagnosis of renovascular hypertension (RVH). However, because of lack of evidence, the utility of various blood tests and imaging modalities remains unclear. Methods: We retrospectively analyzed the utility of blood tests (plasma renin activity [PRA], aldosterone, and renal vein renin [RVR] values) and imaging studies (computed tomography angiography [CTA], kidney ultrasonography [US]) by comparing them with catheter angiography. Ten pediatric patients with RVH at two institutions from January 2008 to December 2017 were recruited. The sensitivities for diagnosing RVH via imaging and blood tests (kidney [US], PRA, and aldosterone) were derived by examining patient records. Furthermore, the sensitivity and specificity of CT angiography were calculated by considering both the affected and non‐affected renal arteries of the patients. Results: A high sensitivity for diagnosing RVH via kidney US (89%) and PRA (80%) was observed. The sensitivity and specificity of CTA were 100%, each. RVR sampling did not aid in the diagnosis of RVH; only two of six patients with unilateral RVH showed significant laterality of RVR boundary ratios. Renal scintigraphy facilitated detection of a non‐functional kidney (split renal function <5%). Conclusions: RVH in children could be diagnosed utilizing non‐invasive blood and imaging tests, without catheter angiography. We recommend kidney length measurement along with measurement of PRA level, as a simple and highly useful screening test, followed by CTA as a diagnostic test. [ABSTRACT FROM AUTHOR]

Background: To study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia.Methods: A single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction.Results: Renin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07-55.58)] and AGT [OR = 3.53; 95% CI (1.02-12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03-27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21-22.30), р = 0.029].Conclusion: An in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control. [ABSTRACT FROM AUTHOR]

Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30.Methods and Results: A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20-75 mL/min/1.73 m2 . The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P < 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01-1.23, P = 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02-1.26, P = 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02-1.37, P = 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01-1.32, P = 0.04).Conclusion: Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF. [ABSTRACT FROM AUTHOR]

Plasma renin activity (PRA) is a predictive biomarker of blood pressure (BP) response to antihypertensives in European–American hypertensive patients. We aimed to identify the metabolic signatures of baseline PRA and the linkages with BP response to β-blockers and thiazides. Using data from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) trial, multivariable linear regression adjusting for age, sex and baseline systolic-BP (SBP) was performed on European–American individuals treated with metoprolol (n = 198) and chlorthalidone (n = 181), to test associations between 856 metabolites and baseline PRA. Metabolites with a false discovery rate (FDR) < 0.05 or p < 0.01 were tested for replication in 463 European–American individuals treated with atenolol or hydrochlorothiazide. Replicated metabolites were then tested for validation based on the directionality of association with BP response. Sixty-three metabolites were associated with baseline PRA, of which nine, including six lipids, were replicated. Of those replicated, two metabolites associated with higher baseline PRA were validated: caprate was associated with greater metoprolol SBP response (β = −1.7 ± 0.6, p = 0.006) and sphingosine-1-phosphate was associated with reduced hydrochlorothiazide SBP response (β = 7.6 ± 2.8, p = 0.007). These metabolites are clustered with metabolites involved in sphingolipid, phospholipid, and purine metabolic pathways. The identified metabolic signatures provide insights into the mechanisms underlying BP response.