Plasma Renin Concentration Research Articles

The effect of 30 min of supine rest on plasma renin concentrations in paediatric patients.

The aim of this study is to interpret plasma renin concentrations (PRCs) correctly in a clinical setting, it is essential to understand to what extent physical activity influences the concentration. Reference values for different postural positions exist for adults, but data for children are sparse. In this study, the effect of 30 min of rest on plasma renin concentrations in paediatric patients was examined. In total, 41 paediatric patients, undergoing either arginine or clonidine provocation tests for growth hormone deficiency, were included. For each stimulation test, two blood samples were drawn. One at time 0 min and one after 30 min of rest. In total, renin concentrations were determined in 86 serum samples. Renin concentrations decreased from 0 to 30 min with a median value of -20.5% (inter-quartile range: -33.0% to -12.8%). This decrease was not dependent on sex, age, medication or comorbidity, and the variance of renin did not differ between 0 and 30 min. Renin concentrations in children differ according to postural position, which is comparable to adults. Thus, the clinical interpretation of renin results needs to consider the preanalytical conditions applied in the local reference population.

Relationship between renin, aldosterone, aldosterone-to-renin ratio and left ventricular mass index in young adults

Abstract Background Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, especially in middle-aged and elderly populations. It is unclear if early changes in PA biomarkers can affect left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases. Aim To evaluate the relationship between PA biomarkers, namely renin concentration, aldosterone concentration and aldosterone-to-renin ratio (ARR), and LVMI in young adults. Methods The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27. Participants with PA biomarkers and LVMI measured by cardiac magnetic resonance imaging were included. Females who were on oral contraception were excluded due to its confounding effect on the ARR. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results Of 758 participants, 252 (33.2%) were females and the mean (SD) age was 26.7 (0.4) years. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m²; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusion An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function. One may speculate that an intervention trial in young adults with subclinical PA is warranted to determine the role of aldosterone blockade in preventing future cardiovascular diseases.

7787 Primary Aldosteronism Medical Treatment Outcomes (PAMO): An International Consensus on Outcome Assessment Criteria and Multicentre Study

Abstract Disclosure: J. Yang: None. J. Burrello: None. J. Goi: None. T.A. Williams: None. W.F. Young: Consulting Fee; Self; Arena Pharmaceuticals, Inc.. Other; Self; Crinetics Pharmaceuticals. P.J. Fuller: None. P. Investigators: None. Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Mineralocorticoid receptor antagonists, at adequate doses, lower blood pressure and cardiovascular risk in patients with PA. However, there is a lack of a standardized approach to medical therapy and subsequent outcomes assessment. We aimed to: 1) establish criteria for assessing outcomes of targeted medical treatment of PA, and 2) evaluate outcomes using these criteria across an international cohort. A panel of 31 PA experts from 31 centres across four continents used the Delphi method, including three rounds of online questionnaires, to reach consensus. Clinical data were then collected from consecutive patients with PA who started targeted medical treatment between 2016 and 2021 at the participating centres. Consensus was reached for six outcomes, including complete, partial, or absent biochemical response, and complete, partial, or absent clinical response. “Complete biochemical response” was defined as “correction of hypokalemia without potassium supplementation, and normalization of plasma renin activity or concentration”; while “absent biochemical response” was defined as “persistent hypokalemia and/or persistently suppressed or low plasma renin activity or concentration without change from baseline”. “Complete clinical response” was defined as “normal blood pressure without additional antihypertensive medications”; while “absent clinical response” was defined as “the same or increased blood pressure compared to before targeted treatment with same or more antihypertensive medications, not counting targeted therapy”. Of 1483 patients (mean age 52y, 48% female) from 28 centers, 232 (16%) had a complete clinical response, and 719 (49%) had a complete biochemical response at the most recent follow-up (median 29 months after treatment initiation). Compared to those with partial or absent clinical response, patients with complete clinical response had a significantly higher proportion of women and lower proportion with diabetes, stroke or left ventricular hypertrophy. They also had a significantly shorter duration of hypertension, lower BMI, higher eGFR and lower defined daily dose of antihypertensives at baseline. In contrast, these differences were not observed in those with a complete, partial or absent biochemical response. The defined daily dose of targeted therapy did not differ across the various response categories. In conclusion, we have established an international expert consensus for standardized criteria to evaluate the response to targeted medical treatment of PA, facilitate comparisons of outcome data and guide clinicians who manage PA. In a retrospective international cohort, less than half of medically-treated patients reached the established biochemical treatment targets. Further work is needed to increase the rate of complete response. Presentation: 6/3/2024

12215 A Rare Cause Of Cushing's Syndrome: Acth-producing Pheochromocytoma

Abstract Disclosure: S. Jimenez Salazar: None. C. Aguilar Londoño: None. N. Aristizabal Henao: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Cushing's syndrome is a severe endocrine disorder caused by chronic, autonomous, and excessive cortisol secretion. Among all causes, ectopic ACTH production continues to be one of the most challenging diagnoses. Rarely, pheochromocytomas secrete hormones other than catecholamines, including ACTH and CRH. The secretion of these hormones can alter the clinical presentation and make the diagnosis more difficult. Clinical Case: A previously 60-year-old woman with hypertension and no other relevant medical history presented with unintentional weight loss of 16 kg and constipation. Physical examination revealed a moon face, supra-labial and chin facial hair. Laboratory studies demonstrated hypokalemia (potassium 3.02 mEq/L, n: 3.5-5 mEq/L) and newly diagnosed diabetes (HbA1c 8.69%, n <5.7% and fasting glucose 282 mg/dL, n: 70-100 mg/dL), both difficult to control. Considering the clinical and biochemical findings, hypercortisolism was evaluated by measuring 24-hour urinary free cortisol (1853 mcg/24h, n: 4-176 mcg/24h), nocturnal serum cortisol (40.9 mcg/h, n:<7.5 mcg/h), and 1 mg dexamethasone suppression test (43.1 mcg/h, n:<1.8 mcg/h), confirming cortisol excess. ACTH was measured (95 pmol/mL, n: 4.7-48.5 pg/mL) suggesting ACTH-dependent cause, leading to a dynamic test with high doses of dexamethasone (8mg) with suppression greater than 50% and normal pituitary MRI, both compatible with an extrahypophyseal cause. Peripheral imaging evaluation was conducted with cervical-thoracic CT scan and abdominal MRI confirming the presence of a complex adrenal mass. Among adrenal hyperfunction studies, primary hyperaldosteronism was ruled out (Aldosterone 9.8 ng/dL, n: 1-32 ng/dL and Plasma Renin Concentration 1.1 ng/dL, n: 0.16-2.3 ng/dL), and pheochromocytoma was confirmed (Normetanephrines 2725.4 mcg/24h, n: 0-600 mcg/24h and Metanephrines 1550 mcg/24h, n: 0-350 mcg/24h). Considering the described adrenal lesion with biochemical behavior, the possibility of ectopic ACTH production from pheochromocytoma was studied. Therefore, ketoconazole 200mg every 8 hours was initiated for hypercortisolism control and adrenergic blockade protocol as pre-surgical preparation for adrenalectomy. Potassium levels (4.48 mEq/L, n: 3.5-5 mEq/L) and glucose levels (93 mg/dL, n: 70-100 mg/dL) normalized after the procedure. Pathology and immunohistochemistry confirmed the diagnosis of an ACTH-producing pheochromocytoma. Conclusion: Pheochromocytoma is a rare cause of ectopic ACTH secretion where pre-surgical management of catecholamine excess and hypercortisolism is crucial, and adrenalectomy is often curative. Reference: (1) Elliott PF, Berhane T, Ragnarsson O, Falhammar H. Ectopic ACTH- and/or CRH-Producing Pheochromocytomas. J Clin Endocrinol Metab 2021;106:598-608. Presentation: 6/1/2024

Cutoff Values of Aldosterone and the Aldosterone-Renin Ratio for Predicting Primary Aldosteronism in Patients with Resistant Hypertension: A Real-Life Study.

Primary aldosteronism (PA) is commonly associated with resistant hypertension. Biochemical tests can be clinically useful in the screening and diagnosis of primary aldosteronism. This study aimed to identify the cutoff values of aldosterone levels (A) and the aldosterone-renin ratio (ARR) for an accurate prediction of PA in patients with apparent resistant hypertension in a real-life scenario. This database-based study included a historical cohort of male and female patients with apparent resistant hypertension, aged 18 years or older and surveyed for PA in a specialized center from 2008 to 2018. Aldosterone and plasma renin activity (PRA) or the plasma renin concentration (PRC) were measured in the treated hypertensive patients. The patients with positive screening results were subsequently referred to the endocrinology department for confirmatory tests. The patients with confirmed PA were included in the case group, and the others remained as controls. Receiver-operating characteristic (ROC) curves were used to identify the cutoff points for aldosterone and the ARR, thereby analyzing their sensitivity and specificity for confirmed PA. Among the 3464 patients (59 ± 13 years old, 41% male) who had apparent resistance hypertension screened, PA was confirmed in 276 individuals (8%). A ≥ 16.95 ng/dL (95% CI: 0.908-0.933) had an odds ratio of 6.24 for PA, while A/PRA ≥ 29.88 (95% CI: 0.942-0.984) or an A/PRC ≥ 2.44 (95% CI: 0.978-0.990) had an odds ratio of 216.17 for PA diagnoses. Our findings suggest that a positive PA screening with aldosterone ≥ 17 ng/dL associated with A/PRA ≥ 29.88 or an A/PRC ratio of ≥2.44 should be sufficient to confirm the diagnosis of PA without confirmatory testing.

Abstract 19: Effect of the endothelin receptor antagonist aprocitentan on plasma endothelin, renin and aldosterone concentrations in patients with resistant hypertension. A biomarker analysis of the PRECISION study.

Hypothesis: Dual endothelin (ET) ET A /ET B receptor antagonist aprocitentan significantly reduced blood pressure in patients with resistant hypertension, who were still hypertensive despite standard background anti-hypertensive drugs including a diuretic, an ARB and a CCB (PRECISION trial, NCT03541174). The effect of aprocitentan in this population, characterized with low renin and elevated aldosterone levels, was assessed on a panel of plasma biomarkers: ET-1, CT-proET-1 (a stable peptide and biomarker for ET-1 production), renin, aldosterone. Methods: From the 730 randomized patients in PRECISION, ET-1 (n=700), CT-proET-1 (n=100, randomly selected), immunoreactive renin (n=679) and aldosterone (n=703) were measured in plasma samples collected at randomization (baseline) and after 4 weeks for either placebo, aprocitentan 12.5 or 25 mg. Results: Four-week placebo treatment had no effect on the studied biomarkers compared to baseline. Treatment with aprocitentan 12.5 and 25 mg increased plasma ET-1 by +34% and +53% and CT-proET-1 by +38% and +47% vs. baseline respectively. Aprocitentan had no effect on renin levels (p>0.05) while decreasing plasma aldosterone by -17% and -24% at the 12.5 and 25 mg dose respectively. Importantly, the reduction in aldosterone did not result in a change in kalemia (see Table ). Conclusions: Aprocitentan caused reactive dose-dependent increases in plasma CT-proET-1 and ET-1, resulting from effective ET receptor blockade. The increase in CT-proET-1 may indicate a compensatory increase in ET-1 de novo synthesis, while the increase in ET-1 may reflect a reduced clearance due to blockade of ET B and increased production. The decrease of aldosterone by aprocitentan confirms the secretagogue role of ET-1 on aldosterone production by adrenal cortical cells via both ET A and ET B receptors This decrease of aldosterone was observed on top of the known decrease induced by an ARB but did not induce hyperkalemia nor aggravation of renal function.

O99 RELATIONSHIP BETWEEN RENIN, ALDOSTERONE, ALDOSTERONE-TO-RENIN RATIO AND LEFT VENTRICULAR MASS INDEX IN YOUNG ADULTS

Background and Objective: Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, based on studies primarily conducted in middle-aged and elderly populations. It is unclear if the biomarkers of PA, including renin, aldosterone, and aldosterone-to-renin ratio (ARR), are associated with left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases, in young adults. Methods: The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27 years. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and females who were on oral contraception were excluded. LVMI was measured by cardiac magnetic resonance imaging. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results: Of 758 participants, 252 (33.2%) were females. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m2; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusions: An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function.

Sex-Specific Associations of Aldosterone and Renin with Body Composition: A Population-Based Cohort Study.

Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood. To investigate the associations of aldosterone and renin with body composition according to sex in the general population. Population-based cohort study. Québec (Canada). Adults aged 40-69 years enrolled to CARTaGENE between 2009 and 2010 (N=3,687). Plasma aldosterone and renin concentrations. Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes). The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (p<0.05). Aldosterone (p=0.02), but not renin (p=0.43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (p<0.05), but not aldosterone (p≥0.05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (p<0.05) but were not associated with lean body mass or muscle mass (p≥0.05). All aforementioned associations were independent of body weight. Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Evaluation of aldosterone to direct renin ratio, low renin and related Phenotypes in Afro-Colombian patients with apparent treatment resistant hypertension

Apparent resistant hypertension (aTRH) is a significant public health issue. Once low adherence to antihypertensive treatment has been ruled out and true resistant hypertension is diagnosed, aldosterone-direct-renin-ratio (ADRR) aids in the screening of an aldosterone-producing adenoma (APA) and primary aldosteronism (PA). Once PA and other secondary causes have been ruled out, the values of aldosterone and renin allow patients to be classified into phenotypes such as low renin hypertension (LRH), Liddle’s-like (LLph), and primary hyperaldosteronism (PAph). These classifications could aid in the treatment decision-making process. However, optimal cut-off points for these classifications remain uncertain. This study aims to assess the prevalence of these phenotypes and the behavior of different cut-offs of the ADRR in an Afro-Colombian population with apparent resistant hypertension, as well to describe their sodium consumption. Afro-descendant individuals 18 years of age or older, diagnosed with resistant hypertension and attending to a primary care center in Colombia were recruited as volunteers. As part of the study, their plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured. The phenotypes were categorized into three groups based on multiple cut-off points from different authors: low renin and low aldosterone phenotype (LLph), low renin and high aldosterone phenotype (PAph), and high renin and high aldosterone phenotype, referred to as the renal phenotype (Rph). The prevalence of ADRR values exceeding the cut-off and phenotypes were calculated. A linear regression model was derived to assess the effect of sodium consumption with PAC, PRC and ADRR. A total of 88 patients with aTRH were included. Adherence to at least 3 antihypertensive medications was 62.5%. The median age was 56 years (IQR 48–60), 44% were female, and 20% had diabetes. The study found that the prevalence of ADRR values exceeding the cut-off ranged from 4.5 to 23%, while low-renin hypertension (LRH) varied from 15 to 74%, Rph was found in approximately 30 to 34% of patients, PAph in 30 to 51%, and the LLph in 15 to 41%, respectively, depending on the specific cut-off value by different authors. Notably, sodium consumption was associated with lower aldosterone (β − 0.15, 95% CI [− 0.27, − 0.03]) and renin concentrations (β − 0.75, 95% CI [− 1.5, − 0.02]), but ADRR showed no significant association with sodium consumption. There were no significant differences in prevalences between the groups taking < 3 vs ≥ 3 antihypertensive medications. Altered aldosterone-direct-renin-ratio, low renin hypertension, Liddle’s-like, and primary hyperaldosteronism are prevalent phenotypes in patients within Afro-Colombian patients with apparent treatment-Resistant hypertension.

Kinetics of Renin Concentrations in Infants Undergoing Congenital Cardiac Surgery.

Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24 h after initiation of CPB. Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4 h after CPB. There was a significant difference in preoperative and 4 h post-CPB renin concentration (4 h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P < .001). Median renin concentration at 24 h after CPB was lower than the preoperative baseline. We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes.

Plasma renin concentration throughout healthy and hypertensive pregnancy: a systematic review and meta-analysis

Plasma renin concentration throughout healthy and hypertensive pregnancy: a systematic review and meta-analysis

Diagnostic Accuracy of Plasma Renin Concentration and Renin Activity in Predicting Mortality and Kidney Outcomes in Patients With Septic Shock and Hypoperfusion or Hypotension: A Multicenter, Prospective, Observational Study.

Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension. This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis. The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively (P=0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration (P=0.044). Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.

SGLT2 Inhibitors Correct Fluid Overload in Adult Kidney Transplant Recipients-A Prospective Observational Study.

In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1week and 1, 3, and 6months. Estimated glomerular filtration rate (eGFR) decreased by -2mL/min/1.73m2 (IQR -10-0) after 1week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1week and correlated with eGFR (r2 = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r2 = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.

Indicaciones e interpretación de los estudios analíticos hormonales de la corteza suprarrenal

In the adrenal cortex, entities ranging from benign diseases such as adrenocortical adenomas to malignant diseases such as adrenocortical carcinoma or adrenal metastases can be found. Regarding functionality, the spectrum of diseases varies widely: from non-functioning adenomas, patients with autonomous cortisol secretion (ACS), primary hyperaldosteronism (PHA), ACTH-independent Cushing's syndrome, excess secretion of sex hormones, congenital adrenal hyperplasia (CAH), and adrenal insufficiency (AI). A hormonal study is essential for the proper characterization of these disorders. Baseline hormonal tests and functional studies are both necessary in some cases to reach the definitive diagnosis. The test of choice for Cushing's syndrome screening is urinary free cortisol, late-night salivary cortisol, or a 1mg dexamethasone suppression test (DST). For ACS, it is a DST. For PAH, it is calculation of the plasma aldosterone concentration and renin activity or concentration ratio. For AI, it is the determination of plasma cortisol between 8:00 and 9:00 a.m. and after cosyntropin stimulation. Lastly, for CAH, it is the measurement of plasma 17-hydroxyprogesterone.

#1437 Renal expression pattern of the relaxin receptor, RXFP1, and effects of the RXFP1 agonist, AZD5462, on renin in non-human primates and humans

Abstract Background and Aims RXFP1 is a G protein-coupled receptor (GPCR) for the pregnancy hormone, relaxin. While preclinical studies, performed primarily in rodent, describe beneficial effects of this pleiotropic peptide across several organ systems, there has been a disappointing lack of success in translating these observations into clinical benefit. To provide a potential pharmacological explanation accounting for this translational gap, the aim of this study was thus to thoroughly evaluate RXFP1 expression across species and tissues as well as to evaluate the renal-intrinsic effects of the RXFP1 agonist, AZD5462. Method Unbiased bioinformatic analysis of several gene expression databases was used as a first approach to compare RXFP1 tissue-level expression between rodent and human. Experimental validation was subsequently performed using scRNAseq, RNAscope and immunohistochemistry on mouse, rat, non-human primate (NHP) and human kidney. The putative renal target engagement effects of RXFP1 agonism were assessed by determining the acute and chronic effects of the RXFP1-selective small molecule agonist, AZD5462, on plasma renin concentrations in both NHPs and in a Phase 1 randomized, single-blind, placebo-controlled study in healthy humans. Results RXFP1 was identified as one of the most highly expressed GPCRs in human and NHP kidney glomeruli. Specifically, by multiple assays, we identified glomerular endothelial cells as the principal cell type expressing RXFP1. This observation is in stark contrast to mouse and rat kidney, where RXFP1 was not readily detected. AZD5462 administered orally to NHPs and healthy human participants elicited an early and sustained dose-dependent increase in plasma renin concentration, and in humans an additional decline in serum creatinine. Conclusion Human RXFP1 kidney glomerular expression is conserved with NHPs but not rodent, thus highlighting the translational and pharmacological challenges in studying RXFP1/relaxin biology across species. The concordant ability of AZD5462 to induce elevations in renin and reduction in serum creatinine, together with relaxin's reported renal-hemodynamic activity in humans, may underlie a previously unappreciated renal-intrinsic RXFP1 target engagement mechanism driving its hemodynamic and renal effects. The potential therapeutic benefits of RXFP1 agonism are the subject of on-going clinical trials in heart failure patients.

Hemp seed protein and its hydrolysate compared with casein protein consumption in adults with hypertension: a double-blind crossover study

BackgroundThe effects of consuming hemp seed protein (HSP) as well as its hydrolysate-derived bioactive peptide (HSP+) on blood pressure (BP) has not, to our knowledge, been investigated in humans. ObjectivesWe aimed to investigate how consumption of HSP and its hydrolysate modulates 24-h systolic (SBP) and diastolic BP (DBP) and plasma biomarkers of BP compared with casein. MethodsIn a double-blind, randomized, crossover design trial, 35 adults who had mild hypertension with SBP between 130 and 160 mmHg and DBP ≤110 mmHg were recruited. Participants were randomly assigned to varying sequences of 3 6-wk treatments, 50 g casein/d, 50 g HSP/d, or 45 g HSP plus 5 g HSP-derived bioactive peptides/d (HSP+), separated by a 2-wk washout period. Treatment effects were assessed with a linear mixed model with repeated measures. ResultsCompared with casein, after HSP+ consumption, 24-h SBP and 24-h DBP decreased from 135.1 and 80.0 mmHg to 128.1 ± 1.6 (P < 0.0001) and 76.0 ± 1.4 mmHg (P < 0.0001), respectively, whereas these values were 133.5 ± 1.6 and 78.9 ± 1.4 mmHg after HSP consumption (P < 0.0001). There were no differences between the HSP and HSP+ consumption in plasma angiotensin-converting enzyme (ACE) activity, renin, or nitric oxide (NO) concentrations. However, these 2 treatments were able to lower both ACE and renin activities and raise NO concentration in plasma compared with casein. ConclusionsThese results suggest that hemp protein consumption, as well as in combination with bioactive peptides, may have a role in the dietary management of hypertension.This trial was registered at clinicaltrials.gov as NCT03508895.

Association of Aldosterone, Renin, and Aldosterone to Renin Ratio with Metabolic Profile in Primary Aldosteronism.

This study aimed to investigate the glycometabolism, fat mass, and lean mass in primary aldosteronism (PA) during disease progression. Patients diagnosed with PA and healthy controls (HCs) were enrolled. A flash glucose monitoring system (FGMS) and dual-energy X-ray absorptiometry (DEXA) were used to measure glucose variability and glucose target rate along with fat mass and lean mass. Comparative analysis of FGMS- or DEXA-derived parameters along with correlation analyses between these parameters and PA progression were performed. Increased glucose variability and poor glucose target rate, along with an increased proportion of truncal fat mass, and decreased proportion of appendicular lean mass, were identified in PA group compared to those in HCs. Plasma aldosterone concentration was positively correlated with glucose variability and poor glucose target rate. Plasma renin concentration was positively correlated with the proportion of truncal fat mass and lean mass, and negatively correlated with the proportion of appendicular fat mass. Aldosterone-to-renin ratio was negatively correlated with the proportion of truncal fat mass and lean mass, and positively correlated with the proportion of appendicular fat mass. Patients with PA presented significant differences in glycometabolism, fat mass, and lean mass compared with HCs, and these alterations correlated with PA progression.

Apelin-13: a novel approach to suppressing renin production in RVHT.

Renovascular hypertension (RVHT) is characterized by renal artery stenosis and overactivated renin-angiotensin system (RAS). Apelin, known for its negative modulation of RAS, has protective effects against cardiovascular diseases. The role and mechanisms of the primary active form of apelin, apelin-13, in RVHT are unclear. In this study, male Sprague-Dawley rats were divided into control, two-kidney one-clip (2K1C) model, and 2K1C with apelin-13 treatment groups. Renin expression was analyzed using immunohistochemistry and molecular techniques. Full-length (pro)renin receptor (fPRR) and soluble PRR (sPRR) levels were assessed via Western blotting, and cAMP levels were measured using ELISA. Plasma renin content, plasma renin activity (PRA), angiotensin II (ANG II), and sPRR levels were determined by ELISA. Human Calu-6 and mouse As4.1 cells were used to investigate renin production mechanisms. The 2K1C model exhibited increased systolic blood pressure, plasma renin content, PRA, sPRR, and ANG II levels, while apelin-13 treatment reduced these elevations. Apelin-13 inhibited cAMP production, renin mRNA expression, protein synthesis, and PRR/sPRR protein expression in renal tissue. In Calu-6 cells, cAMP-induced fPRR and site-1 protease (S1P)-derived sPRR expression, which was blocked by cAMP-responsive element-binding protein (CREB) inhibition. Apelin-13 suppressed cAMP elevation, CREB phosphorylation, fPRR/sPRR protein expression, and renin production. Recombinant sPRR (sPRR-His) stimulated renin production, which was inhibited by the PRR decoy peptide PRO20 and S1P inhibitor PF429242. These findings suggest that apelin-13 inhibits plasma renin expression through the cAMP/PKA/sPRR pathway, providing a potential therapeutic approach for RVHT. Understanding the regulation of renin production is crucial for developing effective treatments.NEW & NOTEWORTHY Our research elucidated that apelin-13 inhibits renin production through the cAMP/PKA/soluble (pro)renin receptor pathway, presenting a promising therapeutic approach for renovascular hypertension (RVHT) by targeting renin expression mechanisms. These findings underscore the potential of apelin-13 as a novel strategy to address RVHT.

Effects of Beraprost with or without NOS Inhibition on Plasma Aldosterone and Hemodynamics in Healthy Cats.

The aim of the study was to evaluate the hemodynamic and RA system effects of the oral administration of the clinical dose of beraprost for feline CKD in healthy cats, and also to examine whether NOS inhibition reversed them. A placebo-controlled pharmacological sequential design study was carried out to assess the plasma aldosterone and renin concentrations (PAC and PRC), blood pressure, heart rate, and exploratorily to estimate renal plasma flow (RPF) and renal vascular resistance (RVR) with simplified methods. Beraprost reduced PAC when compared to the placebo (p < 0.05); this was reversed when NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was added to the beraprost treatment (p < 0.01). No differences in the PRC or hemodynamic parameters were detected between beraprost and the placebo. The correlation ratios (η2) showed opposite relationships between beraprost and the added L-NAME effects on PAC, mean blood pressure (MBP), heart rate, estimated RPF (p < 0.001), estimated RVR (p < 0.01), and PRC (p < 0.05). In healthy cats, the clinical dose of beraprost suppresses PAC, which can be reversed by the inhibition of NOS.

Use of renin versus lactic acid as tissue perfusion biomarkers for mortality prediction in hypotensive critically Ill patients

ABSTRACT Background Exploring a biomarker with enhanced sensitivity and specificity for tissue perfusion may facilitate the timely identification of circulatory collapse, and enable more precise resuscitation efforts. Objective The objective of this study was to ascertain the correlation between whole blood lactate versus plasma renin concentration being a biomarker of tissue perfusion and predictor of mortality among hypotensive critically ill patients. Methods This prospective, observational cohort study enrolled 84 hypotensive critically ill patients. Plasma renin concentration and blood lactate were measured at enrollment, 24, 48, and 72 hours. The primary outcome is the correlation between the recorded renin, lactate concentrations and mortality rate during hospitalization. Results The mean plasma renin concentration at enrollment was 61.95 pg/ml in survivors, and 104.45 pg/ml in non-survivors (p = <0.001). The non-survivors exhibited a significant boost in plasma renin concentration after 48 and 72 hours, opposed to the survivors (112 vs 40.89, and 106.64 vs 28.85 pg/ml) respectively. There was a significant positive correlation between plasma renin, blood lactate concentrations and patient mortality (r = 0.389 & 0.601) respectively. Conclusion Plasma renin and whole blood lactate had positive correlation to mortality, yet plasma renin revealed superior diagnostic accuracy over blood lactate for mortality prediction in hypotensive critically-ill patients. Trial registration The protocol of this study can be obtained on ClinicalTrials.gov with the id NCT05810415.