UNASSIGNED: Children with Congenital Adrenal Hyperplasia (CAH) have a higher chance of hypertension. The likelihood of hypertension is higher in CAH children who get fludrocortisone medication and have an over-suppression. Plasma renin activity (PRA) is a sensitive indicator when the fludrocortisone dose is insufficient. The objective of this study is to assess the relationship between plasma renin activity with hypertension in 21-hydroxylase-deficient (21-OHD) CAH children.
UNASSIGNED: This cross-sectional observational analytical study was conducted in 2019 at the Pediatric Endocrinology Outpatient Clinic in Dr. Cipto Mangunkusumo Hospital (RSCM), Jakarta, Indonesia. The subjects were 21-OHD CAH children, aged >6 months to 18 years who had already taken hydrocortisone with or without fludrocortisone for at least 6 months, and were divided into hypertension and non-hypertension groups. The subjects were selected by a consecutive sampling method. Data was analyzed using SPSS software (version 23.0) with unpaired t test analysis and multiple logistic regression test. Statistical significance was achieved if P<0.05.
UNASSIGNED: Forty 21-OHD CAH patients were included, and 20 subjects (50%) had hypertension. A higher incidence of hypertension was found in salt-wasting CAH than in simple virilizing types (59.3% vs 30.8%). There was a significant mean difference in PRA levels between hypertension and non-hypertension groups in salt-wasting patients (P=0.016). A significant difference between the last dose of hydrocortisone with the number of hypertension patients in salt-wasting patients (P=0.032) was found, and low PRA levels showed a 1.09 times higher risk of hypertension.
UNASSIGNED: Children with salt-wasting CAH with low PRA levels had a higher risk of getting hypertension.

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 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by -2 mL/min/1.73 m2 (IQR -10-0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1 week 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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

Vascularization plays a critical role in organ maturation and cell type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture. The resulting human kidney organoids show extensive endothelialization with a cellular identity most closely related to human kidney endothelia. Endothelialized kidney organoids also show increased maturation of nephron structures, an associated fenestrated endothelium with de novo formation of glomerular and venous subtypes, and the emergence of drug-responsive renin expressing cells. The creation of an engineered vascular niche capable of improving kidney organoid maturation and cell type complexity is a significant step forward in the path to clinical translation. Thus, incorporation of an engineered endothelial niche into a previously published kidney organoid protocol allowed the orthogonal differentiation of endothelial and parenchymal cell types, demonstrating the potential for applicability to other basic and translational organoid studies.

Primary aldosteronism, characterized by the dysregulated production of aldosterone from 1 or both adrenal glands, is the most common endocrine cause of hypertension. It confers a high risk of cardiovascular, renal, and metabolic complications that can be ameliorated with targeted medical therapy or surgery. Diagnosis can be achieved with a positive screening test (elevated aldosterone to renin ratio) followed by confirmatory testing (saline, captopril, fludrocortisone, or oral salt challenges) and subtyping (adrenal imaging and adrenal vein sampling). However, the diagnostic pathway may be complicated by interfering medications, intraindividual variations, and concurrent autonomous cortisol secretion. Furthermore, once diagnosed, careful follow-up is needed to ensure that treatment targets are reached and adverse effects, or even recurrence, are promptly addressed. These challenges will be illustrated in a series of case studies drawn from our endocrine hypertension clinic. We will offer guidance on strategies to facilitate an accurate and timely diagnosis of primary aldosteronism together with a discussion of treatment targets which should be achieved for optimal patient outcomes.

UNASSIGNED: Few studies have evaluated the performance of non-drug-adjusted primary aldosteronism (PA) screening. Therefore, we aimed to examine the consistency between PA screening results with and without drug adjustment and to explore the effectiveness of screening without drug adjustment.
UNASSIGNED: This prospective study included 650 consecutive patients with a high risk of incidence PA. Patients who initially screened positive underwent rescreening with drug adjustments and confirmatory tests. Regarding the remaining patients, one of every three consecutive patients underwent rescreening with drug adjustments and confirmatory tests. The changes in aldosterone and renin concentrations were compared between patients with essential hypertension (EH) and those with PA before and after drug adjustment. Sensitivity and specificity were used to assess the diagnostic performance of screening without drug adjustment, using the confirmatory test results as the reference.
UNASSIGNED: We screened 650 patients with hypertension for PA. Forty-nine patients were diagnosed with PA and 195 with EH. Regarding drugs, 519 patients were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or diuretics alone or in combination. Forty-one patients were taking beta-blockers. Ninety patients were taking beta-blockers in combination with other drugs. In patients treated with ACEIs, ARBs, CCBs, or diuretics alone, or in combination, or beta-blockers alone, PA positivity was determined using the criteria, aldosterone-to-renin ratio (ARR) >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, and negativity, using the criteria, ARR <9 pg/mL/pg/mL; the sensitivity and specificity were 94.7% and 94.5%, respectively. After drug adjustment, the sensitivity and specificity of screening were 92.1% and 89%, respectively.
UNASSIGNED: In patients not treated with beta-blockers combined with others, when ARR >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, or, ARR <9 pg/mL/pg/mL, non-drug-adjusted screening results were identical to with drug adjustment. Non-drug-adjusted screening could reduce the chance of medication adjustment, enable patients to continue their treatments and avoiding adverse effects, is of clinical importance.
Primary aldosteronism (PA) is the most common form of endocrine hypertension. The risk of stroke, myocardial infarction, heart failure, atrial fibrillation, and deterioration of kidney function is higher in PA than in essential hypertension (EH), even with the same blood pressure (BP) levels. However, many patients remain undiagnosed because most antihypertensive drugs substantially interfere with PA screening results, which makes drug adjustment necessary. This can be a time-consuming and unsafe process, requiring 4–6 weeks, and could lead to a hypertensive crisis and other complications. Some studies have suggested that certain antihypertensive drugs can be continued during PR screening. However, few studies have evaluated the performance of non-drug-adjusted PA screening. Therefore, in this prospective study, we aimed to compare patients with hypertension and a high risk of PA before and after drug adjustment and to use confirmatory test results as a reference to explore the diagnostic or exclusion effect. We found that non-drug-adjusted screening performs similarly to drug-adjusted screening in a particular group of patients. Our findings could aid in preventing unnecessary drug adjustment for PA screening, thereby reducing the risk in these patients.

BACKGROUND: The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro.
METHODS: Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose-response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined.
RESULTS: Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays.
CONCLUSIONS: Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.

In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin-angiotensin system (RAS). Comparative analysis showed that the ethyl acetate fractions, particularly from the Cheongil and Daeshim cultivars, contained the highest levels of polyphenols and flavonoids, with concentrations reaching 110 mg gallic acid equivalent (GE)/g and 471 mg catechin equivalent (CE)/g of extract, respectively. The ethyl acetate fraction showed superior angiotensin-converting enzyme (ACE) inhibitory activity, mainly because of the presence of the prenylated flavonoids kuwanon G and H. UPLC/Q-TOF-MS analysis identified kuwanon G and H as the primary active components, which significantly contributed to the pharmacological efficacy of the extract. In vivo testing of mice fed a high-salt diet showed that the ethyl acetate fraction substantially reduced the heart weight and lowered the serum renin and angiotensinogen levels by 34% and 25%, respectively, highlighting its potential to modulate the RAS. These results suggested that the ethyl acetate fraction of mulberry root bark is a promising candidate for the development of natural ACE inhibitors. This finding has significant implications for the management of hypertension through RAS regulation and the promotion of cardiovascular health in the functional food industry.

UNASSIGNED: This study aimed to investigate the glycometabolism, fat mass, and lean mass in primary aldosteronism (PA) during disease progression.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Patients with PA presented significant differences in glycometabolism, fat mass, and lean mass compared with HCs, and these alterations correlated with PA progression.

The renin-angiotensin system (RAS) constitutes one of the principal mechanisms to maintain hemodynamic and fluid homeostasis. However, most research until now on RAS primarily focuses on its relationship with hypertension and its role in critically ill hypotensive populations is not well understood. With the approval of angiotensin II (Ang II) in the United States and Europe, following a phase 3 randomized controlled trial showing efficacy in catecholamine-resistant vasodilatory shock, there is growing interest in RAS in critically ill patients. Among the fundamental components of RAS, renin acts as the initial stimulus for the entire system. In the context of hypotension, its release increases in response to low blood pressure sensed by renal baroreceptors and attenuated negative Ang II feedback loop. Thus, elevated renin could reflect disease severity and predict poor outcomes. Studies investigating this hypothesis have validated the prognostic accuracy of renin in various critically ill populations, with several reports indicating its superiority to lactate for mortality prediction. Accordingly, renin reduction has been used to assess the effectiveness of Ang II administration. Furthermore, renin holds potential to identify patients who might benefit from Ang II treatment, potentially paving the way for personalized vasopressor management. Despite these promising data, most available evidence is derived from retrospective analysis and necessitates prospective confirmation. The absence of a rapid, point-of-care and reliable renin assay presents another hurdle to its integration into routine clinical practice. This narrative review aims to describe the current understanding and future directions of renin as a biomarker during resuscitation of critically ill patients.