Renin-angiotensin-aldosterone System Activation Research Articles

Characterization of the circulating markers of the renin-angiotensin-aldosterone system in telmisartan- or enalapril-treated dogs with proteinuric chronic kidney disease.

Effects of the renin-angiotensin-aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed. To characterize the RAAS in untreated dogs with pCKD compared to healthy, life-stage- and sex-matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan. Dogs with pCKD (n = 36) and healthy controls (n = 20). Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1-5, and 1-7, and aldosterone, and urinary aldosterone-to-creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models. Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1-5, and 1-7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan- and enalapril-treated pCKD dogs, respectively (both P < .001). Mean (95% confidence interval) percentage change from pretreatment value in serum Ang 1-7 concentration was significantly greater in telmisartan- (753% [489%-1134%]) versus enalapril-treated (149% [69%-268%]) dogs (P < .001). Serum aldosterone decreased with treatment (P = .02 for enalapril, P < .001 for telmisartan), with no difference between groups at day 30. Circulating RAAS activity is higher in dogs with pCKD. Compared with enalapril, treatment with telmisartan caused significantly greater increases in the presumed beneficial peptide Ang 1-7.

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.

Advanced progress of the relationship between renin-angiotensin-aldosterone system inhibitors and cancers.

Hypertension and cancers are the most common causes of death in humans, as well as common co-diseases among elderly population. Studies have shown that hypertension is associated with carcinogenesis. The renin-angiotensin-aldosterone system (RAAS) is a crucial regulatory system of blood pressure, fluid, and electrolyte homeostasis, which plays an essential role in the pathogenesis of hypertension, whose mechanism is relatively clear. Studies have indicated that RAAS also widely exists in cancer tissues of different systems, which can affect the risk of cancers by stimulating cancer angiogenesis, participating in cancer-related oxidative stress, and regulating cancer-related immunity. Therefore, inhibiting RAAS activity seems beneficial to decreasing the risk of cancers. As one of the most commonly used antihypertensive drugs, RAAS inhibitors have been widely used in clinical practice. However, the conclusions of clinical studies on the relationship between RAAS inhibitors and cancers are not entirely consistent, which has been widely concerned by clinicians. The latest findings suggest that while RAAS inhibitors may reduce the risk of digestive cancers, respiratory cancers, urological cancers, gynecological cancers, and skin cancers, ACEIs may increase the risk of lung cancer, endometrial cancer, basal cell carcinoma, and squamous cell carcinoma. This article comprehensively reviews animal experiments, clinical studies, and meta-analyses on the relationship between RAAS inhibitors and cancers, to provide references for related studies in the future.

Systemic hemodynamics and pediatric lung disease: mechanistic links and therapeutic relevance.

Chronic lung disease, also known as bronchopulmonary dysplasia, affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focused on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload, and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin-converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation.NEW & NOTEWORTHY Extremely preterm infants are at a higher risk of developing severe bronchopulmonary dysplasia. In a subset of infants, diuretic and pulmonary vasodilator therapy is ineffective. Recent information points toward systemic hemodynamic disease (systemic arterial stiffness and left ventricular dysfunction) as a contributor via back-pressure changes. Mechanistic links include heightened renin angiotensin aldosterone system activity, inflammation, and oxygen toxicity. Angiotensin-converting enzyme inhibition may be operationally more suited compared with induced pulmonary artery vasodilatation.

Modern approaches to understanding pathogenetic link between arterial hypertension and renal failure from the point of view of evidence based medicine

Background: Renal failure and arterial hypertension are critical global health issues affecting millions worldwide. Hypertension, affecting over 1.13 billion individuals, is a significant risk factor for cardiovascular and renal diseases. Chronic kidney disease (CKD), affecting approximately 10% of the global population, significantly impacts morbidity, mortality, and socioeconomic wellbeing. The reciprocal relationship between hypertension and renal failure exacerbates these conditions, creating a detrimental cycle of worsening health. Methods and Materials: This study employs a comprehensive review of epidemiological data, pathophysiological mechanisms, and evidence-based management strategies. The research focuses on the bidirectional link between arterial hypertension and renal failure, analyzing the shared pathophysiological pathways such as endothelial dysfunction, inflammation, oxidative stress, and the activation of the renin-angiotensin-aldosterone system (RAAS). Data from various clinical trials and epidemiological studies are synthesized to propose effective treatment and management plans. Results: The findings indicate a strong reciprocal correlation between arterial hypertension and renal failure. Hypertension is prevalent in over 85% of CKD patients, and individuals with hypertension have a significantly higher risk of developing CKD. Shared pathophysiological mechanisms, such as endothelial dysfunction, inflammation, oxidative stress, and RAAS activation, contribute to the progression and worsening of both conditions. Effective management requires addressing these common mechanisms through evidence-based treatments like RAAS inhibitors and lifestyle modifications. Conclusion: The study underscores the need for integrated management strategies targeting both arterial hypertension and renal failure. Early detection, prevention, and comprehensive treatment approaches are crucial for mitigating the health and socioeconomic impacts of these interrelated diseases. Future research should focus on novel therapeutic strategies and personalized medicine to improve patient outcomes and reduce the global healthcare burden.

Fluid Restriction for Patients with Heart Failure: Current Evidence and Future Perspectives.

Fluid restriction has long been believed to benefit patients with heart failure by counteracting the activated renin-angiotensin aldosterone system and sympathetic nervous activity. However, its effectiveness remains controversial. In this paper, we summarized the current recommendations and reviewed the scientific evidence on fluid restriction in the setting of both acute decompensated heart failure and compensated heart failure. While a recent meta-analysis demonstrated the beneficial effects of fluid restriction on both all-cause mortality and hospitalization compared to usual care, several weaknesses were identified in the assessment of the methodological quality of the meta-analysis using AMSTAR 2. Further randomized controlled trials with larger sample sizes are needed to elucidate the benefits of fluid restriction for both clinical outcomes and patient-reported outcomes in patients with heart failure.

Epithelial Na + Channel Activation after Bile Duct Ligation with Mineralocorticoid Receptor Blockade.

Sodium and fluid retention in liver disease are classically thought to result from reduced effective circulating volume and stimulation of the renin-angiotensin-aldosterone system (RAAS). However, evidence of fluid retention in patients without RAAS activation suggests the involvement of additional mechanisms. In vitro, bile acids activate the epithelial Na+ channel (ENaC) found in the aldosterone-sensitive distal nephron. If this occurs in vivo, ENaC may become activated in liver disease even with antagonism of aldosterone signaling. To test this, we performed bile duct ligation to induce liver disease and increase circulating bile acids in mice given spironolactone to antagonize aldosterone signaling. We analyzed effects on blood, urine and body composition. We also determined the effects of taurocholic acid, a primary conjugated bile acid elevated in liver disease, on ion fluxes in microperfused rabbit collecting ducts. Bile duct ligation increased benzamil-sensitive natriuresis compared to sham, indicating ENaC activation. These effects were not explained by effects on ENaC expression, cleavage, or localization. Bile duct ligated mice also gained significantly more fluid than sham-operated animals. Blocking ENaC reversed fluid gains in bile duct ligated mice but had no effect in shams. In dissected collecting ducts from rabbits, which express ENaC, taurocholic acid stimulated net Na+ absorption. Our results provide experimental evidence for a novel aldosterone-independent mechanism for sodium and fluid retention in liver disease.

Impact of RAAS Receptors and Membrane-Bound Transporter System in the Left Ventricle during the Long-Term Control of Hypertension.

The Renin-Angiotensin-Aldosterone System (RAAS) has been implicated in systemic and neurogenic hypertension. The infusion of RAAS inhibitors blunted arterial pressure and efficacy of use-dependent synaptic transmission in sympathetic ganglia. The current investigation aims to elucidate the impact of RAAS-mediated receptors on left ventricular cardiomyocytes and the role of the sarcolemma-bound carrier system in the heart of the hypertensive transgene model. A significant increase in mRNA and the protein expression for angiotensin II (AngII) receptor subtype-1 (AT1R) was observed in (mREN2)27 transgenic compared to the normotensive rodents. Concurrently, there was an upregulation in AT1R and a downregulation in the MAS1 proto-oncogene protein receptor as well as the AngII subtype-2 receptor in hypertensive rodents. There were modifications in the expressions of sarcolemma Na+-K+-ATPase, Na+-Ca2+ exchanger, and Sarcoendoplasmic Reticulum Calcium ATPase in the transgenic hypertensive model. These observations suggest chronic RAAS activation led to a shift in receptor balance favoring augmented cardiac contractility and disruption in calcium handling through modifications of membrane-bound carrier proteins and blood pressure. The study provides insight into mechanisms underlying RAAS-mediated cardiac dysfunction and highlights the potential value of targeting the protective arm of AngII in hypertension.

The relationship between adipose tissue RAAS activity and the risk factors of prediabetes in different ethnicities: A protocol for a systematic review and meta-analysis.

The incidence and prevalence of prediabetes has become a global concern. The risk factors of prediabetes, such as insulin resistance, adiposity, lipotoxicity and obesity, in conjunction with the alteration of the renin-angiotensin-aldosterone system (RAAS), have been positively correlated with the high morbidity and mortality rate. Thus, this systematic review seeks to establish the relationship between the risk factors of prediabetes, namely insulin resistance adiposity, lipotoxicity, obesity and the RAAS. Therefore, a synthesis of these risk factors, their clinical indicators and the RAAS components will be compiled in order to establish the association between the RAAS alteration and obesity in prediabetic patients. This protocol for a systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) standards. This will be accomplished by searching clinical Medical Subject Headings categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers will examine all of the findings and select the studies that meet the qualifying criteria. To check for bias, the Downs and Black Checklist will be used, followed by a Review Manager v5. A Forrest plot will be used for the meta-analysis and sensitivity analysis. Furthermore, the strength of the evidence will be assessed utilizing the Grading of Recommendations Assessment, Development, and Evaluation procedure (GRADE). The protocol has been registered with PROSPERO CRD42022320252. This systematic review and meta-analysis will include published randomized clinical trials, observational studies and case-control studies from the years 2000 to 2022.

Natriuretic peptide pathways in heart failure in the context of the analysis of the mechanism of action and potential usages of sacubitril/valsartan

Natriuretic peptide pathways in heart failure in the context of the analysis of the mechanism of action and potential usages of sacubitril/valsartan

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass. This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Primary Role of the Kidney in Pathogenesis of Hypertension.

Previous transplantation studies and the concept of 'nephron underdosing' support the idea that the kidney plays a crucial role in the development of essential hypertension. This suggests that there are genetic factors in the kidney that can either elevate or decrease blood pressure. The kidney normally maintains arterial pressure within a narrow range by employing the mechanism of pressure-natriuresis. Hypertension is induced when the pressure-natriuresis mechanism fails due to both subtle and overt kidney abnormalities. The inheritance of hypertension is believed to be polygenic, and essential hypertension may result from a combination of genetic variants that code for renal tubular sodium transporters or proteins involved in regulatory pathways. The renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the major regulators of renal sodium reabsorption. Hyperactivity of either the RAAS or SNS leads to a rightward shift in the pressure-natriuresis curve. In other words, hypertension is induced when the activity of RAAS and SNS is not suppressed despite increased salt intake. Sodium overload, caused by increased intake and/or reduced renal excretion, not only leads to an expansion of plasma volume but also to an increase in systemic vascular resistance. Endothelial dysfunction is caused by an increased intracellular Na+ concentration, which inhibits endothelial nitric oxide (NO) synthase and reduces NO production. The stiffness of vascular smooth muscle cells is increased by the accumulation of intracellular Na+ and subsequent elevation of cytoplasmic Ca++ concentration. In contrast to the hemodynamic effects of osmotically active Na+, osmotically inactive Na+ stimulates immune cells and produces proinflammatory cytokines, which contribute to hypertension. When this occurs in the gut, the microbiota may become imbalanced, leading to intestinal inflammation and systemic hypertension. In conclusion, the primary cause of hypertension is sodium overload resulting from kidney dysregulation.

The emerging concept of glycocalyx damage as the trigger of heart failure onset and progression

The suppression of adrenergic and renin-angiotensin-aldosterone system (RAAS) activity, exaggerated due to hypoperfusion-related hypoxia and/or sodium retention, is crucial for drugs’ efficacy in heart failure (HF). Both, insufficient oxygenation and excess sodium impair the glycocalyx-dependent microcroperfusion and peripheral metabolism, therefore enhancing the adrenergic and RAAS activity. The local renal and pulmonary RAAS activity and hypoxia increase sodium retention. Interstitial sodium accumulation activates interstitial inflammation and coagulation disorders that further diminish glycocalyx-supported microperfusion and peripheral metabolism. The main trigger of glycocalyx damage in reduced ejection fraction (EF) HF is hypoxia; whereas, in HF preserved EF sodium retention prevails; both stimulate left ventricular (LV) cardiac output (CO), however, impair microperfusion and metabolic heat production. Infrared-dependent, surface-induced flow (SIF) and diamagnetic properties of oxygenated haemoglobin; both improve non-Newtonian blood flow. Therefore, the temperature-driven SIF augments the deoxygenated erythrocytes' flow, while the pulmonary oxygenation of haemoglobin, by diamagnetic properties, enables frictionless erythrocytes’ flow in the oxygenated blood compartments complementing the cardiac function in HF.

Protective Role of Taurine on Rat Offspring Hypertension in the Setting of Maternal Chronic Kidney Disease.

Taurine is a natural antioxidant with antihypertensive properties. Maternal chronic kidney disease (CKD) has an impact on renal programming and increases the risk of offspring hypertension in later life. The underlying mechanisms cover oxidative stress, a dysregulated hydrogen sulfide (H2S) system, dysbiotic gut microbiota, and inappropriate activation of the renin-angiotensin-aldosterone system (RAAS). We investigated whether perinatal taurine administration enables us to prevent high blood pressure (BP) in offspring complicated by maternal CKD. Before mating, CKD was induced through feeding chow containing 0.5% adenine for 3 weeks. Taurine was administered (3% in drinking water) during gestation and lactation. Four groups of male offspring were used (n = 8/group): controls, CKD, taurine-treated control rats, and taurine-treated rats with CKD. Taurine treatment significantly reduced BP in male offspring born to mothers with CKD. The beneficial effects of perinatal taurine treatment were attributed to an augmented H2S pathway, rebalance of aberrant RAAS activation, and gut microbiota alterations. In summary, our results not only deepen our knowledge of the mechanisms underlying maternal CKD-induced offspring hypertension but also afford us the impetus to consider taurine-based intervention as a promising preventive approach for future clinical translation.

Evaluating the effect of vitamin D supplementation on serum levels of 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, parathyroid hormone and renin–angiotensin–aldosterone system: a systematic review and meta-analysis of clinical trials

BackgroundVitamin D, one of the most essential micronutrients, is crucial in various health outcomes. However, previous studies showed conflicting results and uncertainty about vitamin D supplementation's optimal dosage and duration. In this study, we aimed to evaluate the vitamin D supplements efficiency on serum levels of 25-hydroxy vitamin D (25(OH)D), 1,25-dihdroxy vitamin D (1,25(OH)2D), parathyroid hormone (PTH) and renin–angiotensin–aldosterone system (RAAS) in adults.MethodsA systematic analysis of eligible and relevant randomized-controlled trials (RCT) published before April 2023 assessing the effect of vitamin D supplementations applied. The studies were identified by searching several databases, including Pubmed, Scopus, Web of Science, ProQuest, and Cochrane Register of controlled trials.ResultsFive eligible RCTs with 346 participants in the intervention and 352 participants in the control group were assessed in our project. According to the results, there was a substantial change in 25(OH)D (SMD: 2.2, I2: 92.3, 95% Confidence Interval (CI): 1.38–3.02, P-value: 0.048) and 1,25(OH)2D (SMD:1.23, I2: 86.3, 95% CI: 0.01- 2.44, P-value < 0.010) affected by vitamin D intervention. Regarding Parathyroid hormone (PTH), however, vitamin D intervention showed a remarkable decrease (SMD: -0.75, I2: 82.4, 95% CI: (-1.3)—(-0.18), P-value < 0.010). Moreover, sensitivity analysis showed significant publication bias in terms of 25(OH)D.ConclusionVitamin D supplements significantly increase the serum levels of 25(OH)D and 1,25(OH)2D and decrease PTH levels. While some studies reported decreasing effect of vitamin D supplements on RAAS activity, some reported no changes.

Effect of vitamin D receptor genetic polymorphism on the clinical response to angiotensin converting enzyme inhibitors therapy among breast cancer patients with chemotherapy induced cardiomyopathy

Abstract Background Blockade of the renin-angiotensin-aldosterone system (RAAS) is the cornerstone treatment of chemotherapy induced cardiomyopathy (CIC) yet, variability in response to angiotensin converting enzyme inhibitors (ACEIs) acting on the RAAS is well-documented. Vitamin D was found to play a role in regulating RAAS. Previous studies revealed an inverse relationship between levels of vitamin D in serum and RAAS activation. Purpose The current study is primarily to evaluate the association between genetic variants in the vitamin D receptor (VDR) and clinical response to ACEIs among breast cancer patients receiving chemotherapy with CIC. Methods A total of 60 breast cancer patients with CIC (mean ejection fraction 30%) on β-blocker therapy were started on a ACEIs and followed for 6 months. Post-ACEIs-treatment changes in ejection fraction (EF) and serum potassium (K) were evaluated. We genotyped VDR gene polymorphisms including; ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570) variants using TaqMan technique. Stepwise linear regression was performed to identify genetic and clinical factors associated with variability in ACEIs response, with adjustment for all potential confounding covariates. Results BsmI (rs1544410) (CT) heterozygous and TaqI (rs731236) (GA) genotypes had a significant increase in EF (12.8% and 10.8 %, respectively) and serum K (1.1 mEq/L and 0.91 mEq/L respectively); adjusted-p = 0.0001 and 0.004 for ∆EF and adjusted-p = 0.005 and 0.002 for ∆K. In contrast, (AA) homozygous carriers of the ApaI SNP (rs7975232) had a smaller increase in EF (∆EF = 1.2%) and K (∆K = 0.1 mEq/L) compared to (CA) (∆EF = 6.5%, ∆K = 0.73mEq/L) and (CC) (∆EF = 9%, ∆K = 0.9mEq/L) carriers; adjusted-p = 0.003 for ∆EF, adjusted-p = 0.004 for ∆K. Finally, for the FokI SNP (rs2228570), there was no significant change in EF and serum K level. Conclusion The results from this study highlight that BsmI (rs1544410) and TaqI (rs731236) are strong predictors of response to ACEIs therapy in chemotherapy-induced cardiomyopathy (CIC).

Serum Soluble Angiotensin-Converting Enzyme-2 Level and Its Potential Association With The Renin-Angiotensin-Aldosterone System in Non-Hypertensive Iraqi COVID-19 Patients: An Observational Study

Background: The novel coronavirus disease (COVID-19) is caused by Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) which utilizes angiotensin converting enzyme2 (ACE2) to invade the host cells. This membrane-bound peptidase is widely distributed in the body; its activity antagonizes the renin-angiotensin-aldosterone system (RAAS). Once SARS-Cov2 enters the cell, it causes downregulation of ACE2, resulting in the unopposed activation of RAAS. The unregulated activity of the RAAS system can deteriorate the prognosis in COVID-19 patients. A soluble form of ACE2 (sACE2) was reported to have a role in the SARS-Cov2 invasion of the susceptible cells.&#x0D; Aim of the study: This study aims to investigate the potential association of serum levels of sACE2 and RAAS components in severe COVID-19 patients compared to healthy individuals.&#x0D; Methods: Eighty-five participants enrolled in the study were grouped into 45 non-hypertensive severe COVID-19 patients and 40 healthy individuals with comparable age and gender. Serum levels of sACE2, renin, angiotensin 2, and aldosterone by ELISA, and serum potassium level was measured by turbidimetric method.&#x0D; Results: The results showed a significant difference in the serum levels of sACE2 (lower), renin, angiotensin 2, and aldosterone (higher) in COVID-19 patients compared to the control subjects (p-value &lt;0.001; for all.&#x0D; Conclusion: Non-hypertensive severe COVID-19 patients have lower sACE2 and higher RAAS peptide levels, and they can serve as diagnostic markers of severe COVID-19 patients.&#x0D; Recommendations: we recommend a future study with a larger sample size that enrolls COVID-19 patients with different severity levels.&#x0D; Keywords: Aldosterone, Angiotensin, COVID-19, Renin, Soluble angiotensin converting enzyme 2

Hubungan Sindrom Metabolik dengan Penyakit Ginjal Kronis: Literature Review

The prevalence of metabolic syndrome in the world continues to increase every year. Various studies have been conducted to investigate the impacts of metabolic syndrome. Most studies prove that metabolic syndrome is associated with increased risk of progressive decrease in kidney function and developing chronic kidney disease in the future. The aim of this literature review is to analyze the relationship and pathophysiological mechanisms between metabolic syndrome and chronic kidney disease. The result of this review shows there is a significant relationship between metabolic syndrome and chronic kidney disease. The presence of metabolic syndrome increases the risk of developing chronic kidney disease in the future, quicken the decline of kidney function, and increases risk of mortality. Metabolic syndrome triggers excessive production of pro-inflammatory cytokines and activation of RAAS (renin-angiotensin-aldosterone system) that causes chronic kidney disease. To prevent the incidence of chronic kidney disease in the future, it is necessary to do prevention such as control healthy diet and lifestyle so we do not suffer metabolic syndrome. In addition, it is important to control the components of metabolic syndrome suffered along with improving diet and lifestyle to prevent severity of metabolic syndrome.

Low plasma renin activity is associated with “Apparently” idiopathic atrial fibrillation

BackgroundPrevious 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. MethodsThis 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. ResultsThis 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 < 1 ng/ml/h compared to the control group (25.5 % vs. 7.7 %, P = 0.003). PRA < 1 ng/ml/h was the only factor found to be associated with the diagnose of AF in both the univariate model (odds ratio [OR] 4.11, 95 % confidence interval [CI] 1.52–11.11, P = 0.005) and the model adjusted for age and sex (OR 3.98, 95 % CI 1.20–13.25, P = 0.024). A similar pattern was seen with paroxysmal AF. No significant difference in the components of RAAS was observed between 11 patients with the recurrence of AF and 40 without the recurrence at the 1-year follow-up. ConclusionsThis observational study revealed an association between low renin activity and the diagnosis of “apparently” idiopathic AF, particularly paroxysmal AF.

Obesity as a risk factor for chronic kidney disease: a contemporary view on the problem. Review

The review article is devoted to an actual clinical problem of participation of obesity in development and progression of chronic kidney disease (CKD). Some pathogenic links due to which a negative renal effect of obesity is mediated including in particular, dyslipidemia (DLP), endothelial dysfunction (ED) of renal vessels, activation of renin‑angiotensin‑aldosterone system (RAAS), arterial hypertension (AH), a production of adipose tissue mediators with renal injuring properties such as leptin, tumor necrosis factor‑α, interleukines 1,6,8 are discussed. The data about the main factors of progression of renal damage associated with obesity included insulin resistance (IR), hyperinsulinemia, DLP, systemic and renal hemodynamic disorders caused by activation of RAAS (AH, intraglomerular hypertension) are given. The role of metabolic syndrome and its components in pathogenesis of CKD as well as a role of diabetes mellitus (DM) frequently combined with obesity in development of diabetic kidney disease (diabetic nephropathy) is generalized. Among adipokines a special attention in the present review is paid for pathogenic role of leptin and adiponektin in obesity with its conditions promoted renal damage. The participation of resistance to leptin in the pathogenesis of CKD through such links as IR, ED, oxidative stress and inflammation is discussed. The role of ED and glomerular hyperfiltration in pathogenesis of microalbuminuria is elucidated. The significance of injury of kidney tubular cell structures so called podocytes in pathogenesis of CKD in obesity is uncovered. The clinical significance of early revealing of renal pathology as well as body weight, glycemia level, arterial blood pressure control and following of healthy mode of life in reduction of risk development of CKD associated with obesity, DM and other metabolic disorders is generalized. It’s emphasized that evaluation of lipid and carbohydrate exchange parameters, serum leptin level, IR indices is considered to be perspective for diagnostics of renal damage in obesity.