Renin Aldosterone Angiotensin System Research Articles

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2.

APN01 is a soluble recombinant human angiotensin-converting enzyme 2 (rhACE2), a key player in the renin-aldosterone-angiotensin system (RAAS). In clinical studies, APN01 was administered intravenously only, so far. The aim of this study (ClinicalTrials.gov: NCT05065645) was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled APN01. This was a phase I, double-blind, placebo-controlled, dose-escalation study. Inhalation was conducted via a nebuliser over 15 min in three single ascending dose (SAD) cohorts (n=24) and two multiple ascending dose (MAD) cohorts (n=16: every 12 h for 7 days). Doses in the SAD cohort were 1.25, 2.5 and 5 mg·mL-1; doses in the MAD cohort were 2.5 and 5 mg·mL-1. Safety (including adverse events (AEs), laboratory findings and lung function results), PK and PD data were assessed. In the SAD and MAD cohorts, treatment-related AEs were slightly more frequent in the active treatment group than in the placebo group. AEs were mild to moderate, with no dose-limiting toxicities. No clinically relevant changes in lung function and laboratory results were observed. The mean maximum observed plasma concentration (Cmax) values after single and multiple doses of 5 mg·mL-1 APN01 were 1.88 and 6.61 ng·mL-1, respectively. Among the PD variables, significance was found for ACE2 and angiotensin 1-5. The application of aerosolised APN01 is safe and well tolerated after single and multiple doses. By achieving a high local concentration in the lungs and low systemic bioavailability, inhaled rhACE2 may present a therapeutic option in ACE2-related diseases.

ASSOCIATION BETWEEN VITAMIN D LEVEL AND ESSENTIAL HYPERTENSION

Introduction: There is relationship between vitamin D deficiency and hypertension (HTN). The mechanism causing the development of HTN, the Renin Aldosterone Angiotensin System, was discovered to be strongly inhibited by vitamin D. This study was piloted to assess the role of vitamin D deficiency in the development of essential hypertension (EH). Methods: A total of 50 patients with EH and 50 healthy participants participated in this study. Every participant was subjected to clinical history, physical examination, and other necessary blood testing, electrocardiography, and echocardiography. Results: There was a significant decrease in vitamin D in hypertensive group (20.25±3.28 ng/mL) than normotensive group (38.33±6.89 ng/mL). Vitamin D level was moderately negative correlated with systolic blood pressure (BP) (r – 0.43, p – 0.001), strong negative correlation with diastolic BP (r – 0.76, p<0.001), strong negative correlation with intimal thickness (r – 0.67, p<0.001), and moderate negative correlation with ventricular mass (r – 0.48, p<0.001). Intimal thickness and ventricular mass were significantly higher in patients with EH with low vitamin D than those with normal vitamin D levels. Conclusion: There is a strong inverse relationship between serum vitamin D and HTN. Vitamin D deficiency levels are considered an additional risk factor for cardiovascular morbidity and mortality.

Comparison of Urinary Ace 2 Levels in Individuals with Hypertension and Type 2 Diabetes with Individuals who have Hypertension but not Diabetes

Background: In this investigation, the levels of urine Angiotensin Converting Enzyme(ACE2)in patients with Type 2 diabetes and high blood pressure were evaluated and their results compared in individuals having raised blood pressure but they had normal blood sugar control. Given the growing body of evidence linking ACE 2 insufficiency to the etiology of hypertension in diabetic patients, we hoped to find higher Angiotensin Converting Enzyme2 levels in the urine of hypertensive diabetic patients than in those without diabetes. Aim: As a result, new pathways for the development of antihypertensive medicines aimed at protecting Angiotensin Converting Enzyme2, particularly in diabetic patients, may open up. Methods: Two groups, each with 49 subjects, were created from a population of chosen subjects.Patients with diabetes and hypertension were chosen from the Services Institute of Medical Sciences diabetic clinic and medical wards in Lahore. In the clinics, anthropometric characteristics and blood sugar levels were recorded. In the Physiology Laboratory at University of Health Sciences, blood samples were obtained and maintained in order to evaluate biochemical characteristics. Results: We calculated the median value in each group because the data for urine Angiotensin Converting Enzyme 2 readings was not dispersedevenly. Non-diabetic hypertension participants had a median of 26.47mg/dl, while hypertensivediabetic subjects had a median of 22.86mg/dl. This difference in ACE 2 levels in the urine was statistically significant (p0.05). Non-diabetic, hypertension patients had greater urinary Angiotensin Converting Enzyme 2 levels than diabetic, hypertensive patients. Conclusion: Contrary to our expectations, we were unable to confirm that urine Angiotensin Converting Enzyme 2 readingsare higher in people with high arterial pressure and type 2 diabetes mellitus. This is despite the fact that the current study confirmed that both type 2 diabetes mellitus and hypertension are risk factors for chronic kidney disease. Key words: Renin Aldosterone-Angiotensin System, urinary Angiotensin Converting Enzyme 2 levels, Chronic Kidney Disease

Rapid decrease in eGFR with concomitant use of tyrosine kinase inhibitors and renin-aldosterone-angiotensin system inhibitors in patients with chronic myelogenous leukemia.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). However, TKI-related chronic renal toxicity has been reported, particularly in patients with hypertension. We assessed whether incidental use of specific types of antihypertensive drugs, including renin-aldosterone-angiotensin system inhibitors (RAASis), affects the change in estimated glomerular filtration rate (eGFR) during TKI treatment. We retrospectively analyzed all eGFR measurements during TKI treatment for 142 CML patients at Kyushu University Hospital, estimating the rate of eGFR change using a mixed-effects model. Overall, a significant interaction was found between the type of antihypertensive medication used and the yearly change in eGFR (P < 0.01), with RAASi users exhibiting the most rapid decrease in eGFR (- 5.5%/year). The analysis by TKI used showed that the interaction was significant only in imatinib and bosutinib users (P < 0.01 and P = 0.04, respectively). The yearly rate of eGFR decrease was the most notable in RAASi users, at - 5.7 (- 6.6, - 4.9) and - 10.1 (- 12.3, - 7.9) for imatinib and bosutinib users, respectively. Our findings indicate that eGFR should be carefully monitored in patients taking these TKIs.

Chronic Circadian Disruption Contributes to Excess Aldosterone Production and Loss of Diurnal Electrolyte Excretion

Disruptions in circadian rhythms contribute to a number of cardiometabolic health risks, including kidney disease. While chronic circadian disruption (CCD) has been recognized as a health risk in a number of other organ systems, we do not understand the effects of CCD on kidney function and sodium handling factors. Individuals with CCDs such as rotating shift workers, have an increased incidence of kidney and cardiovascular disease including impaired sodium excretion patterns. We hypothesized that this impaired sodium excretion is due in part to increased activation of the renin‐aldosterone‐angiotensin system (RAAS). We recently observed that CCD interrupts blood pressure, heart rate, and activity rhythms. Male 8‐week‐old C57BL/6J mice were placed under either a normal 12:12 light/dark cycle (control) protocol or a 10:10 light/dark cycle (CCD, T20) protocol, each with ad libitum food and water for 12 weeks. Previous experiments with this model have demonstrated that after 10 weeks the T20 mice did not exhibit a significant difference in mean arterial pressure (MAP) between the light and dark cycles (114±13mmHg during dark cycle, 113±12mmHg during light cycle, p=0.86) as opposed to control animals, who did display a typical circadian pattern in MAP averaging 119±3 mmHg during the dark cycle and 101±2 mmHg during the light cycle (p&gt;0.001). The same pattern persisted in the heart rate (HR) of these animals, with the T20 animals lacking a diurnal variation in HR (537±14 BPM during dark cycle, 526±5 BPM during light cycle, p=0.48), and the control animals maintaining a dark/light period difference (584±11 BPM during dark cycle, 511±4 BPM during light cycle, p=0.001). Prior studies indicate that the circadian timing system controls sodium reabsorption throughout the nephron by effecting aldosterone effects on collecting duct sodium transport systems via the molecular clock. Therefore, aldosterone excretion was assayed in urine from control(n=6) and T20 mice (n=4). Interestingly, T20 animals excreted an order of magnitude more aldosterone than control animals (p&lt;0.015 2‐way ANOVA) and lacked a diurnal variation in aldosterone excretion (115.1±51.5 µg/hr during the dark cycle, 64.1±13.1 µg/hr during the light cycle, p=0.17 dark v. light) and during both dark and light phases (0.080±0.014 µg/hr and 0.012±0.003 µg/hr, respectively, p=0.02 dark v. light). T20 mice also lacked a diurnal variation in sodium (UNaV) and potassium (UKV) excretion as compared to control mice. These results suggest that CCD disrupts diurnal sodium handling, at least in part, by disruptions in the RAAS. We further propose that the loss of blood pressure rhythms may be due to hyperaldosteronism in CCD mice.

Interaction of the renin inhibitor aliskiren with the SARS-CoV-2 main protease: a molecular docking study

The renin protein is an upstream enzymatic regulator of the renin-aldosterone-angiotensin system (RAAS) essential for the maintenance of blood pressure. The angiotensin-converting enzyme-2 (ACE2) is a major component of the RAAS and a cell surface receptor exploited by the SARS-CoV-2 virus to enter host cells. A recent molecular modeling study has revealed that the direct renin peptide inhibitor remikiren can bind to the catalytic site of SARS-CoV-2 main protease (Mpro). By analogy, we postulated that the non-peptidic drug aliskiren, a more potent renin inhibitor than remikiren and a drug routinely used to treat hypertension, may also be able to interact with Mpro. An in silico comparison of the binding of the two compounds to Mpro indicates that aliskiren (ΔE = −75.9 kcal/mol) can form stable complexes with the main viral protease, binding to the active site, as remikiren (ΔE = −83.2 kcal/mol). The comparison with a panoply of 30 references compounds (mainly antiviral drugs) indicated that remikiren is a potent Mpro binder comparable to drugs like glecaprevir and pibrentasvir (ΔE = −96.5 kcal/mol). The energy of interaction (ΔE) of aliskiren with Mpro is about 10% lower than with remikiren, comparable to that calculated with drugs like velpatasvir and sofosbuvir. A model is proposed to define the drug binding site, with the best binders (including remikiren) penetrating deeply into the site, whereas the less potent binders (including aliskiren) interact more superficially with the protein. Communicated by Ramaswamy H. Sarma

IMPACT OF COVID-19 ON MULTIPLE BODY ORGAN FAILURE: A REVIEW

COVID-19 is a highly contagious disease caused by Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2); which is a novel single-stranded positive RNA infection which consist of cytokines that activate the pathogenic systems that cause high respiratory pain condition, and adversely affect on multiple body organ in humans as per their immunity standards to fight against the virus. SARS-CoV-2 enters the host cell through Angiotensin-Converting Enzyme 2 (ACE 2). ACE 2 is a sub-part of the Renin-Aldosterone Angiotensin System (RAAS), intelligently communicated in the body's kidney, heart, lungs, and malignant tissues. The malfunctioning of RAAS in the body leads to hypertension, cardiovascular sicknesses, endocrine system and negatively affects a brain-body communication channel. Treatments on the RAAS structure, 'thiazolidinedione's and smoking, toxemia, kidney, lungs disorder due to the SARS-CoV-2 attack on the host cell and notice the behavioral changes of body organs the arrival of cytokines that causes multi-organ damage. This paper involves the study of the effects of coronavirus disease on multiple body-organ injuries.

ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study.

Coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme (ACE) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 patients with diverse degree of severity (33 asymptomatic or mildly symptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 in hypertensive patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 in dyslipidemic (p<0.05) and type 2 diabetic patients (p< 0.01). The association of G alleles with disease severity was adjusted for age, sex, BMI and number of comorbidities, suggesting that both the metabolic comorbidities and the G allele act synergistically on COVID-19 outcome. Although we did not find a direct association between serum ACE levels and COVID-19 severity, we found higher levels of ACE in the serum of patients with the GG genotype of rs4341 and rs4343 (p<0.05), what could explain the higher susceptibility to develop severe forms of the disease in patients with the GG genotype, in addition to hypertension and dyslipidemia. In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE could be predictive markers of severity of COVID-19 in those patients with hypertension, dyslipidemia or diabetes. The knowledge of these genetic data could contribute to precision management of SARS-CoV-2 infected patients when admitted to hospital.

The Renin-Angiotensin-Aldosterone System and Coronavirus Disease 2019.

The renin–aldosterone–angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and the host's expression of this membrane-bound protein could affect susceptibility to infection. The RAAS is an important regulator of cardiovascular physiology and ACE2 has an essential role. People with hypertension and other traits have shown to have an imbalance in ACE/ACE2 levels and reduced levels of ACE2 could enhance the risk of adverse outcome in patients with COVID-19. It has been hypothesised that the RAAS may mediate the interplay between cardiovascular disease and COVID-19 severity. Evidence shows that antihypertensive drugs that target the RAAS have no significant effect on the risk of infection and disease outcome. Variations in RAAS genes have been associated with the risk of developing hypertension and cardiovascular disease and could partly explain the heterogenous response to SARS-CoV-2 infection. This article explores the interplay between the RAAS and COVID-19, with emphasis on the possible relationship between genetic variations and disease severity.

The Central Role of Fibrinolytic Response in COVID-19-A Hematologist's Perspective.

The novel coronavirus disease (COVID-19) has many characteristics common to those in two other coronavirus acute respiratory diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). They are all highly contagious and have severe pulmonary complications. Clinically, patients with COVID-19 run a rapidly progressive course of an acute respiratory tract infection with fever, sore throat, cough, headache and fatigue, complicated by severe pneumonia often leading to acute respiratory distress syndrome (ARDS). The infection also involves other organs throughout the body. In all three viral illnesses, the fibrinolytic system plays an active role in each phase of the pathogenesis. During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells. Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) are closely linked to the RAAS. In lesions in the lung, kidney and other organs, the two plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA), along with their inhibitor, plasminogen activator 1 (PAI-1), are involved. The altered fibrinolytic balance enables the development of a hypercoagulable state. In this article, evidence for the central role of fibrinolysis is reviewed, and the possible drug targets at multiple sites in the fibrinolytic pathways are discussed.

Impact of COVID-19 on Multiple Body Organ Failure: A Review

COVID-19 is a highly contagious disease caused by Severe Acute Respiratory Syndrome CoronaVirus-2(SARS-CoV-2) which is a novel single-stranded positive RNA infection which consist of cytokines thatactivate the pathogenic systems that cause high respiratory pain condition and adversely effect on multiplebody organ in humans as per their immunity standards to fight against the virus. SARS-CoV-2 enters thehost cell through Angiotensin-Converting Enzyme 2 (ACE 2). ACE 2 is a sub-part of the Renin-AldosteroneAngiotensin System (RAAS) which is intelligently communicated in the kidney, heart, lungs and fatal tissuesof the body. The malfunctioning of RAAS in the body leads to hypertension, cardiovascular sicknesses,endocrine system and also affect negatively a brain body communication channel. Treatments on the RAASstructure, thiazolidinedione’s and smoking, toxaemia, kidney, lungs disorder due to the SARS-CoV-2 attackon the host cell and notice the behavioural changes of body organs on the arrival of cytokines that causesmulti-organ damage. This paper involves the study of the effects of coronavirus disease on multiple bodyorgandamages.

The role of kidney biopsy in diagnosis of preeclampsia in kidney transplant patients

ABSTRACT Objective The aim of this report is to review two patients who developed proteinuria in pregnancy after kidney transplant in order to highlight the importance of maintaining a broad differential and the diagnostic utility of kidney biopsy in this clinical scenario. Methods Two cases of women with kidney transplants who presented with proteinuria in pregnancy are described and the literature is reviewed. Results In both cases, a kidney biopsy allowed for prompt diagnosis and treatment. Conclusion Kidney biopsy should be considered an important diagnostic tool in this clinical scenario. Abbreviations ACE: angiotensin-converting enzyme; ESKD: end-stage kidney disease; FSGS: focal segmental glomerulosclerosis; RAAS: renin aldosterone angiotensin system

Changes in plasma aldosterone level after weight loss by bariatric surgery in morbidly obese patients

BackgroundOveractivation of renin-aldosterone-angiotensin system (RAS) is part of the pathogenesis of obesity-associated hypertension. Evidences have shown that weight loss can result in reduction in blood pressure and RAS. This study was aim to investigate changes of plasma aldosterone concentration (PAC) after bariatric surgery.MethodsA prospective study was done in 14 morbidly obese patients undergoing bariatric surgery. Patients who were taking medications that can interfere with PAC and renin levels were excluded. Collection of blood samples were done at baseline and at 3 and 6-month post-bariatric surgery.ResultsFour out of 14 patients had hypertension at baseline. Mean body mass index (BMI) was 56.7 ± 13.5 kg/m2. PAC were significantly decreased at 3-and 6-month post-bariatric surgery from 14.3 ± 8.0 to 7.5 ± 5.5 [reduction of 36% from baseline (P < 0.01)] and 8.0 ± 6.6 ng/dl [reduction of 32% from baseline (P < 0.05)] respectively. The reduction of PAC at 3-month post-surgery was correlated with the reduction of body weight (r = 0.46, P < 0.05), waist circumference (r = 0.73, P < 0.05) and percent of body fat (r = 0.58, P < 0.05).ConclusionsMaximal reduction of PAC in obese patients underwent bariatric surgery occurred during the first 3 months after bariatric surgery. The reduction of PAC was associated with the reduction of body weight, waist circumference and percent of body fat suggesting the link between RAS and obesity-mediated hypertension.

Genetics of Hypertension in African Americans and Others of African Descent.

Hypertension is the leading cause of cardiovascular disease in the United States, affecting up to one-third of adults. When compared to other ethnic or racial groups in the United States, African Americans and other people of African descent show a higher incidence of hypertension and its related comorbidities; however, the genetics of hypertension in these populations has not been studied adequately. Several genes have been identified to play a role in the genetics of hypertension. They include genes regulating the renin-aldosterone-angiotensin system (RAAS), such as Sodium Channel Epithelial 1 Beta Subunit (SCNN1B), Armadillo Repeat Containing 5 (ARMC5), G Protein-Coupled Receptor Kinase 4 (GRK4), and Calcium Voltage-Gated Channel Subunit Alpha1 D (CACNA1D). In this review, we focus on recent genetic findings available in the public domain for potential differences between African Americans and other populations. We also cover some recent and relevant discoveries in the field of low-renin hypertension from our laboratory at the National Institutes of Health. Understanding the different genetics of hypertension among various groups is essential for effective precision-guided medical therapy of high blood pressure.

Current Opinion for Hypertension in Renal Fibrosis.

Arterial hypertension remains to be a serious problem with considerable morbidity and mortality worldwide in the present age. Hypertension is a major risk factor for cardiovascular diseases such as stroke, myocardial infarction, renal failure, and heart failure. Hypertensive nephropathy is the second leading cause of death in chronic kidney disease (CKD) around the world. Long-time hypertension loading results in renal interstitial fibrosis, which is associated with aberrant activation of renal fibroblasts and excessive generation of extracellular matrix (ECM) proteins. Increasing evidence supported that proteinuria, tubular hypertrophy, oxidative stress, activation of renin-aldosterone-angiotensin system (RAAS), collagen turnover, chronic inflammation, and vasoactive substances synergistically contributed to the pathogenesis of hypertensive renal fibrosis. However, the mechanisms involving the pathogenesis of hypertensive renal fibrosis are complex and not fully understood. Also, the effective clinical therapy to halt or even reverse renal fibrosis in hypertension is still limited. In this chapter, we aimed to provide an overview of the main pathophysiologic and mechanistic features of renal fibrosis under hypertensive state. The completion of the studies in these directions would improve our understanding of renal fibrosis in hypertension and also help us better screen treatment strategies for preventing renal destruction associated with hypertension.

Assessment of Vitamin D Status In Patients With Essential Hypertension

Background: There is close relationship between Vit D deficiency and hypertension. It was found that Vit D is potent inhibitor of Renin Aldosterone Angiotensin System (RAAS) which is the main mechanism responsible for development of hypertension. Aim of The Work: To assess the role of vitamin D deficiency in the development of essential hypertension and aggravation of its vascular complications. Subjects and Methods: This study was conducted on 80 individuals. Individuals were divided into two groups: Group 1: comprising 60 patients with essential hypertension. Group 2: comprising 20 healthy individuals. All individuals included in the study were submitted to: Complete history and physical examinations to evaluate exclusion criteria. Liver and renal function tests, fasting and PP blood glucose, CBC, lipid profile, serum vitamin D (25hydroxycholecalciferol), serum Ca & Ph. Doppler study on carotid artery to assess vascular complications and Echocardiography to assess ventricular mass was done. Results: There was statistically significant decrease (p value <0.05) in vitamin D in patients group in comparison to control group. There was highly statistically significant increase (p value <0.001) in intimal thickness and left ventricular mass in patients with low vitamin D level in comparison to patients with normal vitamin D level. In the patient group, 6 patients (10%) were suffering from vitamin D deficiency while 30 (50%) were suffered from vitamin D insufficiency while 24 (35%) show normal levels of vitamin D. Interestingly, intimal thickness and ventricular mass were significantly higher in patients with essential hypertension with low vitamin D than those with normal vitamin D levels. Conclusions: Vitamin D deficiency occurs in the majority of essential hypertension patients and therefore decreased serum vitamin D levels is considered an additional risk factor for cardiovascular morbidity and mortality.

Protocol of randomized control trial for effectiveness of angiotensin receptor blockers on blood pressure control among euvolemic hypertensive hemodialysis patients.

Introduction:Volume overload and the renin–aldosterone–angiotensin system (RAAS) are 2 major factors contributing to hypertension (HTN) among hemodialysis (HD) patients. Although volume-dependent components of HTN can be corrected by appropriate volume removal, a proportion of HD patients experience elevated blood pressure (BP) despite achieving euvolemic and ideal dry weight.Method and analysis:A single center, prospective, randomized, parallel design, single-blind trial will be conducted in the Malaysian state of Kelantan among postdialysis euvolemic hypertensive patients that are on regular dialysis at least 3 times a week. The primary outcome of the trial will be to note the effectiveness of losartan (RAAS inhibitor) in reducing systolic BP < 140 mm Hg compared to standard non-RAAS-inhibitor antihypertensive therapy. The secondary outcome will be to look at all causes of mortality. A body composition monitor (BCM) will be used to assess postdialysis volume and dry weight. Postdialysis euvolemic patients that have systolic BP > 140 mm Hg will be randomized using Covariate Adaptive Randomization to standard or treatment arm. Participants in the treatment arm will be given 50 mg of losartan once daily except on dialysis days, whereas the standard arm patients will be prescribed non-RAAS antihypertensive agents. The study participants will be followed for a period of 12 months. A Wilcoxon statistical test will be performed to note the difference in BP from baseline up to 12 months using Statistical Package for the Social Sciences (SPSS) 20.Ethical and trial registration:The study protocols are approved from the Ethical and Research Committee of the Universiti Sains Malaysia (USM/JEPeM/15050173). The trial is registered under the Australia New Zealand Clinical Trial Registry (ACTRN12615001322527). The trial was registered on 2/12/2015 and the 1st patient was enrolled on 10/12/2015. The trial was formally initiated on 16/02/2016.Conclusion:Management of HTN among HD patients requires understanding the primary cause of HTN and treating accordingly. The current trial is an attempt to reduce BP among postdialysis euvolemic but hypertensive patients.

Modulating kidney transplant interstitial fibrosis and tubular atrophy: is the RAAS an important target?

In follow-up to a recently published randomized controlled clinical trial, Issa et al. provide evidence that systemic activity and physiological responsiveness of the renin aldosterone angiotensin system (RAAS) are well within normal limits in most kidney recipients during the first 5 years post-transplant. Implications of the results include the need to better understand intra-renal RAAS activity in transplanted kidneys and to identify patients in which the graft-protective effects of RAAS blockade are most relevant.

Editorial: Do We Have Effective Means to Treat Arterial Stiffness and High Central Aortic Blood Pressure in Patients with and without Hypertension?

The reduction or loss of arterial elasticity or distensibility leads to arterial stiffness (AS), which has a substantial predictive value for all-cause and cardiovascular disease (CVD) mortality, as well as for non-fatal CVD events [1]. A plethora of evidence consistently showed the prognostic value of aortic stiffness for fatal and nonfatal CVD events in various populations at different levels of CVD risk, including the general population, elderly subjects and patients with hypertension, type 2 diabetes mellitus (T2DM) and end-stage renal disease (ESRD) [2]. It has been reported that 1-SD increase in pulse wave velocity (PWV) is associated with a 47% increase in the risk for total mortality [95% confidence interval (CI), 1.31-1.64] and a similar 47% increase in the risk for CVD mortality (95% CI, 1.29-1.66) [2].

Baroreflex Stimulation Versus Renal Denervation for Treatment of Hypertension: What Constitutes a Logical Comparison of These Interventions on Atrial Electrophysiology?

The autonomic nervous system is a primary modulator of blood pressure, heart rate and cardiac function, and imbalance of the parasympathetic and sympathetic arms of the autonomic nervous system underlies many forms of cardiovascular pathophysiology1. Heart failure and hypertension are often characterized by an excess of sympathetic nerve activity and elevated plasma catecholamine levels. Elevated catecholamines promote activation of the renin-aldosterone-angiotensin system (RAAS). Pharmacologic efforts to treat autonomic imbalance have primarily focused on the use of beta-adrenergic receptor blockers and RAAS antagonists.