scholarly journals Diabetes and Renin-Angiotensin-Aldosterone System: Pathophysiology and Genetics

2021 ◽  
Author(s):  
A.H.M. Nurun Nabi ◽  
Akio Ebihara
Keyword(s):  
Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Kidney Diseases ◽  
Association Studies ◽  
Plasma Renin ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Genome Wide ◽  
Renal Vascular

Diabetes mellitus (DM) is a metabolic disorder and characterized by hyperglycemia. Being a concern of both the developed and developing world, diabetes is a global health burden and is a major cause of mortality world-wide. The most common is the type 2 diabetes mellitus (T2DM), which is mainly caused by resistance to insulin. Long-term complications of diabetes cause microvascular related problems (eg. nephropathy, neuropathy and retinopathy) along with macrovascular complications (eg. cardiovascular diseases, ischemic heart disease, peripheral vascular disease). Renin-angiotensin-aldosterone system (RAAS) regulates homeostasis of body fluid that in turn, maintains blood pressure. Thus, RAAS plays pivotal role in the pathogenesis of long-term DM complications like cardiovascular diseases and chronic kidney diseases. T2DM is a polygenic disease, and the roles of RAAS components in insulin signaling pathway and insulin resistance have been well documented. Hyperglycemia has been found to be associated with the increased plasma renin activity, arterial pressure and renal vascular resistance. Several studies have reported involvement of single variants within particular genes in initiation and development of T2D using different approaches. This chapter aims to investigate and discuss potential genetic polymorphisms underlying T2D identified through candidate gene studies, genetic linkage studies, genome wide association studies.

scholarly journals The effect of chronic usage of Renin-Angiotensin-Aldosterone System Blocking Agents on Incidence of Contrast-Induced Nephropathy in patients with Diabetes Mellitus and Renal Insufficiency. A Restropesctive Cohort Study

2019 ◽  
Vol 40 (1) ◽  
Author(s):  
Astika Widy Utomo ◽  
Dwi Aris agung Nugrahaningsih ◽  
Iwan Dwiprahasto
Keyword(s):  
Diabetes Mellitus ◽  
Renal Insufficiency ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Contrast Induced Nephropathy ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Blocking Agents ◽  
Patients With Diabetes

Background: This study was to investigate the effect of long term use of Renin-Angiotensin-Aldosterone System(RAAS) blocking agents on the incidence of Contrast-Induced Nephropathy(CIN) on patients with Diabetes Mellitus(DM) and renal insufficiency underwent Percutaneous Coronary Intervention (PCI). Methods:A total 281 of  subjects were included in this study and divided into two groups based on prior use of RAAS blocking agents (RAAS +, n = 146; RAAS -, n = 135). CIN was defined as an increase of ≥25% in creatinin over baseline value 48-72 hours after PCI. Result: Total incidence of CIN was 14,95%. There was no difference in the incidence of CIN between 2 study groups (p = 0,952) and relatif risk for CIN was 1,02. Left Ventricular ejection Fraction (LVEF) ≤ 40 % (OR 2,300; 95% CI 1,028 – 5,143; p = 0,043), anemia (OR 2,628; 95% CI 1,274 – 5,422; p = 0,009) and Glomerular Filtration rate (GFR) pre PCI ≤ 60 mL/menit (OR 2,782; 95% CI 1,293 – 5,987; p = 0,009) were important predictors of CIN. Conclusion: Long term use of RAAS blocking agents do not  increase the incidence of CIN on patients with DM and renal insufficiency underwent PCI.

scholarly journals Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease

2016 ◽  
Vol 310 (10) ◽  
pp. R877-R884 ◽  
Author(s):  
Radko Komers ◽  
Horacio Plotkin
Keyword(s):  
Structural Changes ◽  
Kidney Diseases ◽  
Angiotensin Receptor Blockers ◽  
Experimental Studies ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Stage Renal Disease ◽  
End Stage ◽  
New Treatments

Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients. Inhibition of endothelin (ET) system in combination with established RAASis may represent such an approach. There are complex interactions between both systems and similarities in their renal physiological and pathophysiological actions that provide theoretical rationale for combined inhibition. This view is supported by some experimental studies in models of both diabetic and nondiabetic CKD showing that a combination of RAASis with ET receptor antagonists (ERAs) ameliorate proteinuria, renal structural changes, and molecular markers of glomerulosclerosis, renal fibrosis, or inflammation more effectively than RAASis or ERAs alone. Practically all clinical studies exploring the effects of RAASis and ERAs combination in nephroprotection have thus far applied add-on designs, in which an ERA is added to baseline treatment with ACEIs or ARBs. These studies, conducted mostly in patients with diabetic nephropathy, have shown that ERAs effectively reduce residual proteinuria in patients with baseline RAASis treatment. Long-term studies are currently being conducted to determine whether promising antiproteinuric effects of the dual blockade will be translated in long-term nephroprotection with acceptable safety profile.

scholarly journals The circulating renin-angiotensin-aldosterone system is down-regulated in dogs with glomerular diseases compared to other chronic kidney diseases with low-grade proteinuria

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262121
Author(s):  
Lisa-Maria Grandt ◽  
Ariane Schweighauser ◽  
Alan Kovacevic ◽  
Thierry Francey
Keyword(s):  
Kidney Diseases ◽  
Plasma Renin ◽  
Fractional Excretion ◽  
Fluid Volume ◽  
Volume Status ◽  
Low Grade ◽  
Glomerular Diseases ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin ◽  
Fractional Excretion Of Sodium

Glomerular diseases (GD) lead to a variety of disorders of the vascular and the total body water volumes. Various pathomechanisms, including vascular underfill and overfill, have been suggested to explain these disturbances. Accordingly, the circulating renin-angiotensin-aldosterone system (cRAAS) is expected to be activated as either a cause or a result of these fluid disorders. The aim of this study was to characterize the activity of the cRAAS in dogs with GD and to evaluate its relationship with the vascular volume status. In a prospective study, we evaluated the plasma renin activity and the serum aldosterone concentration in 15 dogs with GD. Their fluid volume status was estimated with clinical variables reflecting volemia and hydration, echocardiographic volume assessment, N-terminal pro B-type natriuretic peptide, blood urea nitrogen:creatinine ratio, and the urinary fractional excretion of sodium. Ten dogs with chronic kidney disease (CKD) with matching degree of azotemia were recruited as controls. The activity of the cRAAS was low in 10 dogs, normal in 3 dogs, high in 1 dog and equivocal (high renin—low aldosterone) in 1 dog with GD. These dogs had a lower cRAAS activity than dogs with CKD (p = 0.01). The clinical evaluation showed 8 hypovolemic and 7 non-hypovolemic dogs; 3 dehydrated, 9 euhydrated and 3 overhydrated dogs. The cRAAS activity was not different between hypovolemic and non-hypovolemic dogs. The down-regulated cRAAS without obvious association with the clinical volume status of these dogs with GD, suggests different mechanisms of fluid volume dysregulation in dogs with GD than previously assumed. This finding however should be confirmed in a focused larger scale study, as it may influence the use of cRAAS blockers as part of the standard therapy of GD in dogs.

scholarly journals Significance of the results of genome-wide association studies for primary prevention of type 2 diabetes mellitus and its complications. Personalised approach

2014 ◽  
Vol 17 (2) ◽  
pp. 10-19 ◽  
Author(s):  
Ivan Ivanovich Dedov ◽  
Olga Mikhailovna Smirnova ◽  
Irina Vladimirovna Kononenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Diseases ◽  
Primary Prevention ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

The method of Genome-Wide Association Studies (GWAS) steadily becomes the basis for searching for candidate genes of monogenic and multifactorial diseases, including type 1 and 2 diabetes mellitus, coronary heart disease, obesity, vascular diseases, and others. To date, approximately 40 loci associated with type 2 diabetes mellitus (T2DM) have been identified and genetic predisposition factors for cardiovascular diseases have been determined. In some cases, the GWAS results not only enable understanding of the pathophysiologic basis for diseases, but also may give rise to new drugs. However, the question naturally arises about the possibility of implementing the accumulated knowledge to predict the development of diseases, including T2DM and its vascular complications. This review summarises the literature data on the possibilities to use the GWAS results to calculate the risk of developing diabetes and cardiovascular diseases. Determination of the individual genetic risk will allow for the primary prevention of diseases and will apparently be the basis of personalised predictive medicine in the near future.

The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

scholarly journals Tactics of antihypertensive therapy during COVID-19 pandemic

2021 ◽  
Vol 93 (9) ◽  
pp. 1125-1131
Author(s):  
Valery I. Podzolkov ◽  
Anna Е. Bragina ◽  
Yulia N. Rodionova ◽  
Galina I. Bragina ◽  
Ekaterina E. Bykova
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Arterial Hypertension ◽  
Ace Inhibitor ◽  
Fixed Combination ◽  
Significant Risk ◽  
Effective Control ◽  
Combination Drug ◽  
Renin Angiotensin Aldosterone System ◽  
Renin Angiotensin

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

Primary Sjögren Syndrome

2015 ◽  
Author(s):  
E. William St. Clair ◽  
Melissa A. Wells
Keyword(s):  
Keratoconjunctivitis Sicca ◽  
Association Studies ◽  
Connective Tissue Diseases ◽  
Lymphocyte Activation ◽  
Genome Wide Association Studies ◽  
Dry Eyes ◽  
Rheumatologic Diseases ◽  
Genome Wide ◽  
Chronic Inflammatory Condition

This review focuses on the primary category of Sjögren syndrome (SS), a chronic inflammatory condition that is defined by the presence of dry eyes (keratoconjunctivitis sicca) or dry mouth (xerostomia) in the absence of other rheumatologic diseases. SS may also have extraglandular manifestations in the form of pulmonary, renal, gastrointestinal, and neurologic diseases that can cause significant morbidity and increased mortality and is distinct from other connective tissue diseases. Although the etiology of primary SS is unknown, genome-wide association studies are continuing to reveal that susceptibility to the disease is based on genetic predisposition; patients with primary SS have been identified with several non–major histocompatibility complex genetic polymorphisms that are statistically associated with increased disease susceptibility. In a recent study, blood CD4+ T cells from patients with primary SS were shown to differ in their patterns of DNA methylation compared with healthy controls and demonstrated that many genes involved in lymphocyte activation and the immune response were poised for transcription. Treatment of primary SS mainly involves relief of symptoms and prevention of long-term disease complications. Although biologic therapies have been studied, the results so far have been either negative or inconclusive. This review contains 5 highly rendered figures, 5 tables, and 89 references.

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