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Progres En Urologie : Journal de... Feb 2014A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the... (Review)
Review
INTRODUCTION
A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers.
MATERIAL AND METHOD
We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting.
RESULTS
Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers.
CONCLUSION
Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings.
Topics: Humans; Renin-Angiotensin System; Urologic Neoplasms
PubMed: 24485075
DOI: 10.1016/j.purol.2013.09.010 -
The Cochrane Database of Systematic... Apr 2017Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II.
OBJECTIVES
To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension.To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema).
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work.
SELECTION CRITERIA
We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension.
DATA COLLECTION AND ANALYSIS
This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available.Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs.
MAIN RESULTS
12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias.Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes.Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue.
AUTHORS' CONCLUSIONS
Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.
Topics: Amides; Antihypertensive Agents; Blood Pressure; Diarrhea; Fumarates; Humans; Middle Aged; Randomized Controlled Trials as Topic; Renin
PubMed: 28379619
DOI: 10.1002/14651858.CD007066.pub3 -
BMJ Open May 2019Chronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic kidney disease (CKD) is defined by abnormalities in kidney structure and/or function present for more than 3 months. Worldwide, both the incidence and prevalence rates of CKD are increasing. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance through the kidney. RAAS activation is associated with hypertension, which is directly implicated in causation and progression of CKD. RAAS blockade, using drugs targeting individual RAAS mediators and receptors, has proven to be renoprotective.
OBJECTIVES
To assess genomic variants present within RAAS genes, , , , , and , for association with CKD.
DESIGN AND DATA SOURCES
A systematic review and meta-analysis of observational research was performed to evaluate the RAAS gene polymorphisms in CKD using both PubMed and Web of Science databases with publication date between the inception of each database and 31 December 2018. Eligible articles included case-control studies of a defined kidney disease and included genotype counts.
ELIGIBILITY CRITERIA
Any paper was removed from the analysis if it was not written in English or Spanish, was a non-human study, was a paediatric study, was not a case-control study, did not have a renal disease phenotype, did not include data for the genes, was a gene expression-based study or had a pharmaceutical drug focus.
RESULTS
A total of 3531 studies were identified, 114 of which met the inclusion criteria. Genetic variants reported in at least three independent publications for populations with the same ethnicity were determined and quantitative analyses performed. Three variants returned significant results in populations with different ethnicities at p<0.05: insertion, rs699-T allele and rs5186-A allele; each variant was associated with a reduced risk of CKD development.
CONCLUSIONS
Further biological pathway and functional analyses of the RAAS gene polymorphisms will help define how variation in components of the RAAS pathway contributes to CKD.
Topics: Angiotensinogen; Female; Genotype; Humans; Male; Observational Studies as Topic; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 31048445
DOI: 10.1136/bmjopen-2018-026777 -
Cureus Jul 2022The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys... (Review)
Review
Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review.
The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys produce renin which converts angiotensinogen to angiotensin-1 (AT-I) and angiotensin-converting enzyme (ACE) to angiotensin-II (AT-II). AT-II binds to receptors in the adrenal cortex to release aldosterone. AT-II and aldosterone promote water and salt retention, vascular tone, and myocardial contractility. These physiological changes raise blood pressure and circulation. Reduced renal perfusion pressure sensed by baroreceptors and the sympathetic nervous system's β-adrenergic receptors trigger renin release and RAAS activation. RAAS restores hemodynamic stability in pathological states associated with low perfusion. This adaptive response is important for restoring perfusion and hemodynamic stability, but prolonged RAAS activation has deleterious effects on the cardiovascular system. Long-term mineralocorticoid exposure has been linked to left ventricular hypertrophy (LVH) and remodeling. AT-II activates fibroblasts and cardiac myocytes to promote cardiac remodeling. Blocking RAAS can eliminate the long-term negative effects of RAAS activation. Direct renin inhibitors, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are RAAS blockers. RAAS blockade improves mortality and hospitalization in systolic heart failure and acute myocardial infarction. RAAS blockade has not demonstrated the same benefits in other cardiac populations, such as those with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) causes LVH and asymmetric septal hypertrophy. When the outflow tract gradient exceeds 30 mmHg and is associated with septal hypertrophy, it is known as obstructive HCM. Dyspnea on exertion, syncope, and exertional angina are symptoms of HCM. RAAS activation worsens LVH by increasing blood pressure and by directly affecting cardiac myocytes with AT-II and aldosterone. RAAS blockade reverses myocardial fibrosis and slows HCM progression in animal models. We performed a meta-analysis of randomized clinical trials to further investigate the potential benefit of RAAS blockade in HCM patients. Although our findings included significant results for some of the RAAS blockade agents, these findings were not consistent throughout all the studies. Mavacamten, one of the newest treatments, has shown promising outcomes.
PubMed: 35949750
DOI: 10.7759/cureus.26642 -
Pediatric Nephrology (Berlin, Germany) Oct 2021Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved...
BACKGROUND
Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N).
OBJECTIVE
The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity.
METHODS
A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values.
RESULTS
One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-β-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity.
CONCLUSIONS
Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.
Topics: Area Under Curve; Biomarkers; Child; Humans; IgA Vasculitis; Immunoglobulin A; Kidney Failure, Chronic; Male; Nephritis
PubMed: 33993342
DOI: 10.1007/s00467-021-05107-7 -
Medicine Aug 2022It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is... (Meta-Analysis)
Meta-Analysis
The effect of polymorphisms (M235T and T174M) on the angiotensinogen gene (AGT) in coronary artery disease in the Eastern Asian population: A systematic review and meta-analysis.
BACKGROUND
It is thought that genetic factors may play an important role in the development of coronary artery disease (CAD). Several studies report that AGT polymorphism is implicated in CAD susceptibility, but these results contradict those of the other studies with the associations being unclear in the Eastern Asian population. Therefore, meta-analysis was performed to evaluate this relationship.
METHODS
Publication databases were used to search for eligible relevant studies and valid data were extracted from studies meeting the inclusion criteria. Subsequently, odds ratios (ORs) with 95 % confidence intervals (CIs), were used to assess the strength of the association between AGT polymorphism and CAD risk.
RESULTS
Seven eligible studies published only in English were included in the present meta-analysis. In the Eastern Asian population, CAD susceptibility was shown to be related to AGT M235T under the heterozygote model (OR = 0.19). Stratified analysis indicated there was a significant relationship between AGT M235T and CAD risk in China under allelic (OR = 1.34), dominant (OR = 1.43), and heterozygote (OR = 1.62) models. The results showed that the T174M polymorphism was significantly associated with CAD risk in recessive (OR = 2.28) and homozygote (OR = 2.37) models in the Eastern Asian population.
CONCLUSIONS
In the Eastern Asian population, especially the Chinese, the M235T of AGT is associated with CAD susceptibility. The T174M polymorphisms were associated with CAD risk in the Eastern Asian population.
Topics: Angiotensinogen; Asian People; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 36042680
DOI: 10.1097/MD.0000000000029911 -
Journal of Research in Medical Sciences... Nov 2014The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of... (Review)
Review
BACKGROUND
The renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure, electrolyte and fluid homeostasis. The aim of this systematic review is to assess the association of the RAAS genes with diabetes mellitus (DM) and its complications of retinopathy, neuropathy and cardiovascular disease (CVD).
MATERIALS AND METHODS
The relevant English-language studies were identified using the key words of DM, type 1 diabetes mellitus (T1DM), T2DM, renin angiotensin aldosterone polymorphisms or genotypes and RAAS from the search engines of MEDLINE/PubMed, and Scopus from January 1, 1995 to July 30, 2014. Inclusion criteria for selecting relevant studies were reporting the role of RAAS gene variants in the pathogenesis of T1DM or T2DM, diabetic retinopathy (DR), diabetic neuropathy and cardiovascular complication of DM.
RESULTS
The reviewers identified 204 studies of which 73 were eligible for inclusion in the present systematic review. The review indicates the angiotensinogen (AGT) M235T polymorphism might not affect the risk of DM. The role of angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor gene (AT1R) A1166C polymorphisms in the pathogenesis of DM could not be established. Studies indicate the absence of an association between three polymorphisms of AGT M235T, ACE I/D and AT1R A1166C and DR in DM patients. A protective role for ACE II genotype against diabetic peripheral neuropathy has been suggested. Also, the ACE I/D polymorphism might be associated with the risk of CVD in DM patients.
CONCLUSION
More studies with adequate sample size that investigate the influence of all RAAS gene variants together on the risk of DM and its complications are necessary to provide a more clear picture of the RAAS genes polymorphisms involvement in the pathogenesis of DM and its complications.
PubMed: 25657757
DOI: No ID Found -
Revista Brasileira de Ginecologia E... Jul 2022To describe the effects of combined oral contraceptives (COC) on the renin-angiotensin-aldosterone system (RAAS).
OBJECTIVE
To describe the effects of combined oral contraceptives (COC) on the renin-angiotensin-aldosterone system (RAAS).
DATA SOURCES
This is a systematic review according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), registered in PROSPERO under the ID: CRD42020200019. Searches were performed between August 2020 and December 2021, in the following databases: Medline via Pubmed, Cochrane Central Library, Scientific Electronic Library Online, and Latin American and Caribbean Literature in Health Sciences via Virtual Health Library. The effects of the combined oral contraceptive on plasma renin activity values, plasma renin values, angiotensinogen values- also known as plasma renin substrate- angiotensin, and/or aldosterone values.
STUDY SELECTION
A total of 877 studies were selected and, of these, 10 articles met the eligibility criteria and were included in this review.
DATA COLLECTION
Data were combined through qualitative synthesis and included in a spreadsheet previously prepared by the authors.
DATA SYNTHESIS
The collected samples ranged from 18 to 137 participants, totaling 501 women aged between 18 and 49 years throughout all studies. The studies showed increased activity of plasma renin, plasma renin substrate, angiotensin II, and aldosterone in this population.
CONCLUSION
The findings of this study suggest that the COC promotes greater activation of the RAAS. Supporting the idea that its use is related to an increased risk of cardiovascular events, including systemic arterial hypertension.
Topics: Adolescent; Adult; Aldosterone; Angiotensinogen; Contraceptives, Oral, Combined; Female; Humans; Middle Aged; Renin; Renin-Angiotensin System; Young Adult
PubMed: 35724684
DOI: 10.1055/s-0042-1745790 -
Anatolian Journal of Cardiology Mar 2019M235T polymorphism of the angiotensinogen (AGT) gene has been linked with cardiovascular disease (CVD). The aim of this meta-analysis was to investigate whether combined... (Meta-Analysis)
Meta-Analysis
OBJECTIVE:
M235T polymorphism of the angiotensinogen (AGT) gene has been linked with cardiovascular disease (CVD). The aim of this meta-analysis was to investigate whether combined evidence supports this association.
METHODS:
A systematic search was conducted for studies published up to October 2018 that evaluate the association between AGT M235T polymorphism and risk of CVD. Case–control studies were identified, and the association between AGT M235T polymorphism and CVD risk was assessed using genetic models.
RESULTS:
Thirty-nine comparisons from 38 studies were collected, and a meta-analysis and subgroup analysis was performed based on ethnicity. In the overall population (9225 cases and 8406 controls), the occurrence of CVD was found to be associated with AGT M235T polymorphism in both allelic [T vs. M: odds ratio (OR)=1.16] and recessive (TT vs. MT+MM: OR=1.14) models. In subgroup analyses, a significant association was identified between AGT M235T polymorphism and CVD risk in East Asian subgroups in allelic (T vs. M: OR=1.46), homozygous (TT vs. MM: OR=1.78), dominant (MT+TT vs. MM: OR=1.47), and recessive (TT vs. MT+ MM: OR=1.68) models, but there was no significant association in Caucasian populations.
CONCLUSION:
Among East Asians, the AGT variant M235T is associated with CVD risk. However, current evidence suggests that there is no such association in the Caucasian population.
Topics: Angiotensinogen; Asian People; Cardiovascular Diseases; Case-Control Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic
PubMed: 30930452
DOI: 10.14744/AnatolJCardiol.2019.75282 -
PloS One 2024Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy... (Meta-Analysis)
Meta-Analysis
Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.
Topics: Humans; Renin-Angiotensin System; Risk Factors; Polymorphism, Genetic; Peptidyl-Dipeptidase A; Angiotensinogen; Cardiomyopathies; Receptor, Angiotensin, Type 1
PubMed: 38166133
DOI: 10.1371/journal.pone.0295626