Renin-angiotensin System Blockade Therapy Research Articles

تثبيط جملة الرينين-أنجيوتنسين يحسن الصيغة اللبيدية لدى مرضى الداء الكلوي المزمن

The aim of this study was to evaluate whether the blockade of renin-angiotensin system (RAS), achieved by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), could affect the plasma lipid profile in chronic kidney disease (CKD) patients. Ninety-four hypertensive patients with CKD (stage 3-5) were enrolled. Forty-nine patients were treated with either ACEIs or ARBs daily for 6 months, and forty-five patients were treated with other antihypertensive agents (calcium channel blockers (amlodipine), b blockers, diuretics) as positive control group. Creatinine, estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) levels measurements were performed before and after the six-month treatment. An improvement in serum lipids levels in hypertensive patients with CKD resulted from RAS blocked therapy and other antihypertensive agents. Both treatment groups significantly decreased total cholesterol (TC), by 7.77% in ACEIs/ARBs group (p≤0.01) and 6.42% in other antihypertensive group (p≤0.05). In CKD patients treated with ACEIs/ARBs, levels of TG (3.29%), and LDL-C (3.15%) dropped more than with other antihypertensive medications (2.12%, and 1.19% respectively). RAS blocked therapy significantly increased HDL-C levels in CKD patients by 5.94% (p≤0.05). The results indicate that RAS blockade therapy with ACEIs or ARB positively affects lipid profile, which may improve the cardiovascular risks caused by CKD.

Hypertension and Electrolyte Disorders in Patients with COVID-19.

The worldwide coronavirus disease 2019 (COVID-19) pandemic is still in progress, but much remains unknown about the disease. In this article, we review the association of hypertension or the renin-angiotensin system (RAS) with COVID-19 and the correlation between electrolyte disorders and disease severity. Underlying hypertension is likely to be associated with severe or critical COVID-19, but the relationship is not clear owing to confounding factors. Angiotensin-converting enzyme 2 (ACE2) plays an important role in the non-classical RAS pathway and binds to a receptor binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The RAS blockade is known to increase ACE2 levels, but controversy remains regarding the effect of RAS blockade therapy in the course of COVID-19. Some reports have indicated a protective effect of RAS blockade on COVID-19, whereas others have reported an association of RAS blockade therapy with the occurrence of severe complications such as acute kidney injury and admission to the intensive care unit. Electrolyte disorders are not uncommon in patients with COVID-19, and severe COVID-19 has frequently shown hypokalemia, hyponatremia, and hypocalcemia. Electrolyte imbalances are caused by alteration of RAS, gastrointestinal loss, effects of proinflammatory cytokines, and renal tubular dysfunction by the invasion of SARS-CoV-2.

Renin-angiotensin system blockade after transcatheter aortic valve replacement (TAVR) improves intermediate survival.

Introduction: Hypertension is common in patients with severe aortic stenosis undertaking transcatheter aortic valve replacement (TAVR). Renin–angiotensin system (RAS) blockade therapy with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) has recently been associated with improved outcomes after surgical aortic valve replacement and TAVR, but it is unknown if these findings apply to a more rural patient population. Methods: A retrospective cohort study of 169 patients with at least 1 year of post-TAVR follow-up at a single predominantly rural US center was performed to determine if RAS blockade after TAVR affects short- and long-term outcomes. Seventy-one patients were on an ACEI or ARB at the time of TAVR and at 1 year post-TAVR follow-up. Fisher’s exact test was used for categorical data and t-test/ANOVA was used to determine the statistical significance of continuous variables. Results: In a well-matched cohort, RAS blockade therapy post-TAVR was associated with significantly improved overall survival at 2 years (95% vs. 79%, P = 0.042). RAS blockade was also associated with a trend towards decreased heart failure exacerbations in the first year after TAVR, which was statistically significant in the 30 days to 6 months timeframe after TAVR (8% vs. 21%, P = 0.032). Conclusion: In a rural patient population, RAS blockade after TAVR is associated with improved overall survival and a trend towards decreased heart failure exacerbations. This study builds upon previous studies and suggests that TAVR should be considered a compelling indication for these agents.

TCTAP A-094 The Efficacy of Renin-angiotensin System Blockades on 2-year Outcomes in Coronary Artery Ectasia

Renin-angiotensin system plays a pivotal role in Coronary artery ectasia (CAE), hence the CAE patients might benefit from the renin-angiotensin system blockade (RASB) therapy. Accordingly, this study was designed to investigate the impact of RASB therapy on the outcomes of coronary artery ectasia (

The beneficial effects of renin–angiotensin system blockades on 2 year outcomes in coronary artery ectasia patients

Objectives: This study was designed to investigate the impact of renin–angiotensin system blockade (RASB) therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on the outcomes of coronary artery ectasia (CAE).Methods: The CAE patients identified by coronary angiography from our center were consecutively enrolled. We obtained the baseline discharge prescription of RASB from the medical records system and conducted follow-up through telephone interviews. Cox regression models, propensity score and subgroup analysis were used to assess the impact of RASB on all-cause mortality and non-fatal myocardial infarction. Both the unadjusted and adjusted Kaplan–Meier curves stratified by RASB therapy were plotted.Results: There were 595 patients with CAE in total and 333 (56.0%) were prescribed RASB therapy. Over a 2 year follow-up time, 16 all-cause deaths and 10 non-fatal myocardial infarctions were identified. Those patients treated with RASB had a significantly lower all-cause mortality and non-fatal myocardial infarction rate with an adjusted hazard ratio of 0.32 (95% confidence interval: 0.13 to 0.77, p = .011). The outcome benefits of RASB therapy were further confirmed in the propensity score analysis and subgroup analysis.Conclusions: This observational study suggests that RASB therapy is associated with a lower risk of all-cause mortality and non-fatal myocardial infarction in patients with CAE.

Role of immunosuppressive therapy and predictors of therapeutic effectiveness and renal outcome in IgA nephropathy with proteinuria.

IntroductionThe aim of the study was to analyze the role of immunosuppressive therapy and identify independent predictors of therapeutic effectiveness and outcome in IgA nephropathy (IgAN) patients with proteinuria.Material and methodsTwo hundred and six IgAN patients with proteinuria (1–3.5 g/day) were included between January 2005 and December 2011, and divided into two groups: group A (n = 125), receiving renin-angiotensin system blockade therapy alone; and group B (n = 81), combining the above with immunosuppressive therapy. The clinicopathological features, response and safety were recorded. In univariate and multivariate models, the factors that influence response to therapy and renal outcome, especially pathologic features, were analyzed.ResultsThe patients in group B presented more severe proteinuria and hypoalbuminemia with more severe hematuria (p < 0.05) but no significant difference in the pathologic changes compared with group A. After follow-up, the response rate was higher in group B than in group A (p < 0.001). No pathologic feature or clinical parameter apart from steroid therapy (HR = 0.500, 95% CI: 0.304–0.821, p = 0.006) was strongly associated with therapeutic effectiveness. Endocapillary hypercellularity (HR = 2.849, 95% CI: 1.244–6.524, p = 0.013) seemed to be an independent predictor of poor response to steroid therapy. The renal survival rate was not significantly different between the two groups (p = 0.074). Estimated glomerular filtration rate at baseline may be an independent predictor of renal outcome.ConclusionsSteroid therapy could be an effective therapy in proteinuric IgAN patients, and endocapillary hypercellularity seemed to predict poor response to steroid. Renal function at baseline rather than treatment strategies and pathologic features may be independently associated with renal survival.

Renin-angiotensin system blockade therapy after surgical aortic valve replacement for severe aortic stenosis: a cohort study.

Data are lacking on the effect of renin-angiotensin system (RAS) blockade therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers after surgical aortic valve replacement (SAVR) for severe aortic stenosis (AS). To investigate the association between RAS blockade therapy and outcomes after SAVR for severe AS. Retrospective study. Single tertiary referral care center. Patients who were prescribed angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers after SAVR for severe AS between 1991 and 2010 who had at least 2 refills 90 days apart and at least a 6-month follow-up constituted the RAS blockade group (n=741). Patients who did not receive these prescriptions were in the untreated group (n=1011). Unadjusted and propensity-matched analyses (594 matched pairs of treated and untreated patients) were performed. The primary outcome was survival rates after SAVR. Secondary end points were changes in left ventricular mass index, left ventricular ejection fraction, and left atrial size. Overall unadjusted estimated survival rates at 1, 5, and 10 years were significantly greater in the RAS blockade group than in the non-RAS blockade group (99%, 90%, and 60% vs. 99%, 81%, and 53%, respectively; P<0.001). Among propensity-matched patients, estimated survival rates at 1, 5, and 10 years remained significantly greater in the RAS blockade group than in the non-RAS blockade group (99%, 90%, and 71% vs. 96%, 78%, and 49%, respectively; P<0.001). For the matched cohorts, the groups did not significantly differ in the change in left ventricular mass index (P=0.37), left ventricular ejection fraction (P=0.67), or left atrial size (P=0.43) after SAVR on echocardiographic analysis. Retrospective, single-center analysis. Renin-angiotensin system blockade therapy is associated with increased survival rates in patients after SAVR for severe AS. A randomized trial of RAS blockade therapy after SAVR should be considered. None.

Renin–Angiotensin System Inhibitors Prevent the Recurrence of Atrial Fibrillation

This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed to identify randomized controlled trials involving the prevention of recurrence of AF with renin-angiotensin system blockade therapy. Subgroup analysis and meta-regression were performed. Publication bias was checked through funnel plot and Egger's test. Twenty-one randomized controlled trials including 13,184 patients with AF were identified. Overall, the recurrence of AF was significantly reduced in patients using ACEI/ARBs [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32-0.56; P < 0.00001], especially both in irbesartan subgroup (OR, 0.38; 95% CI, 0.21-0.68; P = 0.001) and in patients receiving antiarrhythmic drug (AAD) (OR, 0.37; 95% CI, 0.29-0.48; P < 0.00001), and there was no significant difference between ACEIs and ARBs (ACEIs: OR, 0.42; 95% CI, 0.31-0.57 and ARBs: OR, 0.42; 95% CI, 0.31-0.57). Moreover, it was found that the benefits of ACEI/ARBs revealed positive correlation to systolic blood pressure (regression coefficient: -0.0700257, P = 0.000) in no-AAD users. ACEI/ARBs are effective on the secondary prevention of AF, especially in patients receiving AAD and suffering from hypertension.

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin-angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10years old during 1996-2009. The recipients were divided into group 1 with RAS blockers (n=40) and group 2 without RAS blockers (n=54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan-Meier estimated death-censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7years, respectively (log rank P=0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33-5.49, P=0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18-0.79, P=0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long-term graft survival among adults transplanted with single pediatric donor kidneys.

Use of low-dose sulodexide in IgA nephropathy patients on renin–angiotensin system blockades

BackgroundDespite using renin–angiotensin system (RAS) blockades, some of the patients with immunoglobulin A (IgA) nephropathy often had persistent proteinuria of more than 500mg/d. They need to be managed further by alternative methods to halt the progression of the disease; these methods could also be applied safely over a long period of time. In this context, sulodexide has been studied for the management of diabetic nephropathy. MethodsA retrospective review was carried out involving 20 patients with IgA nephropathy who had been taking sulodexide (50mg daily) as an add-on therapy together with an optimal dose of RAS blockades during 2008–2009. We evaluated the proteinuria reduction rates and renal function changes. ResultsDuring 11.1±72.7 months of follow-up duration, urinary protein-to-creatinine ratio (UPCR) decreased for 1.57±0.6 to 1.17±0.7 g/g (P=0.032). Twenty-five percent of the patients showed a greater than 50% reduction of UPCR, and 40% had a UPCR of less than 1.0g/g at their final observations. The analysis of the factors contributing to the effect found that a higher pretreatment UPCR showed a significant correlation with the UPCR decrease (r=0.45, P=0.047). Neither the adverse effects nor the renal function impairments were documented during the management. ConclusionLow-dose sulodexide has an additional modest antiproteinuric effect on IgA nephropathy undergoing RAS blockade therapy.

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer

PurposeThe aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin–angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers. MethodsWe fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. ResultsWhen compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth. ConclusionPresent results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment.

Impact of Renin-Angiotensin System Blockade Therapy on Outcome in Aortic Stenosis

The purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling. The Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (>110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations). A total of 2,117 patients with AS (mean age 73 ± 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis. This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

The Role of Renin–Angiotensin System Blockade Therapy in the Prevention of Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

Current evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have emerged as novel drugs for preventing the development of atrial fibrillation (AF). A meta-analysis was performed of 26 randomized controlled clinical trials evaluating the effect of ACEIs or ARBs on the prevention of AF. Overall, ACEIs and ARBs revealed statistically significant preventive effects on AF (odds ratio (OR), 0.65; 95% confidence interval (CI), 0.55-0.76). The preventive effect was similar in the two classes of drugs (ACEI: OR, 0.68; ARB: OR, 0.69). ACEIs and ARBs showed greater preventive effects on recurrent AF (OR, 0.45; 95% CI, 0.31-0.65) than on new-onset AF (OR, 0.80; 95% CI, 0.70-0.92). Prevention was greatest in patients with AF who were receiving amiodarone as a basic treatment drug (OR, 0.35; 95% CI, 0.26-0.48). In patients with heart failure, there appeared to be a large effect (OR, 0.497), but the credible interval (CrI) limits were wide (95% CrI, 0.187-1.161).

Routine renin-angiotensin system blockade in renal transplantation?

There is ample evidence to support the recommendation of renin-angiotensin system blockade therapy as the standard of care for strategies aimed at preserving renal function in chronic renal disease. Nevertheless, despite the well established antihypertensive effects of these drugs, the use of renin-angiotensin system blockers in renal transplantation has been quite limited so far, nephrologists being afraid of the possibility of inducing renal insufficiency in patients with a single kidney transplant. However, current knowledge of the ability of these agents to control blood pressure and urinary protein excretion, as well as post-transplant erythrocytosis, effectively in kidney transplant recipients suggests that it is now time to apply renin-angiotensin system blockers to the field of renal transplantation.