Renin-angiotensin System In Patients Research Articles

Inhibition of the renin-angiotensin system in patients with upper gastrointestinal adenocarcinoma.

Inhibition of the renin-angiotensin system in patients with upper gastrointestinal adenocarcinoma.

Renin-Angiotensin and Endothelin Systems in Patients Post-Takotsubo Cardiomyopathy.

Background We investigate if renin-angiotensin and endothelin-1 response pathways follow the same pattern of recovery as left ventricular ejection fraction in patients with takotsubo cardiomyopathy. Methods and Results Ninety patients with takotsubo cardiomyopathy (n=30 in each of "acute," "convalescent" [3-5 months] and "recovered" [>1 year] groups) who were on minimal or no medication and were free of any significant cardiac/metabolic comorbidities, and 30 controls were studied. Serum concentrations of renin, angiotensin-converting enzyme, angiotensin II, big endothelin-1, endothelin-1 were measured using commercially available ELISA, and B-type natriuretic peptide was measured using an immunoassay. Mean left ventricular ejection fraction was <40% during the acute phase in all groups, but recovered to 63% in convalescent and 64% in the recovered groups, respectively. Serum renin concentrations remain persistently elevated after a episode of takotsubo cardiomyopathy (P=0.03 versus controls). Angiotensin converting enzyme levels are significantly depressed during the acute phase compared with convalescent (P=0.004), recovered takotsubo cardiomyopathy (P=0.02) or controls (P=0.03). Angiotensin II is increased in patients with takotsubo cardiomyopathy (P<0.001 versus controls) remaining persistently elevated in the chronically recovered group alone (P=0.03 versus controls). Big endothelin-1 levels are unchanged, but endothelin-1 is significantly lower after takotsubo cardiomyopathy compared with controls (P=0.03). Conclusions Despite "normalization" of the left ventricular ejection fraction, there is long-term maladaptive activation of renin-angiotensin system in patients with takotsubo cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02897739, NCT02989454.

Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis: a randomized clinical trial

BackgroundAcidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis.MethodsPatients with CKD stage G4 and plasma bicarbonate 15–24 mmol/l were randomized to receive sodium bicarbonate (3 × 1000 mg/day, ~ 0.5 mEq/kg), sodium chloride (2 × 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed.ResultsForty-five patients were included (62 ± 15 years, eGFR 21 ± 5 ml/min/1.73m2, plasma bicarbonate 21.7 ± 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P < 0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or α1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and α1-microglobulin (all P < 0.05).ConclusionsDespite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity.Graphic abstract

The role of renin-angiotensin system in patients with left ventricular assist devices.

End-stage heart failure is a condition in which the up-regulation of the systemic and local renin-angiotensin-aldosterone system (RAAS) leads to end-organ damage and is largely irreversible despite optimal medication. Left ventricular assist devices (LVADs) can downregulate RAAS activation by unloading the left ventricle and increasing the cardiac output translating into a better end-organ perfusion improving survival. However, the absence of pulsatility brought about by continuous-flow devices may variably trigger RAAS activation depending on left ventricular (LV) intrinsic contractility, the design and speed of the pump device. Moreover, the concept of myocardial recovery is being tested in clinical trials and in this setting LVAD support combined with intense RAAS inhibition can promote recovery and ensure maintenance of LV function after explantation. Blood pressure control on LVAD recipients is key to avoiding complications as gastrointestinal bleeding, pump thrombosis and stroke. Furthermore, emerging data highlight the role of RAAS antagonists as prevention of arteriovenous malformations that lead to gastrointestinal bleeds. Future studies should focus on the role of angiotensin receptor inhibitors in preventing myocardial fibrosis in patients with LVADs and examine in greater details the target blood pressure for these patients.

Single versus dual blockade of the renin-angiotensin system in patients with IgA nephropathy

BackgroundInhibitors of the renin-angiotensin system (RAS) are cornerstones of supportive therapy in patients with IgA nephropathy (IgAN). We analyzed the effects of single versus dual RAS blockaQueryde during our randomized STOP-IgAN trial.MethodsSTOP-IgAN participants with available successive information on their RAS treatment regimen and renal outcomes during the randomized 3-year trial phase were stratified post hoc into two groups, i.e. patients under continuous single or dual RAS blocker therapy over the entire 3 years of the trial phase. Primary and secondary STOP-IgAN trial endpoints, i.e. frequencies of full clinical remission, eGFR-loss ≥ 15 and ≥ 30 ml/min/1.73 m2 and ESRD onset, were analyzed by logistic regression and linear mixed effects models.ResultsAmong the 112 patients included in the present analysis, 82 (73%) were maintained on single and 30 (27%) on dual RAS inhibitor therapy throughout the trial. Neither RAS blocker strategy significantly affected full clinical remission, eGFR-loss rates, onset of ESRD. Proteinuria moderately increased in patients under dual RAS blockade by 0.1 g/g creatinine during the 3-year trial phase. This was particularly evident in patients without additional immunosuppression during the randomized trial phase, where proteinuria increased by 0.2 g/g creatinine in the dual RAS blockade group. In contrast, proteinuria decreased in patients under single RAS blocker therapy by 0.3 g/g creatinine. The course of eGFR remained stable and did not differ between the RAS treatment strategies.ConclusionIn the STOP-IgAN cohort, neither RAS blocker regimen altered renal outcomes. Patients on dual RAS blockade even exhibited higher proteinuria over the 3-year trial phase.

Aldosterone and renin in cardiac patients referred for catheterization.

Little is known regarding alterations of the renin-angiotensin system in patients referred for cardiac catheterization. Here, we measured plasma levels of active renin and aldosterone in patients referred for cardiac catheterization in order to determine the prevalence of elevated renin, aldosterone, and the aldosterone-renin ratio.A chemiluminescence assay was used to measure plasma aldosterone concentration (PAC) and active renin levels in 833 consecutive patients, after an overnight fasting and without any medication for least 12 hours. We evaluated associations of the hormonal elevations in relation to hypertension, atrial fibrillation (AF), hypertensive cardiomyopathy, coronary artery disease (CAD), valvular disease, impaired left ventricular ejection fraction (LVEF < 35%), and pulmonary hypertension (arterial pulmonary mean pressure >25 mm Hg).Hyperaldosteronism occurred in around one-third of all examined patients, without significant differences between patients with or without the named cardiac diseases. In a comparison between patients with or without any given cardiac disease condition, renin was significantly elevated in patients with either hypertension (36.4% vs 15.9%), CAD (33.9% vs 22.1%), or impaired LVEF (47.3% vs 24.8%). The angiotensin-renin ratio was elevated in AF patients and in patients with hypertensive cardiomyopathy. Patients with AF and coexisting hypertension had elevated renin more frequently than AF patients without coexisting hypertension (35.3% vs 16.5%; P = .005). Patients with persistent/permanent AF more frequently had elevated renin than patients with paroxysmal AF (34.1% vs 15.8%; P = .007).This prospective study of consecutive cardiac disease patients referred for cardiac catheterization has revealed distinct cardiac disease condition-associated differences in the frequencies of elevations in plasma renin, PAC, and the aldosterone-renin ratio.

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA.

Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long-term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB.

The activity of renin-angiotensin system in patients with arterial hypertension in population of the Gornaia Shoria

The study was carried out to investigate characteristics of pathophysiological variants of arterial hypertension depending on activity of plasma renin in indigenous (Shors) and non-indigenous population of the Gornaia Shoria.The clinical epidemiological study was carried out concerning indigenous population of hard-to-reach regions of the Gornaia Shoria. The continuous sampling technique was applied on the basis of nominal lists to select 837 residents of the mentioned villages (513 personf of indigenous population (Shors) and 324 of non-indigenous population). The particular sampling consisted of adult population, including individuals of 18 years and older. The activity of plasma renin was evaluated using test-systems of BRG (Germany). All examined patients were separated in two groups. The first group included patients with arterial hypertension with concentration of plasma renin &gt; 47,85 picograms per ml (development of disease is related to excessive release of renin and activation of renin-angiotensin system). The second group included patients wit arterial hypertension with content of plasma renin &lt; 47,85 picograms per ml (arterial hypertension is related to suppression of release of renin and retention of sodium in organism). The renin - dependent arterial hypertension more was often found among representatives of non-indigenous nationality (89,8 % against 65,5%) and the volume-dependent arterial hypertension - among representatives of indigenous nationality (34,4 % against 10,1%). In the indigenous ethnic group of Shors the renin - dependent arterial hypertension was associated with younger age and expressed structural functional alterations of heart in the form of increased index of myocardium mass of left ventricle. The volume-dependent arterial hypertension was associated with average age and increased indicator of thick- Clinical medicine ness of complex of intima-media. In non-indigenous ethnic group the renin - dependent arterial hypertension was associated with increased level of index of waist/thigh. The volume-dependent arterial hypertension was associated with expressed structural functional alterations of heart in the form of increased index of myocardium mass of left ventricle.

Role of the Pharmacoeconomic Aspects in the Clinical Management of Hypertension.

Hypertension constitutes a significant disease burden to the society, both in terms of the health-related repercussions as well as financial costs incurred due to morbidity and the cumulative cost of drug therapy. In the real world, it would be useful to have the opportunity to consider the appropriate use of antihypertensive drugs to inform and guide clinical practice. To evaluate the adherence of drugs prescriptions in clinical practice according to predefined standards of care, a series of indicators measurable in relation to specific conditions have been developed. This work presents four indicators: the first related to the use of drugs acting on the renin-angiotensin system in patients at high cardiovascular risk; the second related to the use of angiotensin II antagonists with expired patent; the third related the occasional prescription of antihypertensive drugs; and the fourth on the adherence to treatment with antihypertensive drugs. The four indicators were measured in the OsMed database.

Addition of hydrochlorothiazide to angiotensin receptor blocker therapy can achieve a lower sodium balance with no acceleration of intrarenal renin angiotensin system in patients with chronic kidney disease.

Objective:Angiotensin receptor blockers (ARBs) produce a lower sodium (Na) balance, and the natriuretic effect is enhanced under Na deprivation, despite falls in blood pressure (BP) and glomerular filtration rate (GFR).Methods:The effect of additional hydrochlorothiazide (HCTZ; 12.5 mg/day) to ARB treatment (valsartan; 80 mg/day) on glomerulotubular Na balance was evaluated in 23 patients with chronic kidney disease.Results:Add-on HCTZ decreased GFR, tubular Na load, and tubular Na reabsorption (tNa), although 24-hour urinary Na excretion (UNaV) remained constant. Daily urinary angiotensinogen excretion (UAGTV, 152±10→82±17 μg/g Cre) reduced (p=0.02). Changes in tubular Na load (r2=0.26) and tNa (r2=0.25) correlated with baseline 24-hour UAGTV. Changes in filtered Na load correlated with changes in nighttime systolic BP (r2=0.17), but not with changes in daytime systolic BP. The change in the tNa to filtered Na load ratio was influenced by the change in daytime UNaV (β=−0.67, F=16.8), rather than the change in nighttime UNaV.Conclusions:Lower Na balance was produced by add-on HCTZ to ARB treatment without an increase of intra-renal renin-angiotensin system activity, leading to restoration of nocturnal hypertension. A further study is needed to demonstrate that the reduction of UAGTV by additional diuretics to ARBs prevents the progression of nephropathy or cardiovascular events.

Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced HCC patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group.

Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (−0.30, p=0.0008) in the responder group (−0.58, p=0.003) than in those with progressive disease (−0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatment.

Endothelial dysfunction, activity of renin-angiotensin system in patients with postinfarction cardiosclerosis after cardiac surgical revascularization

Objectives: Intimal hyperplasia is a vascular remodeling process. It is a clinical problem that forms in the vascular wall as a result of smooth muscle cell migration, proliferation, and extracellular matrix accumulation. RAAS inhibition using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers has become a standard pharmatherapeutic procedure, however it is not have enave ability under post-ischemic-reperfusion state, portal and pulmonary hypertension to cessation vascular remodeling process. The aim of this work was to search new rational medical technology of optimization of postoperative treatment of patients with cardiosclerosis, directed on simultaneous correction of the endothelial dysfunction.

Anesthesia Literature Review

Anesthesia Literature Review

Renin-Angiotensin-Aldosterone System Antagonists and the Prevention of Type 2 Diabetes Mellitus

ACE inhibitors have established their role in the management of hypertension as well as in the primary and secondary prevention of cardiovascular events. Furthermore, they have proven their role in delaying the worsening of renal function in patients with chronic renal disease. Over the last few years their use to prevent the new onset of diabetes has come to the forefront. Post-hoc analyses of large multi-center clinical trials such as the Captopril Prevention Project and the Heart Outcomes Prevention Evaluation have suggested that their use may delay or prevent the onset of diabetes. However many of these results are based on secondary analyses and few prospective clinical trials exist. In the two prospective trial so far conducted regarding the use of ACEi and ARB as a means to diabetes prevention the effects of these drugs compared to lifestyle modifications have been minimal and do not yet warrant their use to this effect. While there is strong evidence for modulation the Renin-Angiotensin System in patients with hypertension, coronary heart disease and renal dysfunction the evidence for preventing diabetes remains scarce and will need to be investigated further.

Careful re-evaluation of the impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease

Careful re-evaluation of the impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease

The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease

The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease

Blockade of Endothelial-Mesenchymal Transition by a Smad3 Inhibitor Delays the Early Development of Streptozotocin-Induced Diabetic Nephropathy

OBJECTIVEA multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated that endothelial-mesenchymal-transition (EndoMT) contributes to the early development of renal interstitial fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)-induced diabetes. In the present study, we hypothesized that blocking EndoMT reduces the early development of diabetic nephropathy.RESEARCH DESIGN AND METHODSEndoMT was induced in a mouse pancreatic microvascular endothelial cell line (MMEC) in the presence of advanced glycation end products (AGEs) and in the endothelial lineage–traceble mouse line Tie2-Cre;Loxp-EGFP by administration of AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3 was detected by immunoprecipitation/Western blotting and confocal microscopy. Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3 (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice.RESULTSConfocal microscopy and real-time PCR demonstrated that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice. Immunoprecipitation/Western blotting showed that Smad3 was activated by AGEs but was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT, reduced renal fibrosis, and retarded progression of nephropathy.CONCLUSIONSEndoMT is a novel pathway leading to early development of diabetic nephropathy. Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression of diabetic nephropathy and other diabetes complications.

Effect of Pulsatile and Non-pulsatile Left Ventricular Assist Devices on the Renin-Angiotensin System in Patients with End-Stage Heart Failure

Left ventricular assist devices have been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement of their heart failure after LVAD implantation, we studied the physiological effect of pulsatile and non-pulsatile devices on the neurohormonal axis and exercise capacity. We prospectively included 20 patients (17 men, 3 women) undergoing LVAD implantation between November 2001 and January 2004. Ten patients (1 woman and 9 men) were treated with the non-pulsatile INCOR-LVAD (Berlin Heart(c)) and ten patients received the pulsatile EXCOR LVAD (Berlin Heart(c)). Blood samples for plasma renin activity (PRA) were taken once a week over a period of ten weeks. All blood samples were collected in the morning before mobilization. Blood pressure, body weight, fluid intake and urine production were measured once a day. All patients received standard hospital diet with no limitation in fluid intake. Body weight remained constant in both groups throughout the ten weeks' examination, and fluid intake and urine production were balanced in all patients. Although there was no significant difference in mean blood pressure (INCOR: 70 +/- 10 mmHg; EXCOR: 73 +/- 10 mmHg), plasma renin activity was substantially elevated in patients with non-pulsatile left ventricular support (INCOR: 94.68 +/- 33.97 microU/ml; EXCOR: 17.06 +/- 15.94 microU/ml; P < 0.05). Furthermore plasma aldosterone levels were significantly higher in patients supported by non-pulsatile INCOR LVAD (INCOR: 73.4 +/- 9.6 microg/ml; EXCOR: 20.6 +/- 4.6 microg/ml; P < 0.05). Our data suggest that pulsatile as well as non-pulsatile left ventricular assist devices are equally able to treat chronic heart failure. However pulsatile devices seem to have a greater impact on reversing the changes in plasma renin activity and might thus offer a greater advantage when recovery of left ventricular function is expected.

Angiotensin II receptor type 1 is upregulated in atrial tissue of patients with rheumatic valvular disease with atrial fibrillation

The purpose of this study was to examine the changes in expression of angiotensin II receptor type 1/2 in left or right atrial tissue from patients with rheumatic valvular disease with or without atrial fibrillation. Atrial tissue samples were obtained from 39 patients with rheumatic mitral valve disease during cardiac surgery. Among these patients, there were 25 with atrial fibrillation and 14 with sinus rhythm. The level of angiotensin II receptor type 1 or type 2 mRNA transcription was measured by means of a semiquantitative reverse transcription-polymerase chain reaction technique. Expression of angiotensin II receptor type 1 or type 2 protein was detected by means of immunohistochemistry assay and Western blot analysis. The inner diameter of the left atrium was clearly enlarged in the atrial fibrillation group in comparison with that seen in the sinus rhythm group. The expression levels of both angiotensin II receptor type 1 mRNA and protein in the left atrial tissue were significantly increased in the patients with atrial fibrillation compared with those seen in patients with sinus rhythm (P < .05). Interestingly, the comparison of angiotensin II receptor type 2 expression levels in the left atrial tissue between these 2 groups is not statistically significant. In addition, the results of angiotensin II receptor type 1 or 2 expression in the right atrial tissue did not show any obvious change in the patients with atrial fibrillation versus those with sinus rhythm. Expression of angiotensin II receptor type 1 but not type 2 is highly upregulated only in the left atrial tissue of patients with rheumatic valvular disease with atrial fibrillation. This suggests that there is a possible pathophysiologic role of the renin-angiotensin system in patients with atrial fibrillation and that a series of effects mediated by the activation of angiotensin II receptor type 1 in the left atrial tissue might be one of the molecular mechanisms involved in the process of atrial remodeling in atrial fibrillation.

“Effective” Plasma Renin Activity: A Derived Measure for Assessing Residual Plasma Renin Activity in Patients Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers

To the Editor: The plasma renin activity (PRA) test quantifies the circulating activity of the renin-angiotensin system by measuring the rate at which renin forms angiotensin I (Ang I) in plasma. The PRA test overestimates the true activity of the circulating renin-angiotensin system in patients taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) because these drugs block the system at sites distal to the enzymatic release of Ang I by plasma renin.1,2 When patients are taking these drugs, a simple calculation can be used to determine …