aliskiren

AIM: To create and validate a prediction model to identify patients with type 2 diabetes (T2D) at high risk of new-onset heart failure (HF), including those treated with a sodium-glucose cotransporter-2 (SGLT2) inhibitor. METHODS: A prediction model was developed from the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE), a trial in T2D patients with albuminuria or cardiovascular disease. We included 5081 patients with baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) measurement and no history of HF...

BACKGROUND/AIM: The renin-angiotensin system (RAS) regulates blood pressure. The RAS is also related to cell growth, and its activation has been reported in various cancer cells. Therefore, we investigated the effects of RAS inhibitors on the in vitro growth of leukemia cell lines. MATERIALS AND METHODS: THP-1, MV4-11, and TMD7 cells derived from acute myeloid leukemia, K-562 cells from chronic myeloid leukemia, and Jurkat and KOPT-K1 cells from T-lymphoblastic leukemia (T-ALL) with NOTCH1 mutations were used...

We aimed to determine effects of aliskiren, a direct renin inhibitor, loaded onto polymeric nanoparticles on the (pro)renin receptor ( Atp6ap2 ), angiotensin II type 1 receptor ( Agtr1 ), and angiotensin-converting enzyme ( ACE ) gene expression in the heart of spontaneously hypertensive rats (SHR). Twelve-week-old male SHRs were divided into an untreated group and groups treated with powdered aliskiren or aliskiren-loaded nanoparticles (25 mg/kg/day). After three weeks, the accumulation of aliskiren, distribution of polymeric nanoparticles, gene expression of Atp6ap2 and Agtr1 receptors and ACE , and protein expression of NADPH oxidase along with the conjugated diene (CD) concentration were analyzed...

A middle-aged woman presented with hypertensive emergency after corticosteroid treatment for Sjögren syndrome-associated multiple mononeuropathy with suspected systemic sclerosis. Hypertensive heart failure with hyperreninemia improved with antihypertensives, including aliskiren; however, she became hemodialysis-dependent. Clinical findings and biopsy-proven thrombotic microangiopathy indicated conditions resembling scleroderma renal crisis (SRC). Severe hypertension and heart failure with hyperreninemia occurred after stopping aliskiren for hypotension due to diverticular bleeding, which improved after the reintroduction of aliskiren...

The rise of Plasmodium falciparum resistance to Artemisinin-based combination therapies (ACTs) is a significant concern in the fight against malaria. This situation calls for the search for novel anti-malarial candidates. 1-deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) is a potential target involved in various cellular processes in P. falciparum (Pf). We screened ~0.69 billion novel compounds from the ZINC20 library and repurposed ~1400 FDA drugs using computational drug discovery methods against PfIspC...

Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested that renin may also cleave complement component C3 to activate complement or contribute to its dysregulation. Typically, C3 is cleaved by C3 convertase, a serine protease that uses the hydroxyl group of a serine residue as a nucleophile. Here, we provide seven lines of evidence to show that renin does not cleave C3. First, there is no association between renin plasma levels and C3 levels in patients with C3 Glomerulopathies (C3G) and atypical Hemolytic Uremic Syndrome (aHUS), implying that serum C3 consumption is not increased in the presence of high renin...

UNLABELLED: The temporal response of changes in renal sodium reabsorption during increased renal sympathetic nerve activity has not been investigated. Central hypovolemia by application of lower-body negative-pressure (LBNP) elicits baroreceptor mediated sympathetic reflexes to maintain arterial blood pressure. We hypothesized, that during 90 min LBNP, the renal sodium retention would increase rapidly, remain increased during intervention, and return to baseline immediately after end of intervention...

BACKGROUND: Renin-dependent hypertension with tubulointerstitial injury remains a problem with high prevalence in the clinic. However, whether and how renin participates in tubulointerstitial injury remains incompletely understood. New evidence suggests that renin cleaves C3 into C3a and C3b. In the present study, we aimed to explore the role of renin-mediated C3a/C3a receptor (C3aR) signaling in renin-dependent hypertension-induced kidney injury and illustrate the detailed mechanisms...

SIGNIFICANCE STATEMENT: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR but does not weigh the relative clinical importance of the end point components. By contrast, a hierarchical composite end point (HCE) accounts for the clinical importance of the end point components. The authors developed and validated a kidney HCE that combines clinical kidney outcomes with longitudinal GFR changes (GFR slope). They demonstrate that in seven major placebo-controlled kidney outcome trials with different medications, treatment effect estimates on the HCE were consistently in similar directions and of similar magnitudes compared with treatment effects on the established kidney end point...

INTRODUCTION: Renin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of direct renin inhibitor as monotherapy has not been assessed. Here we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity. METHODS: In this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28...

BACKGROUND: The rehospitalization rate in hypertensive emergency is high, indicating the necessity for optimizing its long-term management. The role of the renin-angiotensin system (RAS) blockade in this disorder remains uncertain. METHODS: We conducted a retrospective analysis involving 20 admitted patients who received aliskiren, a direct renin inhibitor (DRI), for the management of hypertensive emergency associated with elevated plasma renin activity (PRA). We analyzed the changes in blood pressure (BP), kidney function, and RAS activity in the subacute and chronic phases...

The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer's dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels...

BACKGROUND: Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences...

Flavonoids have various pharmacological activities, such as antihypertensive, anticancer, and and antidiabetic effects. Several studies have shown that luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin have antihypertensive effects, but the mechanism of action has yet to be discovered with certainty. This study aims to identify flavonoids from luteolin, quercetin, kaempferol, myricetin, naringenin, hesperetin, and epicatechin as renin inhibitors through in silico study; seven flavonoid compounds were docked with 2V0Z with renin inhibitor (Aliskiren) in humans (Homo sapiens 6 LU7) using AutoDock v4...

Candidosis is one of the most frequent opportunistic infections and exhibits variable clinical presentations, including oral localized forms. Drugs affecting the renin-angiotensin system targets inhibit secreted aspartic proteases from Candida albicans . The objective of the study was to evaluate whether losartan has antimicrobial action against C. albicans biofilms. Biofilms were treated with losartan or aliskiren (for comparison) for 24 h. Metabolic activity of viable cells and growth inhibition of C...

AIMS: Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. METHODS AND RESULTS: Using two clinical trials in HF - the Prospective comparison of ARNI (Angiotensin Receptor-Neprilysin Inhibitor) with ACEI (Angiotensin-Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM-HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE) - we identified the 10 most common comorbidities and examined 45 possible pairs...

[This corrects the article doi: 10.1590/1414-431X20198793].

Chronic kidney disease presents a health challenge that has a complex underlying pathophysiology, both acquired and inherited. The pharmacotherapeutic treatment options available today lower the progression of the disease and improve the quality of life but cannot completely cure it. This poses a challenge to the healthcare provider to choose, from the available options, the best way to manage the disease as per the presentation of the patient. As of now, the recommended first line of treatment to control the blood pressure in chronic kidney disease is the administration of renin-angiotensin-aldosterone system modulators...

Anticancer drug resistance is one of the biggest hurdles in the treatment of breast cancer. Drug repurposing is a viable option fordeveloping novel medical treatment strategies since this method is more cost-efficient and rapid. Antihypertensive medicines have recently been found to have pharmacological features that could be used to treat cancer, making them effective candidates for therapeutic repurposing. The goal of our research is to find a potent antihypertensive drug that can be repurposed as adjuvant therapy for breast cancer...

INTRODUCTION: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown. METHODS: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality...