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Lionel Lattenist, Sebastian M Lechner, Smail Messaoudi, Alan Le Mercier, Soumaya El Moghrabi, Sonia Prince, Norma A Bobadilla, Peter Kolkhof, Frédéric Jaisser, Jonatan Barrera-Chimal
Acute kidney injury induced by ischemia/reperfusion (IR) is a frequent complication in hospitalized patients. Mineralocorticoid receptor antagonism has shown to be helpful against renal IR consequences; however, the potential benefit of novel nonsteroidal mineralocorticoid receptor antagonists such as finerenone has to be further explored. In this study, we evaluated the efficacy of finerenone to prevent the acute and chronic consequences of ischemic acute kidney injury. For the acute study (24 hours), 18 rats were divided into sham, bilateral renal ischemia of 25 minutes, and rats that received 3 doses of finerenone at 48, 24, and 1 hour before the ischemia...
March 20, 2017: Hypertension
Charles Faselis, Chrysoula Boutari, Michael Doumas, Konstantinos Imprialos, Konstantinos Stavropoulos, Peter Kokkinos
BACKGOUND: Current drug therapy for the management of arterial hypertension and heart failure has provided substantial benefits but has also some limitations. LCZ696, a dual inhibitor of angiotensin receptor blockers and neprilysin, and finerenone, a non-steroidal mineralocorticoid receptor antagonist, are two recently developed novel agents for the management of these conditions. METHODS: This review aims to present the pathophysiological basis for the use of these two novel drugs, critically discuss available clinical data, and provide future perspectives...
February 6, 2017: Current Pharmaceutical Design
Richard E Gilbert
No abstract text is available yet for this article.
April 2017: Journal of Diabetes and its Complications
Jonatan Barrera-Chimal, Gwennan André-Grégoire, Aurelie Nguyen Dinh Cat, Sebastian M Lechner, Jérôme Cau, Sonia Prince, Peter Kolkhof, Gervaise Loirand, Vincent Sauzeau, Thierry Hauet, Frédéric Jaisser
AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury...
April 2017: Journal of the American Society of Nephrology: JASN
Shigehiro Katayama, Daishiro Yamada, Mikihiro Nakayama, Takashi Yamada, Masafumi Myoishi, Masaharu Kato, Christina Nowack, Peter Kolkhof, Yoshimitsu Yamasaki
AIMS: Finerenone (BAY 94-8862) is a novel non-steroidal mineralocorticoid receptor antagonist. The aim of this study was to compare the efficacy and safety of seven once-daily oral doses of finerenone (1.25-20mg) and placebo in 96 patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) receiving a RAS blocker. METHODS: ARTS-DN Japan was a multicenter, randomized, double-blind, placebo-controlled, phase 2b study. RESULTS: Analysis of the urinary albumin-to-creatinine ratio (UACR) at day 90 relative to baseline indicated a nominally significant effect of finerenone...
April 2017: Journal of Diabetes and its Complications
Peter Kolkhof, Frederic Jaisser, So-Young Kim, Gerasimos Filippatos, Christina Nowack, Bertram Pitt
Characterization of mice with cell-specific deletion or overexpression of the mineralocorticoid receptor (MR) shed a new light on its role in health and disease. Pathophysiological MR activation contributes to a plethora of deleterious molecular mechanisms in the development of cardiorenal diseases like chronic kidney disease (CKD) and heart failure (HF). Accordingly, the available steroidal MR antagonists (MRAs) spironolactone (first generation MRA) and eplerenone (second generation MRA) have been shown to be effective in reducing cardiovascular (CV) mortality and morbidity in patients with chronic HF and a reduced left ventricular ejection fraction (HFrEF)...
November 10, 2016: Handbook of Experimental Pharmacology
L M Ruilope, C Nowack, G L Bakris
No abstract text is available yet for this article.
July 2016: Journal of the American Society of Hypertension: JASH
Pingping Yang, Tianlun Huang, Gaosi Xu
No abstract text is available yet for this article.
September 2016: Metabolism: Clinical and Experimental
Roland Heinig, Nina Kimmeskamp-Kirschbaum, Atef Halabi, Silvia Lentini
Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. This observational trial compared the pharmacokinetics of a single oral dose of finerenone 10 mg (immediate-release tablet) in adults with mild (creatinine clearance [CLCR ] 50-80 mL/min; n = 8), moderate (CLCR 30 to < 50 mL/min; n = 8), or severe (CLCR < 30 mL/min; n  =  9) renal impairment with those in adults with normal renal function (CLCR > 80 mL/min; n  = 8) over 96 hours postdose...
November 2016: Clinical Pharmacology in Drug Development
Claire McCune, Peter McKavanagh, Ian B A Menown
INTRODUCTION: Multiple significant, potentially practice changing clinical trials in cardiology have been conducted and subsequently presented throughout the past year. METHODS: In this paper, the authors have reviewed and contextualized significant cardiovascular clinical trials presented at major international conferences of 2015 including American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, American Diabetes Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Rhythm Congress, and the American Heart Association Scientific Sessions...
December 2016: Cardiology and Therapy
Karina Huynh
No abstract text is available yet for this article.
July 2016: Nature Reviews. Cardiology
Duygu Batu Demir, Mark E Cooper
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of recent preclinical and clinical studies, which demonstrate new insights for the treatment of diabetic kidney disease (DKD) and to outline future directions with respect to novel therapies. RECENT FINDINGS: Positive findings with respect to new glucose-lowering agents such as sodium-dependent glucose transporter 2 inhibitors may lead to a change in the way we treat diabetic individuals with or at risk of DKD...
July 2016: Current Opinion in Nephrology and Hypertension
Matthias Naegele, Adrian F Hernandez, Frank Ruschitzka
No abstract text is available yet for this article.
July 14, 2016: European Heart Journal
Gerasimos Filippatos, Stefan D Anker, Michael Böhm, Mihai Gheorghiade, Lars Køber, Henry Krum, Aldo P Maggioni, Piotr Ponikowski, Adriaan A Voors, Faiez Zannad, So-Young Kim, Christina Nowack, Giovanni Palombo, Peter Kolkhof, Nina Kimmeskamp-Kirschbaum, Alexander Pieper, Bertram Pitt
AIMS: To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. METHODS AND RESULTS: Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study ( NCT01807221). Of 1286 screened patients, 1066 were randomized...
July 14, 2016: European Heart Journal
Hermann Haller, Anna Bertram, Klaus Stahl, Jan Menne
Aldosterone binds to the mineralocorticoid receptor and has an important regulatory role in body fluid and electrolyte balance. It also influences a variety of different cell functions such as oxidative stress, inflammation and organ fibrosis. The important role of the tissue-specific mineralocorticoid receptors in cardiovascular and renal injury has been shown in knockout animals and in clinical studies Mineralocorticoid receptor antagonists seem to exert their beneficial effects via anti-oxidative, anti-inflammatory and anti-fibrotic effects...
April 2016: Current Hypertension Reports
Hao A Tran, Felice Lin, Barry H Greenberg
INTRODUCTION: The prevalence of heart failure (HF) has increased globally in recent decades. Advances in our understanding of underlying pathophysiologic mechanisms have given rise to new therapies for treating the growing HF population. Nonetheless, morbidity and mortality associated with HF and its financial implications are daunting. Thus, novel therapies that can improve the natural history of HF patients are urgently needed. AREAS COVERED: This article reviews new investigational drugs being developed for the treatment of both acute decompensated heart failure (ADHF) and chronic heart failure with reduced ejection fraction (HFrEF)...
July 2016: Expert Opinion on Investigational Drugs
Naoki Sato, Masayoshi Ajioka, Takahisa Yamada, Masaharu Kato, Masafumi Myoishi, Takashi Yamada, So-Young Kim, Christina Nowack, Peter Kolkhof, Tsuyoshi Shiga
BACKGROUND: Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, was evaluated in Japanese patients with heart failure (HF) with reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. METHODS AND RESULTS: ARTS-HF Japan was a randomized, double-blind, phase 2b study. Patients (n=72) received oral, once-daily (o.d.) finerenone (2.5, 5, 7.5, 10 or 15 mg, up-titrated to 5, 10, 15, 20, or 20 mg, respectively, on day 30) or eplerenone (25 mg every other day, increased to 25 mg o...
April 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Alexandre Gueret, Najah Harouki, Julie Favre, Guillaume Galmiche, Lionel Nicol, Jean-Paul Henry, Marie Besnier, Christian Thuillez, Vincent Richard, Peter Kolkhof, Paul Mulder, Frédéric Jaisser, Antoine Ouvrard-Pascaud
Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In this study, the role of MR expressed in vascular smooth muscle cells (VSMCs) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis...
April 2016: Hypertension
Jana Grune, Verena Benz, Sarah Brix, Janek Salatzki, Annelie Blumrich, Beata Höft, Robert Klopfleisch, Anna Foryst-Ludwig, Peter Kolkhof, Ulrich Kintscher
Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. Therapy with steroidal MR antagonists such as spironolactone or eplerenone (EPL) is often limited because of side effects. Recently, a new highly selective and potent, nonsteroidal MR antagonist, finerenone (FIN), has been developed. To investigate the effects of FIN on pressure-induced cardiac hypertrophy, the transverse aortic constriction (TAC) model was used in C57BL/6 mice treated with FIN (10 mg·kg·d), EPL (200 mg·kg·d) or vehicle (VEH)...
May 2016: Journal of Cardiovascular Pharmacology
Peter Bramlage, Stephanie L Swift, Martin Thoenes, Joan Minguet, Carmen Ferrero, Roland E Schmieder
Pharmaceutical antagonism of the mineralocorticoid receptor (MR) can protect against organ damage caused by elevated aldosterone levels in patients experiencing heart failure (HF), chronic kidney disease (CKD), primary aldosteronism, and hypertension. While traditional steroid-based MR antagonists effectively reduce mortality rates and extend patient survival, their broad application has been limited by significant side effects, most notably hyperkalaemia. Recently, finerenone (BAY 94-8862) has emerged as a next-generation non-steroidal dihydropyridine-based MR antagonist designed to minimize off-target effects while maintaining potent efficacy...
January 2016: European Journal of Heart Failure
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