Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Hypertension Reports
Erschienen in: Current Hypertension Reports 5/2016

01.04.2016 | Therapeutic Trials (M Weir, Section Editor)

Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?

verfasst von: Hermann Haller, Anna Bertram, Klaus Stahl, Jan Menne

Erschienen in: Current Hypertension Reports | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

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. Spironolactone and eplerenone were the first steroidal mineralocorticoid receptor antagonist. The established steroidal mineralocorticoid receptor antagonists show important therapeutic effects but are hampered by a variety of side effects, most importantly clinically significant hyperkaliemia. Selective non-steroidal mineralocorticoid receptor antagonists have been recently developed and demonstrate effectiveness in early clinical trials. Finereroneholds promise for the future application of this new mineralocorticoid receptor antagonist class in patients with chronic kidney disease since it has shown a significant reduction in UACR combined with a safety profile similar to that in the placebo group. However, further long-term studies investigating relevant clinical end points like reduction in cardiovascular or renal event rate are warranted.
Literatur
1.••
Fuller PJ, Young MJ. Mechanisms of mineralocorticoid action. Hypertension. 2005;46:1227–35. Comprehensive review on the molecular mechanisms of mineralocorticoids.CrossRefPubMed
2.
Fuller PJ, Yao Y, Yang J, Young MJ. Mechanisms of ligand specificity of the mineralocorticoid receptor. J Endocrinol. 2012;213:15–24.CrossRefPubMed
3.
Lombes M, Alfaidy N, Eugene E, Lessana A, Farman N, Bonvalet J-P. Prerequisite for cardiac aldosterone action: mineralocorticoid receptor and 11β-hydroxysteroid dehydrogenase in the human heart. Circulation. 1995;92(2):175–82.CrossRefPubMed
4.
Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L, Lombès M. The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology. Nucl Recept Signal. 2007;5, e012.PubMedPubMedCentral
5.••
Bader M. Tissue renin-angiotensin-aldosterone systems: Targets for pharmacological therapy. Annu Rev Pharmacol Toxicol. 2010;50:439–65. This review by an international expert on RASS system gives a comprehensive overview on established and future therapeutic targets. Provides insight into molecular studies of the RAAS system.CrossRefPubMed
6.
Taves MD, Gomez-Sanchez CE, Soma KK. Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am J Physiol Endocrinol Metab. 2011;301:E11–24.CrossRefPubMedPubMedCentral
7.
Johar S, Cave AC, Narayanapanicker A, Grieve DJ, Shah AM. Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase. FASEB J. 2006;20:1546–8.CrossRefPubMed
8.
Park YM, Lim BH, Touyz RM, Park JB. Expression of NAD(P)H oxidase subunits and their contribution to cardiovascular damage in aldosterone/salt-induced hypertensive rat. J Korean Med Sci. 2008;23(6):1039–45.CrossRefPubMedPubMedCentral
9.
Michea L, Villagrán A, Urzúa A, Kuntsmann S, Venegas P, Carrasco L, et al. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and prevents oxidative stress in uremic rats. Hypertension. 2008;52(2):295–300.CrossRefPubMed
10.
Mayyas F, Alzoubi KH, Van Wagoner DR. Impact of aldosterone antagonists on the substrate for atrial fibrillation: aldosterone promotes oxidative stress and atrial structural/electrical remodeling. Int J Cardiol. 2013;168:5135–42.CrossRefPubMedPubMedCentral
11.••
Karbach S, Wenzel P, Waisman A, Munzel T, Daiber A. eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation. Curr Pharm Des. 2014;20:3579–94. This review explains the intricate relationship between inflammation and oxidative stress and unravels the complicated mechanisms of oxidative stress in cardiovascular disease.CrossRefPubMed
12.••
Schiffrin EL. The immune system: role in hypertension. Can J Cardiol. 2013;29:543–8. Schiffrin gives an overview on the recent devlopments in this novel and intriguing research field in cardiovascular medicine.CrossRefPubMed
13.
Bene NC, Alcaide P, Wortis HH, Jaffe IZ. Mineralocorticoid receptors in immune cells: emerging role in cardiovascular disease. Steroids. 2014;91:38–45.CrossRefPubMed
14.
Kasal DA, Schiffrin EL. Angiotensin II, aldosterone, and anti-inflammatory lymphocytes: interplay and therapeutic opportunities. Int J Hypertens. 2012;2012:829786.PubMedPubMedCentral
15.
De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury. Arterioscler Thromb Vasc Biol. 2005;25:2106–13.CrossRefPubMed
16.
Rickard AJ, Morgan J, Chrissobolis S, Miller AA, Sobey CG, Young MJ. Endothelial cell mineralocorticoid receptors regulate DOC/salt-mediated cardiac remodeling and vascular reactivity, but not blood pressure. Hypertension. 2014;63:1033–40.CrossRefPubMed
17.
Liu Y, Hirooka K, Nishiyama A, Lei B, Nakamura T, Itano T, et al. Activation of the aldosterone/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia-reperfusion injury. Exp Eye Res. 2012;96:116–23.CrossRefPubMed
18.
Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S, Schütz G, et al. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest. 2010;120:3350–64.CrossRefPubMedPubMedCentral
19.
Marzolla V, Armani A, Feraco A, De Martino MU, Fabbri A, Rosano G, et al. Mineralocorticoid receptor in adipocytes and macrophages: a promising target to fight metabolic syndrome. Steroids. 2014;91:46–53.CrossRefPubMed
20.•
Herrada AA, Campino C, Amador CA, Michea LF, Fardella CE, Kalergis AM. Aldosterone as a modulator of immunity: implications in the organ damage. J Hypertens. 2011;29:1684–92. Review of the literature to explain how aldosterone affects the immune system and which implication ensue for cardiovascular disease.CrossRefPubMed
21.
Herrada AA, Contreras FJ, Marini NP, Amador CA, González PA, Cortés CM, et al. Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity. J Immunol. 2010;184:191–202.CrossRefPubMed
22.
Kasal DA, Barhoumi T, Li MW, Yamamoto N, Zdanovich E, Rehman A, et al. T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension. 2012;59:324–30.CrossRefPubMed
23.
Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P, Romero JR, et al. Mineralocorticoid receptor blockade reverses obesity-related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation. 2008;117:2253–61.CrossRefPubMedPubMedCentral
24.••
Anders HJ, Schaefer L. Beyond tissue injury-damage-associated molecular patterns, toll-like receptors, and inflammasomes also drive regeneration and fibrosis. J Am Soc Nephrol. 2014;25:1387–400. Important revew on the role of the innate immune system in renal and cardiovascular disease. Provides also insight into mechanisms of inflammasome and cardiovascular disease.CrossRefPubMedPubMedCentral
25.
Frantz S, Monaco C, Arslan F. Danger signals in cardiovascular disease. Mediat Inflamm. 2014;2014:395278.CrossRef
26.
Thomas W, Dooley R, Harvey BJ. Aldosterone as a renal growth factor. Steroids. 2010;75:550–4.CrossRefPubMed
27.
Dooley R, Harvey BJ, Thomas W. The regulation of cell growth and survival by aldosterone. Front Biosci (Landmark Ed). 2011;16:440–57.CrossRef
28.
Dooley R, Harvey BJ, Thomas W. Non-genomic actions of aldosterone: from receptors and signals to membrane targets. Mol Cell Endocrinol. 2012;350:223–34.CrossRefPubMed
29.
Iraqi W, Rossignol P, Angioi M, Fay R, Nuée J, Ketelslegers JM, et al. Extracellular cardiac matrix biomarkers in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) study. Circulation. 2009;119:2471–9.CrossRefPubMed
30.
Lacolley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation. 2002;106:2848–53.CrossRefPubMed
31.
Bauersachs J, Jaisser F, Toto R. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015;65:257–63.CrossRefPubMed
32.
Vazquez-Rangel A, Soto V, Escalona M, Toledo RG, Castillo EA, Polanco Flores NA, et al. Spironolactone to prevent peritoneal fibrosis in peritoneal dialysis patients: a randomized controlled trial. Am J Kidney Dis. 2014;63:1072–4.CrossRefPubMed
33.
Yelken B, Gorgulu N, Gursu M, Yazici H, Caliskan Y, Telci A, et al. Effects of spironolactone on residual renal function and peritoneal function in peritoneal dialysis patients. Adv Perit Dial. 2014;30:5–10.PubMed
34.
Zhang L, Hao JB, Ren LS, Ding JL, Hao LR. The aldosterone receptor antagonist spironolactone prevents peritoneal inflammation and fibrosis. Lab Invest. 2014;94:839–50.CrossRefPubMed
35.
Pizarro M, Solis N, Quintero P, Barrera F, Cabrera D, Rojas-de Santiago P, et al. Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis. Liver Int. 2015;35:2129–38.CrossRefPubMed
36.
Mitts TF, Bunda S, Wang Y, Hinek A. Aldosterone and mineralocorticoid receptor antagonists modulate elastin and collagen deposition in human skin. J Invest Dermatol. 2010;130:2396–406.CrossRefPubMed
37.
Marney AM, Brown NJ. Aldosterone and end-organ damage. Clin Sci (Lond). 2007;113:267–78.CrossRef
38.
Rautureau Y, Paradis P, Schiffrin EL. Cross-talk between aldosterone and angiotensin signaling in vascular smooth muscle cells. Steroids. 2011;76:834–9.PubMed
39.
Lemarié CA, Simeone SM, Nikonova A, Ebrahimian T, Deschênes ME, Coffman TM, et al. Aldosterone-induced activation of signaling pathways requires activity of angiotensin type 1a receptors. Circ Res. 2009;105:852–9.CrossRefPubMed
40.
Virdis A, Neves MF, Amiri F, Viel E, Touyz RM, Schiffrin EL. Spironolactone improves angiotensin-induced vascular changes and oxidative stress. Hypertension. 2002;40:504–10.CrossRefPubMed
41.
Kobayashi N, Hara K, Tojo A, Onozato ML, Honda T, Yoshida K, et al. Eplerenone shows renoprotective effect by reducing LOX-1-mediated adhesion molecule, PKCepsilon-MAPK-p90RSK, and Rho-kinase pathway. Hypertension. 2005;45:538–44.CrossRefPubMed
42.
Nagase M, Fujita T. Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease. Nat Rev Nephrol. 2013;9:86–98.CrossRefPubMed
43.
Bertocchio JP, Warnock DG, Jaisser F. Mineralocorticoid receptor activation and blockade: an emerging paradigm in chronic kidney disease. Kidney Int. 2011;79:1051–60.CrossRefPubMed
44.
Ritz E, Tomaschitz A. Aldosterone and the kidney: a rapidly moving frontier (an update). Nephrol Dial Transplant. 2014;29:2012–9.CrossRefPubMed
45.
Bobadilla NA, Gamba G. New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone. Am J Physiol Renal Physiol. 2007;293:F2–9.CrossRefPubMed
46.
Amador CA, Barrientos V, Peña J, Herrada AA, González M, Valdés S, et al. Spironolactone decreases DOCA-salt-induced organ damage by blocking the activation of T helper 17 and the downregulation of regulatory T lymphocytes. Hypertension. 2014;63:797–803.CrossRefPubMed
47.
Waanders F, Rienstra H, Boer MW, Zandvoort A, Rozing J, Navis G, et al. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol. 2009;296:F1072–9.CrossRefPubMed
48.
Juncos LA, Juncos LI (2015) Mineralocorticoid receptor antagonism in AKI: a new hope? J Am Soc Nephrol
49.
Barrera-Chimal J, Pérez-Villalva R, Rodríguez-Romo R, Reyna J, Uribe N, Gamba G, et al. Spironolactone prevents chronic kidney disease caused by ischemic acute kidney injury. Kidney Int. 2013;83:93–103.CrossRefPubMed
50.
Sánchez-Pozos K, Barrera-Chimal J, Garzón-Muvdi J, Pérez-Villalva R, Rodríguez-Romo R, Cruz C, et al. Recovery from ischemic acute kidney injury by spironolactone administration. Nephrol Dial Transplant. 2012;27:3160–9.CrossRefPubMed
51.
Barrera-Chimal J, Pérez-Villalva R, Ortega JA, Sánchez A, Rodríguez-Romo R, Durand M, et al. Mild ischemic injury leads to long-term alterations in the kidney: amelioration by spironolactone administration. Int J Biol Sci. 2015;11:892–900.CrossRefPubMedPubMedCentral
52.
Nguyen Dinh Cat A, Griol-Charhbili V, Loufrani L, Labat C, Benjamin L, Farman N, et al. The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure. FASEB J. 2010;24:2454–63.CrossRefPubMed
53.
Farman N, Vandewalle A, Bonvalet JP. Autoradiographic study of aldosterone and dexamethasone binding in isolated glomeruli of rabbit kidney. Am J Physiol. 1982;243:F235–42.PubMed
54.
Lee HA, Song MJ, Seok YM, Kang SH, Kim SY, Kim I. Histone deacetylase 3 and 4 complex stimulates the transcriptional activity of the mineralocorticoid receptor. PLoS ONE. 2015;10, e0136801.CrossRefPubMedPubMedCentral
55.
Shibata S, Nagase M, Yoshida S, Kawarazaki W, Kurihara H, Tanaka H, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008;14:1370–6.CrossRefPubMed
56.
Quinkler M, Zehnder D, Eardley KS, Lepenies J, Howie AJ, Hughes SV, et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation. 2005;112:1435–43.CrossRefPubMed
57.
Huang LL, Nikolic-Paterson DJ, Han Y, Ozols E, Ma FY, Young MJ, et al. Myeloid mineralocorticoid receptor activation contributes to progressive kidney disease. J Am Soc Nephrol. 2014;25:2231–40.CrossRefPubMedPubMedCentral
58.
Standards of medical care in diabetes 2014. Diabetes Care 2014;37 Suppl 1:S14-80
59.
Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol. 2007;3:486–92.CrossRefPubMed
60.
Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev 2009:CD007004.
61.
Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008;51:199–211.CrossRefPubMed
62.
Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med. 2001;345:925–6.CrossRefPubMed
63.
Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005;28:2106–12.CrossRefPubMed
64.
Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41:64–8.CrossRefPubMed
65.
Epstein M, Williams GH, Weinberger M, et al. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006;1:940–51.CrossRefPubMed
66.
Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014;4, CD007004.PubMed
67.
Schwenk MH, Hirsch JS, Bomback AS. Aldosterone blockade in CKD: emphasis on pharmacology. Adv Chronic Kidney Dis. 2015;22:123–32.CrossRefPubMed
68.
Vardeny O, Wu DH, Desai A, Rossignol P, Zannad F, Pitt B, et al. Influence of baseline and worsening renal function on efficacy of spironolactone in patients with severe heart failure: insights from RALES (Randomized Aldactone Evaluation Study). J Am Coll Cardiol. 2012;60:2082–9.CrossRefPubMed
69.
Rossignol P, Cleland JG, Bhandari S, Tala S, Gustafsson F, Fay R, et al. Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. Circulation. 2012;125:271–9.CrossRefPubMed
70.
Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–17.CrossRefPubMed
71.
Drechsler C, Ritz E, Tomaschitz A, Pilz S, Schönfeld S, Blouin K, et al. Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients. Eur Heart J. 2013;34:578–87.CrossRefPubMedPubMedCentral
72.
Matsumoto Y, Mori Y, Kageyama S, Arihara K, Sugiyama T, Ohmura H, et al. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol. 2014;63:528–36.CrossRefPubMed
73.
Menard J. The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004;217:45–52.CrossRefPubMed
74.
Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987;237:268–75.CrossRefPubMed
75.•
Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: Prospects for novel therapeutics. Mol Cell Endocrinol. 2012;350:310–7. This review provides an excellent overview of early non-steroidal development and rationale from an industry perspective.CrossRefPubMed
76.
Rossier BC, Baker ME, Studer RA. Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited. Physiol Rev. 2015;95:297–340.CrossRefPubMed
77.
Parthasarathy HK, Ménard J, White WB, Young Jr WF, Williams GH, Williams B, et al. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J Hypertens. 2011;29:980–90.CrossRefPubMed
78.
Netchitailo P, Delarue C, Perroteau I, Leboulenger F, Capron MH, Vaudry H. Relative inhibitory potency of five mineralocorticoid antagonists on aldosterone biosynthesis in vitro. Biochem Pharmacol. 1985;34:189–94.CrossRefPubMed
79.
Ye P, Yamashita T, Pollock DM, Sasano H, Rainey WE. Contrasting effects of eplerenone and spironolactone on adrenal cell steroidogenesis. Horm Metab Res. 2009;41:35–9.CrossRefPubMedPubMedCentral
80.
Penhoat A, Darbeida H, Bernier M, Saez JM, Durand P. Inhibition of hormonal-induced cAMP and steroid production by inhibitors of pregnenolone metabolism in adrenal and Leydig cells. Mol Cell Endocrinol. 1988;60:55–60.CrossRefPubMed
81.
Albert NM, Yancy CW, Liang L, Zhao X, Hernandez AF, Peterson ED, et al. Use of aldosterone antagonists in heart failure. JAMA. 2009;302:1658–65.CrossRefPubMed
82.
Amazit L, Le Billan F, Kolkhof P, Lamribet K, Viengchareun S, Fay MR, et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. J Biol Chem. 2015;290(36):21876–89.CrossRefPubMed
83.
Bärfacker L, Kuhl A, Hillisch A, Grosser R, Figueroa-Pérez S, Heckroth H, et al. Kolkhof P Discovery of BAY 94–8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7(8):1385–403.CrossRefPubMed
84.
Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist bay 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: A randomized, double-blind trial. Eur Heart J. 2013;34:2453–63.CrossRefPubMedPubMedCentral
85.
Pitt B, Filippatos G, Gheorghiade M, et al. Rationale and design of arts: A randomized, double-blind study of bay 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail. 2012;14:668–75.CrossRefPubMed
86.••
Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92. This publication is the first to demonstrate effectiveness of non-steroidal MR antagonists in humans.CrossRefPubMed
87.
Ruilope LM, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. Rationale, design, and baseline characteristics of ARTS-DN: a randomized study to assess the safety and efficacy of finerenone in patients with type 2 diabetes mellitus and a clinical diagnosis of diabetic nephropathy. Am J Nephrol. 2014;40:572–81.CrossRefPubMed
88.••
Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314:884–94. First study to demonstrate anti-proteinuric effects of finererone in diabetic patients with nephropathy.CrossRefPubMed
89.
Mavrakanas TA, Gariani K, Martin PY. Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in diabetic nephropathy. Eur J Int Med. 2014;25(2):173–6.CrossRef
90.
Mehdi UF, Adams-Huet B, Raskin P, et al. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. J Am Soc Nephrol. 2009;20(12):2641–50.CrossRefPubMedPubMedCentral
Metadaten
Titel
Finerenone: a New Mineralocorticoid Receptor Antagonist Without Hyperkalemia: an Opportunity in Patients with CKD?
verfasst von
Hermann Haller
Anna Bertram
Klaus Stahl
Jan Menne
Publikationsdatum
01.04.2016
Verlag
Springer US
Erschienen in
Current Hypertension Reports / Ausgabe 5/2016
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-016-0649-2

Weitere Artikel der Ausgabe 5/2016

Current Hypertension Reports 5/2016 Zur Ausgabe

Blood Pressure Monitoring and Management (J Cockcroft, Section Editor)

Hypertension in the Emergency Department

Resistant Hypertension (E Pimenta, Section Editor)

Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison

Novel Treatments for Hypertension (T Unger, Section Editor)

Multifactorial Prevention of Cardiovascular Disease in Patients with Hypertension: the Cardiovascular Polypill

Pulmonary Hypertension (JR Klinger, Section Editor)

Soluble Guanylate Cyclase Stimulators and Activators: Novel Therapies for Pulmonary Vascular Disease or a Different Method of Increasing cGMP?

Hypertension and the Kidney (RM Carey, Section Editor)

New Evidence Supporting the Use of Mineralocorticoid Receptor Blockers in Drug-Resistant Hypertension

Hypertension and the Kidney (RM Carey, Section Editor)

Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise