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Vol 23, No 1 (2019)
REVIEW
Published online: 2018-10-08
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The role of aldosterone in kidney diseases and hypertension. Is it worth using mineralocorticoid receptor antagonists in clinical practice?
1, 1
Affiliations- Department of Nephrology, Hypertension and Internal Medicine, Collegium Medicum, Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland
open access
Vol 23, No 1 (2019)
REVIEW
Published online: 2018-10-08
Abstract
Aldosterone is a mineralocorticoid hormone which plays a pivotal role in water and electrolytes balance. Moreover,
aldosterone exerts a deleterious influence on the cardiovascular system and kidneys. In this review, we wanted to
show mechanisms of aldosterone related organ damage, the role of aldosterone in kidney diseases, hypertension and
therapeutic benefits related with aldosterone receptors blockade.
Abstract
Aldosterone is a mineralocorticoid hormone which plays a pivotal role in water and electrolytes balance. Moreover,
aldosterone exerts a deleterious influence on the cardiovascular system and kidneys. In this review, we wanted to
show mechanisms of aldosterone related organ damage, the role of aldosterone in kidney diseases, hypertension and
therapeutic benefits related with aldosterone receptors blockade.
Get Citation
Keywords
aldosterone; chronic kidney disease; hypertension; cardiovascular risk, aldosterone antagonists
About this articleTitle
The role of aldosterone in kidney diseases and hypertension. Is it worth using mineralocorticoid receptor antagonists in clinical practice?
Journal
Issue
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1-7
Published online
2018-10-08
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DOI
Bibliographic record
Arterial Hypertension 2019;23(1):1-7.
Keywords
aldosterone
chronic kidney disease
hypertension
cardiovascular risk
aldosterone antagonists
Authors
Rafał Łukasz Donderski
Jacek Manitius
References (53)- Weber KT, Villarreal D. Aldosterone and antialdosterone therapy in congestive heart failure. Am J Cardiol. 1993; 71(3): 3A–11A.
- Hollenberg NK. Aldosterone in the development and progression of renal injury. Kidney Int. 2004; 66(1): 1–9.
- Epstein M. Aldosterone as a determinant of cardiovascular and renal dysfunction. J R Soc Med. 2001; 94(8): 378–383.
- 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(10): 709–717.
- Ferreira JP, Duarte K, McMurray JJV, et al. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348(14): 1309–1321.
- Musso CG. Potassium metabolism in patients with chronic kidney disease (CKD), Part I: patients not on dialysis (stages 3–4). Int Urol Nephrol. 2004; 36(3): 465–468.
- Funder JW. Aldosterone and Mineralocorticoid Receptors — Physiology and Pathophysiology. Int J Mol Sci. 2017; 18(5): 1032.
- Lindner A, Charra B, Sherrard DJ, et al. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med. 1974; 290(13): 697–701.
- Lai S, Dimko M, Galani A, et al. Early markers of cardiovascular risk in chronic kidney disease. Ren Fail. 2014; 37(2): 254–261.
- Funder J. Mineralocorticoids and cardiac fibrosis: the decade in review. Clin Exp Pharmacol Physiol. 2001; 28(12): 1002–1006.
- Sato A, Funder JW. High glucose stimulates aldosteron-induced hyperthrophy via type I mineralocorticoid receptors in neonatal rat cardiomiocytes. Endocrinology. 1996; 137(10): 4145–4153.
- Feniman De Stefano GM, Zanati-Basan SG, De Stefano LM, et al. Aldosterone is associated with left ventricular hypertrophy in hemodialysis patients. Ther Adv Cardiovasc Dis. 2016; 10(5): 304–313.
- Abiose AK, Mansoor GA, Barry M, et al. Effect of spironolactone on endothelial function in patients with congestive heart failure on conventional medical therapy. Am J Cardiol. 2004; 93(12): 1564–1566.
- Leibovitz E, Ebrahimian T, Paradis P, et al. Aldosterone induces arterial stiffness in absence of oxidative stress and endothelial dysfunction. J Hypertens. 2009; 27(11): 2192–2200.
- Miller AB. Aldosterone antagonism in heart failure. Vasc Health Risk Manag. 2007; 3(5): 605–609.
- Gilbert KC, Brown NJ. Aldosterone and inflammation. Curr Opin Endocrinol Diabetes Obes. 2010; 17(3): 199–204.
- Currie G, Taylor AHM, Fujita T, et al. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol. 2016; 17(1): 127.
- Kato S, Maruyama S, Makino H, et al. Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: a multicenter, randomized clinical trial. Clin Exp Nephrol. 2015; 19(6): 1098–1106.
- Wildling L, Hinterdorfer P, Kusche-Vihrog K, et al. Aldosterone receptor sites on plasma membrane of human vascular endothelium detected by a mechanical nanosensor. Pflugers Arch. 2008; 458(2): 223–230.
- Toto RD. Aldosterone blockade in chronic kidney disease: can it improve outcome? Curr Opin Nephrol Hypertens. 2010; 19(5): 444–449.
- Quinkler M, Zehnder D, Eardley KS, et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation. 2005; 112(10): 1435–1443.
- Shibata S, Fujita T. Mineralocorticoid receptors in the pathophysiology of chronic kidney diseases and the metabolic syndrome. Mol Cell Endocrinol. 2012; 350(2): 273–280.
- Shibata S, Ishizawa K, Uchida S. Mineralocorticoid receptor as a therapeutic target in chronic kidney disease and hypertension. Hypertens Res. 2017; 40(3): 221–225.
- Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006; 70(12): 2116–2123.
- Ma TW, Szeto CC. Mineralocorticoid Receptor Antagonist for Renal Protection. Ren Fail. 2012; 34(6): 810–817.
- Tylicki L, Lizakowski S, Rutkowski P, et al. The enhanced renin-angiotensin-aldosteron system pharmacological blockade — which is the best?. Kidney Blood Press Res. 2012; 36(1): 335–343.
- Struthers AD. The clinical implications of aldosterone escape in congestive heart failure. Eur J Heart Fail. 2004; 6(5): 539–545.
- Sato A, Sato A, Saruta T, et al. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003; 41(1): 64–68.
- Dutzmann J, Musmann RJ, Haertlé M, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS One. 2017; 12(9): e0184888.
- Sun LJ, Sun YN, Shan JP, et al. Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy. J Diabetes Investig. 2017; 8(4): 609–618.
- Edwards NC, Steeds RP, Stewart PM, et al. Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial. J Am Coll Cardiol. 2009; 54(6): 505–512.
- Hill N, Lasserson D, Thompson B, et al. Benefits of Aldosterone Receptor Antagonism in Chronic Kidney Disease (BARACK D) trial–a multi-centre, prospective, randomised, open, blinded end-point, 36-month study of 2,616 patients within primary care with stage 3b chronic kidney disease to compare the efficacy of spironolactone 25 mg once daily in addition to routine care on mortality and cardiovascular outcomes versus routine care alone: study protocol for a randomized controlled trial. Trials. 2014; 15: 160.
- Weir MR, Bakris GL, Bushinsky DA, et al. OPAL-HK Investigators. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015; 372(3): 211–221.
- Covic A, Gusbeth-Tatomir P, Goldsmith DJA. Is it time for spironolactone therapy in dialysis patients? Nephrol Dial Transplant. 2006; 21(4): 854–858.
- Nitta K, Akiba T, Nihei H. Aldosterone blockade and vascular calcification in hemodialysis patients. Am J Med. 2003; 115(3): 250a.
- Donderski R, Stróżecki P, Sulikowska B, et al. Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients. Int Urol Nephrol. 2017; 49(10): 1867–1873.
- Vukusich A, Kunstmann S, Varela C, et al. A randomized, double-blind, placebo-controlled trial of spironolactone on carotid intima — media thickness in nondiabetic hemodialysis patients. Clin J Am Soc Nephrol. 2010; 5(8): 1380–1387.
- Khai PNg, Jain P, Heer G, et al. Spironolactone to prevent cardiovascular events in early-stage chronic kidney disease (STOP-CKD): study protocol for a randomized controlled pilot trial. Trials. 2014; 15: 158.
- Chua D, Lo A, Lo C. Spironolactone use in heart failure patients with end-stage renal disease on hemodialysis: is it safe? Clin Cardiol. 2010; 33(10): 604–608.
- Matsumoto Y, Mori Y, Kageyama S, et al. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol. 2014; 63(6): 528–536.
- Bomback AS. Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease: Efficacy and Safety. Blood Purif. 2016; 41(1–3): 166–170.
- Fenwick S, Bell GM. Aldactone therapy in a peritoneal dialysis patient. Nephrol Dial Transplant. 2003; 18(6): 1232–1232.
- Hausmann MJ, Liel-Cohen N. Aldactone therapy in a peritoneal dialysis patient with decreased left ventricular function. NDT. 2002; 17(11): 2035–2036.
- Ito Y, Mizuno M, Suzuki Y, et al. Nagoya Spiro Study Group. Long-term effects of spironolactone in peritoneal dialysis patients. J Am Soc Nephrol. 2014; 25(5): 1094–1102.
- Kolesnyk I, Noordzij M, Dekker FW, et al. A positive effect of AII inhibitors on peritoneal membrane function in long-term PD patients. Nephrol Dial Transplant. 2009; 24(1): 272–277.
- Vazquez-Rangel A, Soto V, Escalona M, et al. Spironolactone to prevent peritoneal fibrosis in peritoneal dialysis patients: a randomized controlled trial. Am J Kidney Dis. 2014; 63(6): 1072–1074.
- Siewaszewicz E. Antagoniści aldosteronu w leczeniu nadciśnienia tętniczego. AHT. 2010; 14(3): 216–226.
- Yugar-Toledo JC, Modolo R, Moreno H, et al. Managing resistant hypertension: focus on mineralocorticoid-receptor antagonists. Vasc Health Risk Manag. 2017; 13: 403–411.
- Dahal K, Kunwar S, Rijal J, et al. The Effects of Aldosterone Antagonists in Patients With Resistant Hypertension: A Meta-Analysis of Randomized and Nonrandomized Studies. Am J Hypertens. 2015; 28(11): 1376–1385.
- Goodfriend TL, Ball DL, Egan BM, et al. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension. 2004; 43(2): 358–363.
- Tomaschitz A, Ritz E, Pieske B, et al. Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease. Cardiovasc Res. 2012; 94(1): 10–19.
- Williams B, MacDonald TM, Morant S, et al. British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015; 386(10008): 2059–2068.
- Bolignano D, Palmer SC, Navaneethan SD, et al. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014(4): CD007004.