(Alte) Neue Medikamente: Aldosteron-Antagonisten zur Behandlung kardiovaskulärer und nephrologischer Erkrankungen

Summary

Aldosterone antagonists are established in the heart failure therapy armamentarium. Several randomized controlled trials have rendered compelling data for their application. Clinical studies also suggest that aldosterone antagonists can reduce proteinuria in patients with diabetic nephropathy and may be nephroprotective. However, recent studies also show that the incidence of life-threatening hyperkalemia has increased sharply since the publication of the heart failure trials. Physicians prescribing these drugs must be familiar with the physiology of potassium excretion in the distal neprhon. In this report we briefly review the physiology of aldosterone, data from clinical trials, and discuss the avoidance of life-threatening hyperkalemia.

Literatur

• 1 The SOLVD Investigators . Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.  N Engl J Med. 1991;  325 293-302
• 2 K/DOQI . Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification.  Am J Kidn Dis. 2002;  39 S76-S110
• 3 Aznar J, Estelles A. Role of plasminogen activator inhibitor type 1 in the pathogenesis of coronary artery diseases.  Haemostasis. 1994;  24 243-251
• 4 Brilla C G, Zhou G, Matsubara L, Weber K T. Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone.  J Mol Cell Cardiol. 1994;  26 809-820
• 5 Brown N J, Vaughan D E, Fogo A B. Aldosterone and PAI-1: implications for renal injury.  J Nephrol. 2002;  15 230-235
• 6 Chander P N, Rocha R, Ranaudo J, Singh G, Zuckerman A, Stier C T. Aldosterone plays a pivotal role in the pathogenesis of thrombotic microangiopathy in SHRSP.  J Am Soc Nephrol. 2003;  14 1990-1997
• 7 De Gasparo M, Joss U, Ramjoue H P. et al . Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro.  J Pharmacol Exp Ther. 1987;  240 650-656
• 8 Epstein M, Buckalew V, Martinez F. et al . Antiproteinuric efficacy of eplerenone, enalapril and eplerenone/enalapril combination in diabetic hypertensives with microalbuminuria.  Am J Hypertension. 2002;  15 24A
• 9 Farquharson C A, Struthers A D. Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy.  Clin Sci (Lond). 2002;  103 425-431
• 10 Farquharson C A, Struthers A D. Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure.  Circulation. 2000;  101 594-597
• 11 Fitzgibbon W R, Greene E L, Grewal J S. et al . Resistance to remnant nephropathy in the Wistar-Furth rat.  J Am Soc Nephrol. 1999;  10 814-821
• 12 Funder J W, Feldman D, Edelman I S. Specific aldosterone binding in rat kidney and parotid.  J Steroid Biochem. 1972;  3 209-218
• 13 Hene R J, Boer P, Koomans H A, Mees E J. Plasma aldosterone concentrations in chronic renal disease.  Kidney Int. 1982;  21 98-101
• 14 Juurlink D N, Mamdani M M, Lee D S. et al . Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.  N Engl J Med. 2004;  351 543-551
• 15 Lakkis J, Lu W X, Weir M R. RAAS escape: a real clinical entity that may be important in the progression of cardiovascular and renal disease.  Curr Hypertens Rep. 2003;  5 408-417
• 16 Lewis E J, Hunsicker L G, Bain R P, Rohde R D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group.  N Engl J Med. 1993;  329 1456-1462
• 17 Mazak I, Fiebeler A, Muller D N. et al . Aldosterone potentiates angiotensin II-induced signaling in vascular smooth muscle cells.  Circulation. 2004;  109 2792-2800
• 18 Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.  Lancet. 2003;  361 117-124
• 19 Neumann S, Huse K, Semrau R. et al . Aldosterone and D-glucose stimulate the proliferation of human cardiac myofibroblasts in vitro.  Hypertension. 2002;  39 756-760
• 20 Palmer B F. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system.  N Engl J Med. 2004;  351 585-592
• 21 Pitt B, Remme W, Zannad F. et al . Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.  N Engl J Med. 2003;  348 1309-1321
• 22 Pitt B, Zannad F, Remme W J. 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;  341 709-717
• 23 Pratt J H, Peacock M, Henry D P. Effect of recombinant human growth hormone on adreno-cortical function, and on sodium and potassium homeostasis.  Pharmacology. 1993;  47 36-42
• 24 Quan Z Y, Walser M, Hill G S. Adrenalectomy ameliorates ablative nephropathy in the rat independently of corticosterone maintenance level.  Kidney Int. 1992;  41 326-333
• 25 Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy.  Hypertension. 2003;  41 64-68
• 26 Sato A, Saruta T. Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in essential hypertensive patients with left ventricular hypertrophy.  J Int Med Res. 2001;  29 13-21
• 27 Satoh M, Nakamura M, Saitoh H. et al . Aldosterone synthase (CYP11B2) expression and myocardial fibrosis in the failing human heart.  Clin Sci (Lond). 2002;  102 381-386
• 28 Selye H. Protection by a steroid-spirolactone against certain types of cardiac necroses.  Proc Soc Exp Biol Med. 1960;  104 212-213
• 29 Simpson S A, Tait J F, Wettstein A, Neher R, Von Euw J, Reichstein T. Isolation from the adrenals of a new crystalline hormone with especially high effectiveness on mineral metabolism.  Experientia. 1953;  9 333-335
• 30 Stabroth C, Toka H, Krupp G, Muller V, Luft F C. Serendipitous prophylactic pacemaker treatment for hyperkalemia.  Am J Med. 1999;  106 123-124
• 31 Sturtevant F M. Prevention by adrenal-regeneration hypertension by an aldosterone-blocker.  Endocrinology. 1959;  64 299-300
• 32 Tsybouleva N, Zhang L, Chen S. et al . Aldosterone, through novel signaling proteins, is a fundamental molecular bridge between the genetic defect and the cardiac phenotype of hypertrophic cardiomyopathy.  Circulation. 2004;  109 1284-1291
• 33 Walker W G. Hypertension-related renal injury: a major contributor to end-stage renal disease.  Am J Kidney Dis. 1993;  22 164-173